Targeting B Cells for the Treatment of Idiopathic Inflammatory Myopathy.

Introduction

Idiopathic inflammatory myopathy (IIM) is a group of heterogeneous diseases characterized by typical rashes, symmetric proximal muscle weakness, and interstitial lung changes. The pathogenesis of IIM involves the activation of various immune cell types, with B cells producing autoantibodies playing a crucial role. Within IIM, there are myositis-specific antibodies and myositis-associated antibodies. There is a trend to classify IIM into different clinical subtypes based on these autoantibodies [ 1 , 2 ]. Additionally, B cells play a pivotal role in the pathogenesis of IIM by activating other immune cells such as T cells, dendritic cells, and macrophages through the secretion of cytokines and immunoregulatory factors. Therapeutic strategies targeting B cells and their activation factors are increasingly becoming integral to the treatment of IIM. This review aims to summarize the current understanding of the role of B cells in IIM and the associated therapeutic approaches. It discusses ongoing clinical trials supporting B cell-targeted therapies and evaluates their efficacy, safety, and potential in managing IIM, with the goal of improving patient outcomes.(Table 1 and Fig. 1 ). Table 1 Advances in clinical research on B cell-targeted therapy in the field of idiopathic inflammatory myopathies Reference Target Drug name Study design Diagnosis Number of patients Remarks Primary endpoint Outcome/prognosis Overview Lung Muscle G. Y. Ahn [ 3 ] CD20 Rituximab Retrospective Refractory IIM 16 Refractory cases Improvement: a significant improvement is a > 25% decrease in CPK levels, corticosteroid dose, or PGA. Complete response (CR) requires meeting all three criteria, while partial response (PR) requires two After 24 weeks of RTX treatment, 9 of 16 showed improved PGA, with a 68.8% overall response rate. At follow-up, 75% of patients responded, with 25% achieving CR and 50% achieving PR / Post-RTX, 11 of 16 patients had a > 25% CPK reduction Abhilasha Manwatkar [ 4 ] CD20 Rituximab Observational study IIM (19DM,22PM,17NM,2ADM,13OM) 60 33 (55%) were ‘treatment-naïve’ IIM and 27(45%) were ‘refractory’ cases Improvement: Muscularly, ≥ 20% MMT8/MRC score boost from baseline to 6 months and final follow-up marks improvement. Extramuscularly, TJC, SJC, spirometry, PtGA, PGA, and skin changes from baseline to 6 months and last follow-up are considered At 6 months of follow-up, 48/55 (87%) patients satisfied the outcome measure of improvement which included 31/31 (100%) in the ‘treatment-naïve’ and 17/24 (70%) in the ‘refractory’ group / MMT8 Score Changes :Treatment-Naïve Group: Mean change of 13.41 (S.D. 7.31); Refractory Group: Mean change of 8.33 (S.D. 7.92), P = 0.017 Corrado Campochiaro [ 5 ] CD20 Rituximab Retrospective IIM 20 Refractory cases 2016 ACR/EULAR criteria for minimal, moderate, and major clinical response for IIM Moderate or major response was observed in all patients / From T0 to T12, there was significant improvement in all IMACS core measures. The MYOACT score dropped from 0.245 to 0.07, the MMT8 score rose from 77 to 80 I. Marie [ 6 ] CD20 Rituximab Retrospective case series ASyS 7 Refractory cases Resolution is total pulmonary symptom disappearance, ILD radiographic sign vanishing, and PFT value normalization. Improvement is any pulmonary change betterment without reaching normal, with ≥ 10% FVC or ≥ 15% DLCO increase significant. Deterioration is any pulmonary aspect worsening during treatment, ≥ 10% FVC or ≥ 15% DLCO decrease being notable FVC and DLCO increased significantly, with medians at 74% and 59%; HRCT showed improved ILD abnormalities in 5 patients; no progression in 2; Median prednisone dose reduced from 20 to 9 mg daily FVC and DLCO increased significantly, with medians at 74% and 59%; HRCT showed improved ILD abnormalities in 5 patients; / Doyle [ 7 ] CD20 Rituximab Case series ASyS 25 21 Refractory cases Improvement: CT severity scores was defined as a ≥ 10% decrease while improvement in PFTs was defined as a ≥ 10% increase in FVC. Stability in CT score was defined as a ≤ 10% increase while PFT stability was defined as a ≤ 10% decrease in FVC Pulmonary function improved in 88% of patients, with significant FVC and DLCO increases over 3 years. Prednisone dosage was reduced in 88% of patients. HRCT scans showed improvement in 36%, stability in 57%, and worsening in 7% of patients Pulmonary function improved in 88% of patients, with significant FVC and DLCO increases over 3 years. HRCT scans showed improvement in 36%, stability in 57%, and worsening in 7% of patients / Andersson [ 8 ] CD20 Rituximab Retrospective ASyS 34 / FVC, FEV1, DLCO per ATS standards; HRCT quantifies ILD extent in lung parenchyma, myositis evaluated by plasma CK, MMT8 FVC, FEV1, DLCO increased by 24%, 22%, 17%; ILD reduced from 50 to 33% in lungs; CK dropped to 88 U/L; MMT8 rose to 98% FVC, FEV1, DLCO increased by 24%, 22%, 17%; ILD reduced from 50 to 33% in lungs; CK dropped to 88 U/L; MMT8 rose to 98% H. So [ 9 ] CD 20 Rituximab Retrospective ADM (MDA5 +) 4 Refractory cases NYHA dyspnea classification, oxygen therapy requirements, PFT and CT Improving respiratory symptoms, pulmonary function, and radiological manifestations improving respiratory symptoms, pulmonary function, and radiological manifestations / M. M. Mao [ 10 ] CD 20 Rituximab Retrospective DM(MDA5 +) 40 / 180-day mortality were measured by Cox regression analysis Non-significant trend towards reduced 180-day mortality in the group receiving RTX with/without CTX / / Javier Narváez [ 11 ] CD 20 Rituximab Multicenter observational retrospective ASyS 28 / Key outcomes are changes in % pFVC, % pDLCO, 6MWT distance, and HRCT after RTX treatment % pFVC and % pDLCO increasing by 6.29% and 6.15% at 6 months, and 11.63% and 10.29% at 1 year. HRCT showed stabilization or improvement in 92% and 88% of patients at 6 and 12 months % pFVC and % pDLCO increasing by 6.29% and 6.15% at 6 months, and 11.63% and 10.29% at 1 year.HRCT showed stabilization or improvement in 92% and 88% of patients at 6 and 12 months / T. M. Maher [ 12 ] CD20 Rituximab RCT IIM 44 / Primary endpoint: 24-week FVC change. Secondary endpoints: 48-week FVC change and others Rituximab not superior to cyclophosphamide in CTD-ILD, yet both improved lung function and QoL, with rituximab causing fewer adverse events and less steroid use / / Oddis, C.V [ 13 ] CD20 Rituximab RCT IIM 236 200 refractory cases Primary Endpoint: Time to achieve the definition of improvement; Secondary Endpoints Time to ≥ 20% improvement in muscle strength; Proportion achieving DOI at week 8 83% of patients achieved the definition of improvement by week 44 / No significant difference in time to ≥ 20% MMT-8 improvement M. T. Holzer [ 14 ] CD38 Daratumumab Case report DM (MDA5 +) 1 Refractory cases / Improve pulmonary CT scan shows significant improvement / L. Ostendorf [ 15 ] CD38 Daratumumab Case report DM(MDA5 +) 1 Refractory cases / Improve pulmonary CT scan shows significant improvement / O. Landon-Cardinal [ 16 ] CD38 Daratumumab Case report IMNM(SRP +) 1 Refractory cases / Improve / Quantitative muscle strength significantly improved (hand grip from 5.1 to 19 kg, quadriceps from 56 to 121 kg), parenteral nutrition was discontinued, respiratory assistance was weaned, and CK level decreased to < 1000 IU/L from 6000 IU/L Pecher, A.C [ 17 ] CD19 CAR-T Case report ASyS(Jo-1 +) 1 Refractory case / Improve Pulmonary function tests improved MRI of thigh muscle showed no detectable signs of myositis. Functional muscle tests and serological muscle enzymes improved Muller, F. [ 18 ] CD19 CAR-T Case report ASyS(Jo-1 +) 1 Refractory case / Improve Respiratory symptoms improved; no oxygen supplementation needed.Chest CT showed full regression of alveolitis MMT score: 115/150 → 149/150; Holding 1.3 kg bottle: 5 s → 33 s; Walking distance: 10 m → > 5 km; Creatine kinase: 13,600 U/L → 102 U/L; Myoglobin: 2,148 µg/L → 70 µg/L Taubmann, J.[ 19 ] CD19 CAR-T Case report ASyS(Jo-1 +) 1 Refractory case / Improve significant reduction in mesenchymal tissue activation observed on PET-CT scans MMT score: 103/150 → 149/150; Holding 1.3 kg bottle: 10 s → 61 s; Walking distance: 50 m → > 2 km; Creatine kinase: 4298 U/L → 99U/L; Myoglobin: 2945 µg/L → 53 µg/L Chuan Qin [ 20 ] BCMA CAR-T Case report SRP + IMNM 1 Refractory case / Improve / Upper limb strength: Regained ability to lift arms; Lower limb strength: Regained ability to walk;MMT-8 score: 96 → 137;CK: 4,778 IU/L → 260 IU/L; Myoglobin: 837 ng/mL → 66.2 ng/mL.;MRI: Reduced active muscle lesions in arms and thighs X. Wang [ 21 ] CD19 CAR-T Case report SRP + IMNM 1 Refractory case / Improve / Upper limb strength improved, enabling arm lifting without limitations; MMT-8 score: 96 → 137; CK levels: 9,536 U/L → 3,700 U/L; MRI: Reduced active muscle lesions in arms and thighs at 18-month follow-up B. B. Cui [ 22 ] BAFF Belimumab case report IMNM 1 / Improve / CK levels: 1073U/L → 119U/L; MYOACT Score:6.2/60 → 1.9/60 G. Marder [ 23 ] BAFF Belimumab RCT IIM 17 / DOI and TIS By week 40, belimumab patients had a higher DOI rate (33.3%) than placebo (16.7%), but this was not significant at week 64. In the belimumab group, 55.5% met TIS ≥ 40 at week 40, and 44.7% at week 64, with no significant differences in core set measures between groups / / Y. Liu [ 24 ] BAFF Belimumab Retrospective DM, JDM 13(DM 6, JDM 7) / Primary endpoint: ≥ 20% decrease in MITAX score by week 12 12 patients (6 adult DM and 6 JDM) achieved the primary outcome, with MITAX scores dropping significantly from baseline and maintaining clinical stability for 24 weeks / / H. Gao [ 25 ] BAFF/ APRIL Telitacicept Retrospective observational study IIM 11(9IMNM,1PM,1DM) Refractory case Total Improvement Score (TIS), based on the 2016 ACR/ EULAR consensus criteria for myositis; Minimal, moderate and major improvements are defined by TIS thresholds of ≥ 20, ≥ 40 and ≥ 60 points, respectively 90.91%responded well, with 6 showing significant, 4 moderate, and 1 mild improvement. Average prednisone dose dropped from 27.05 mg to 12.05 mg / / M. Hagen [ 26 ] BiTE Teclistamab Case report MDA5 + 1 Refractory case / Improve DCLOSB: 138 → 157 MMT8 score:138 → 150 M. Yang [ 27 ] Anti-Fcrn Efgartigimod Open-label pilot observational study 5HMCGR + ; 2SRP + 7 Refractory case Total Improvement Score (TIS), based on the 2016 ACR/ EULAR consensus criteria for myositis 4 out of 7 patients achieved clinical responses / / Fig. 1 Potential target molecules in B Cells for the treatment of idiopathic inflammatory myopathies (IIM). B cells play a crucial role in the disease pathology via multiple mechanisms, including cytokine secretion, cell-to-cell interactions, antigen presentation, and autoantibody generation. therapies that target B cells, such as inhibitors of BAFF, APRIL, CD19, CD20, CD38, and FcRn, hold the promise of alleviating the symptoms associated with IIM. BAFF, B cell activating factor; APRIL, a proliferation inducing ligand; FcRn, neonatal Fc receptor

B Cells and IIM: Depletion Therapy Insights

B cells at various differentiation stages are evident in muscle pathology across myositis subtypes, including polymyositis, dermatomyositis (DM), inclusion body myositis (IBM), and antisynthetase syndrome (ASyS) [ 28 ]. B cell-derived antibodies can damage muscle cells by directly activating the interferon pathway (e.g., anti-MDA5) or disrupting enzyme functions (e.g., anti-Jo-1 targeting histidyl-tRNA synthetase) [ 29 ]. Anti-SRP and anti-HMGCR antibodies have been shown to induce muscle fiber atrophy and impair muscle regeneration, actively contributing to the muscular dysfunction observed in immune-mediated necrotizing myopathy (IMNM) [ 30 ]. The detection of B cell receptor clones in muscle tissue corresponds to their presence in peripheral blood, highlighting the trafficking of peripheral B cells to tissues [ 31 ]. Single cell sequencing analyses of peripheral blood and lung tissues from MDA5 + DM patients have revealed a notable increase in diverse B cell subtypes [ 32 , 33 ]. These antibodies also form immune complexes with self-antigens, which deposit in tissues and activate the complement system, amplifying inflammation, as seen with anti-SRP and anti-HMGCR antibodies [ 34 ]. B cells sustain their survival and antibody production via cytokines like B cell activating factor (BAFF) and a proliferation inducing ligand (APRIL), which are upregulated in the muscle microenvironment. These factors also collaborate with macrophages to orchestrate disease pathogenesis [ 35 ]. Enhanced expression of endoplasmic reticulum stress and oxidative phosphorylation-related genes within B cells in idiopathic inflammatory myopathies (IIMs) indicates significant activation of B cells that correlates with disease activity [ 36 ]. Furthermore, B cells contribute to myositis pathogenesis by secreting cytokines and interacting with other immune cells to modulate immune responses. B cells engage with T cells via CD40/CD40L and cytokines (IL-6 and TNF-α), driving germinal center-like reactions that promote autoantibody affinity maturation and exacerbate muscle inflammation and chronic damage [ 37 ]. Collectively, these findings underscore the potential of B cell depletion as a therapeutic strategy for IIMs.

B Cell Depletion in Clinical Therapy

CD20

CD20, a B cell marker present throughout development from precursor to memory B cells but not expressed on plasmablasts and plasma cells, is targeted by rituximab. Numerous studies have indicated the efficacy of CD20 in treating IIMs, with comprehensive reviews available [ 38 ]. This summary focuses on refractory IIMs and IIM-associated interstitial lung disease (IIM-ILD).

In a retrospective study of 16 patients with relapsing/refractory IIM by Ahn et al. [ 3 ], all on corticosteroids and at least one immunosuppressive agent, rituximab (RTX) treatment for 24 weeks resulted in over 25% reduction in steroid and CK levels in 11 patients and improved PGA in 9. The response rate was 68.8%, with 75% achieving favorable overall response by follow-up end, including 4 with complete remission and 8 with partial remission. Abhilasha et al.’s [ 4 ] prospective study of 60 IIM patients, including 33 treatment-naïve and 27 refractories, treating by RTX, showed an 87% treatment response at 6 months (100% in treatment-naïve and 70% in refractory) and reduced steroid use. No significant adverse events were reported over 24 months. Corrado et al.’s [ 5 ] study of 20 refractory IIM patients treated with RTX and mycophenolate mofetil (MMF) for 12 months showed moderate or major responses in all, with reduced CK levels and improvements in cardiac imaging, enzyme levels, and pulmonary function (FVC and DLCO). Corticosteroid dosage decreased from 8.75 to 0 mg, with 40% of patients off steroids by study’s end. Ten adverse events were reported, including upper respiratory tract infections, urinary tract infections, gastroenteritis, and herpes simplex virus infections. In the RIM study [ 13 ], 161 of 195 patients (83%) with refractory myositis achieved the definition of improvement by week 44, suggesting a potential therapeutic effect of rituximab in this refractory patient population. However, there was no significant difference between early and late administration of rituximab. Although the study demonstrates positive outcomes, it highlights a significant risk of infectious complications. These studies demonstrates that RTX is both effective and relatively safe for the treatment of refractory IIM. However, additional prospective randomized controlled trials (RCTs) are necessary to further substantiate the efficacy of RTX in IIM.

In the treatment of IIM-ILD, the 2023 ACR guidelines have highlighted the significance of rituximab, particularly in MDA5 + DM [ 39 ]. Marie et al. [ 6 ] retrospectively included 7 patients with anti-synthetase syndrome-related interstitial lung disease (ASS-ILD) treated with RTX, with follow-up at 6 and 12 months. The use of RTX improved respiratory symptoms, pulmonary function, and lung imaging changes. Doyle et al. [ 7 ] retrospectively included 25 patients with ASS-ILD, of which 21 refractory ILD patients were treated with RTX for an observation period of 1 year. A total of 88% of patients maintained stable CT scores and lung function, while 79% showed improvements, with FVC% increasing from 56 ± 13 to 64 ± 13. DLCO% initially dropped from 42 ± 17 to 36 ± 16 but recovered to 70 ± 20 by the third year. No major adverse events were reported during the 24-month follow-up. In a long-term study by Andersson et al. [ 8 ], 34 ASS-ILD patients treated with RTX for a median of 52 months showed improvements in FVC (24%), FEV1 (22%), and DLco (17%). Six of seven deaths were due to infections, mostly in patients with disease duration under 12 months or during acute exacerbations, who had better responses to RTX. So et al. [ 9 ] retrospectively analyzed four patients with amyopathic DM and acute progressive interstitial pneumonia unresponsive to high-dose corticosteroids and immunosuppressants; their lung function and chest imaging improved significantly after RTX treatment. Subsequently, Mao et al. [ 10 ] retrospectively included 40 MDA5-positive DM patients, divided into three groups: non-cyclophosphamide/RTX (CTX/RTX) ( n = 10), CTX alone ( n = 19), and RTX with or without CTX ( n = 11). RTX was administered at a dose of 100 mg, at least once, on top of other immunosuppressants. The results indicated that the survival rate at three months was higher in the RTX with or without CTX group compared to the other two groups, although the difference was not statistically significant, suggesting a trend towards reduced mortality with RTX as an “add-on therapy.” The RECITAL [ 12 ] study also confirmed that RTX can be a treatment option for severe or acutely progressive connective tissue disease-related ILD (including 44 cases of IIM), with efficacy comparable to CTX but with fewer side effects. A recent systematic review and meta-analysis [ 40 ] included 26 studies evaluating the efficacy and safety of rituximab (RTX) in the treatment of IIM. The results indicated that RTX was effective in 65% of patients, with 45% achieving a complete response and 39% a partial response. Subgroup analysis revealed overall response rates of 62%, 68%, and 62% for refractory IIM, DM, and polymyositis, respectively, and 59%, 65%, and 81% for muscle, lung, and skin involvement, respectively. The incidence of severe adverse reactions and infections was 8% and 2%, respectively. Additionally, several retrospective studies and systematic reviews have demonstrated that rituximab (RTX) can stabilize or improve pulmonary function in IIM-ILD patients [ 12 , 41 – 43 , 11 ]. These results suggest that RTX is a potential therapeutic option for IIM-ILD, particularly for patients with recurrent, refractory, or recent progressive disease. However, there is a need to be vigilant about the risk of infections.

CD19

CD19 is one of the specific surface markers of B cells, expressed from early pro-B cells to the plasmablasts cell stage. Overexpression in mice leads to autoantibody production and loss of tolerance, while deficiency reduces autoantibody production. CAR-T cell therapy, effective in malignant tumors, is emerging in autoimmune diseases. Recently, five refractory SLE patients were successfully treated with CD19-targeted CAR T cell monotherapy [ 44 ]. Compared to the monoclonal antibody CD20, CD19-targeted CAR-T cells offer rapid and sustained B cell depletion in peripheral blood, bone marrow, and lymphoid tissues. In recent case reports, the efficacy of CD19-targeted CAR T-cell therapy in the treatment of ASS has been notably effective. Specifically, two 41-year-old male patients with anti-Jo-1 + ASS exhibited significant clinical improvement and sustained disease stability following CD19-directed CAR T-cell therapy. Prior to treatment, these patients presented with profound myopathy and progressive respiratory distress, which were refractory to multiple immunosuppressive agents, including rituximab and intravenous immunoglobulins. Post-CAR T-cell therapy, rapid clinical amelioration was observed in both patients, with seroconversion to negative for anti-Jo-1 antibodies, a decrease in creatine kinase levels, improved manual muscle test scores, and enhanced physician global assessment scores [ 17 , 18 ]. Subsequently, an anther 44-year-old patient with anti-Jo-1 + ASS exhibited poor response to multiple therapeutic agents. Following treatment with CD19-directed CAR T-cell therapy as a salvage therapy, the patient experienced symptomatic improvement and remained medication-free during a 150-day follow-up period [ 19 ]. During subsequent follow-up, all three patients achieved clinical remission. Despite variability in therapeutic approaches and outcomes, long-term remission was maintained post-complete B cell reconstitution, potentially associated with a reset of the autoimmune response [ 45 ]. Researchers in China have effectively treated one patient with intractable immune-mediated necrotizing myopathy (IMNM) and two patients with systemic sclerosis [ 46 ] using allogeneic CD19-CAR-T cells. Patients with SRP-IMNM demonstrated substantial therapeutic benefits, achieving a TIS of 100, which was maintained through 6 months. Creatine kinase (CK) levels plummeted, nearing the normal range. There was a marked enhancement in global assessment scores, muscle strength as measured by MMT-8, health-related quality of life as indicated by HAQ-DI, and extramacular disease activity (EMDA). Anti-SRP antibodies vanished, and indicators of myositis activity showed significant amelioration; muscle MRI depicted diminished inflammation and improved atrophy [ 21 ]. This significant advancement has substantially reduced the cost of CAR-T cell therapy and shortened the preparation time, thereby expanding the application of CAR-T treatment in the field of rheumatology and immunology. In addition to CD19-targeted CAR-T therapy, a 25-year-old male with anti-SRP + IMNM, unresponsive to multiple immunosuppressants including rituximab and stem cell therapy, was treated with BCMA (B Cell Maturation Antigen)-targeted CAR T-cell therapy. Post-treatment, there was a sustained decrease in autoantibody levels, enhanced muscle strength, reduced creatine kinase levels, and diminished myositis signals on muscle MRI. There were also positive shifts in immune cell parameters [ 20 ]. Preliminary evidence supports the use of CAR-T cell therapy in IIM, hinting at possible long-term remission without ongoing medication. However, more clinical research is needed to confirm these results. CAR-T cell therapy is a promising area in rheumatology and immunology, with potential as a targeted treatment. While it shows great promise, current cases are limited, and further studies are required to establish the long-term efficacy and safety of CAR-T therapy in IIM. Beyond CD19 CAR-T therapy, CD19xCD3 Bispecific T cell engagers (BiTE) blinatumomab was used to treat six refractory RA patients unresponsive to multiple medications. All patients showed rapid reductions in RA disease activity, with improvements in synovitis on ultrasound and FAPI-PET-CT, and decreased autoantibody levels. The treatment was well-tolerated [ 47 ]. This study supports the use of BiTEs for refractory RA and their exploration in other B cell-mediated autoimmune diseases like IIM.

CD38

CD38 is a type II transmembrane glycoprotein found on B cells, T cells, and other immune cells, with both enzymatic activity and receptor functions. It regulates cell migration, signal transduction, and adhesion, and as an ectoenzyme, it influences cellular growth and immune suppression [ 48 – 52 ]. In addition, CD38 is abnormally expressed in a variety of tumor cells and is closely related to the occurrence and development of tumors [ 53 – 56 ]. CD38 is highly expressed on plasmablasts and plasma cells. Targeting CD38 with daratumumab, an anti-CD38 monoclonal antibody, reduces B cell proliferation, differentiation, and IgG production stimulated by T cells. Studied for hematological malignancies and solid tumors, daratumumab was approved in 2015 for relapsed/refractory multiple myeloma in adults. It inhibits NF-κB activation and gene transcription in B cells, particularly affecting switched memory B cells. This suggests daratumumab may treat B cell-mediated diseases beyond its current use in malignant tumors [ 57 ]. Emerging research indicates that CD38 monoclonal antibodies may be effective in treating refractory systemic lupus erythematosus (SLE) [ 58 ]. Single-cell sequencing studies in DM reveal higher frequencies of CD19 + CD38 + B cells and in increased plasma cell proliferation anti-MDA5-positive patients, indicating their potential role in disease pathogenesis [ 33 , 36 ]. Holzer et al. recently reported the successful use of daratumumab in a case of MDA5-positive DM with refractory rapidly progressive interstitial lung disease (RP-ILD). The patient had not responded to various treatments, including corticosteroids, cyclophosphamide, tofacitinib, CSA, MMF, rituximab, and anakinra, and continued to have high levels of MDA5 antibodies. Flow cytometry revealed a high frequency of CD38-positive plasma cells. After 4 weeks of daratumumab treatment (weekly daratumumab 1800 mg subcutaneously), the patient experienced a gradual alleviation of symptoms by the fifth month of hospitalization, with the support of oxygen therapy being reduced, a tapering of corticosteroids, and an improvement in rash, muscle strength, and pulmonary function [ 14 ]. Daratumumab emerged as a salvage therapy for MDA5 + DM with RP-ILD, with Ostendorf also achieving successful rescue in a similar case post-ECMO. Pulmonary symptoms resolved following daratumumab treatment [ 15 ]. In the SRP-positive IMNM case, daratumumab also serve as a salvage therapy [ 16 ]. Research indicates daratumumab could be a salvage therapy for these myopathies, possibly by targeting long-lived plasma cells producing persistent antibodies that render standard treatments ineffective. Currently, only three cases of daratumumab use in refractory myopathies have been reported, with the addition of this CD38 monoclonal antibody as a last resort showing life-saving benefits after other treatments failed. A common feature among these patients is the persistently high titer of antibodies, which typically indicates poor treatment response and adverse prognosis. However, using CD38 monoclonal antibodies led to reduced titers and effective treatment.

BAFF/APRIL Inhibitors

BAFF, or B lymphocyte stimulator (Blys), and APRIL are crucial proteins that regulate B cell development and function. They are predominantly produced by immune cells, including monocytes, macrophages, and dendritic cells, and function as cytokines to enhance B cell survival and maturation. High BAFF/APRIL levels are linked to autoantibody production in autoimmune diseases such as SLE, Sjögren’s syndrome, and rheumatoid arthritis [ 46 ]. Targeting the BAFF/APRIL system can significantly impact the entire process of B cell differentiation from the transitional stage to plasma cells. BAFF inhibition primarily reduces peripheral mature B cells and precursors of autoantibody production. APRIL inhibition directly depletes plasma cells, leading to a rapid decline in autoantibody levels. Belimumab, a monoclonal antibody against BAFF, is effective in SLE and is linked to increased BAFF levels in IIM, correlating with CK levels [ 59 ]. It reduces BAFF after corticosteroid treatment and may benefit refractory IIM patients [ 60 ]. Serum BAFF levels are significantly higher in MDA5 + DM patients compared to those with ASS and healthy controls, with the highest levels in patients who also have rapidly progressive interstitial lung disease (RP-ILD). BAFF is an independent risk factor for RP-ILD development [ 61 ]. In refractory anti-SRP IMNM patients, BAFF-R expression is upregulated in muscle tissue compared to non-refractory patients [ 62 ], and BAFF transcript levels are significantly increased in IIM patients, with B cells and plasma cells expressing BAFF-R in muscle tissue [ 35 , 63 , 64 ]. Then, the mRNA expression of BAFF, APRIL, and CXCL-13 was significantly higher in IBM and PM compared to controls [ 65 ]. Additionally, some case reports and retrospective studies suggest that BAFF inhibitors are effective [ 22 ]. Subsequently, a retrospective study on belimumab’s effectiveness in recurrent IIM, including 13 cases (6 DM, 7 JDM), showed that after 12 weeks of treatment, 12 patients met the primary outcome. Corticosteroid use decreased, MITAX scores dropped, and creatine kinase levels improved, with clinical stability sustained at 24 weeks. No severe adverse effects were reported [ 24 ]. Similarly, a recent study on Telitacicept for IIM (9 IMNM, 1 DM, 1 PM) found good improvement in most patients: 6 significantly, 4 moderately, and 1 mildly. There were improvements in activity, MMT-8 scores, extramuscular assessments, and CK levels, with some ILD patients gaining muscle strength [ 25 ]. Two studies have yielded similar and promising results. BAFF/APRIL inhibitors can reduce muscle enzymes, enhance muscle strength, and decrease the use of corticosteroids. However, in a recent RCT with 17 patients, belimumab did not meet its primary endpoint, but more patients in the belimumab group achieved a TIS ≥ 40 and DOI at weeks 40 and 64 compared to placebo (55.5% vs 33.3% and 33.3% vs 16.7%, respectively; both p = NS). Two belimumab patients met the primary efficacy outcome after week 40, while none in the placebo group did [ 23 ]. The study’s non-significant results might be due to its small sample size. Most B cell depleting therapies can hinder B cells from maturing into plasma cells but do not impact long-lived plasma cells, which seem to sustain autoimmune responses through their antibody production. However, BAFF/APRIL inhibitors also influence long-lived plasma cells. Current research on BAFF/APRIL inhibitors in the context of idiopathic inflammatory myopathies (IIM) suggests that, compared to RTX, BAFF/APRIL inhibitors may be a relatively safer treatment option, even in refractory DM, where it has shown efficacy. Future studies necessitate larger-scale, prospective trials to further validate the efficacy and safety of belimumab in IIM.

Other Emerging Cell Therapies

BCMA-Targeted T-Cell-Engager

Bispecific T cell engagers (BiTE) are small protein engineering constructs that can simultaneously bind to T cells and B cells, activating the patient’s own immune system to treat diseases [ 66 ]. BiTE molecules have shown definite therapeutic efficacy in some solid tumors and hematological malignancies [ 66 – 68 ]. This year, published studies have suggested that BiTE molecules are efficacious in the treatment of autoimmune diseases [ 26 , 47 ]. Notably, a case study featured in the New England Journal of Medicine (NEJM) detailed a 24-year-old individual with treatment-resistant MDA5-positive DM [ 26 ]. Following a 12-week course of therapy, there was a notable decline in MDA5 antibody levels, along with significant amelioration in Clinical Disease Activity Score in DM (CDASI), Manual Muscle Testing-8 (MMT-8), Health Assessment Questionnaire, and DM Life Quality Score indices. The sole adverse effect observed was a reduction in IgG levels. This therapeutic approach could emerge as a highly promising alternative to CAR-T cell therapy.

ANTI-FcRn

Intravenous immunoglobulin (IVIG) is one of the effective therapies for idiopathic inflammatory myopathies (IIM) [ 69 ], with one of its mechanisms of action being the competitive inhibition of neonatal Fc receptors (FcRn), which clears potentially pathogenic autoantibodies. Efgartigimod is a human IgG1 Fc fragment that blocks FcRn, decreasing IgG levels and treating AChR-positive myasthenia gravis in adults. It is also being studied for other autoimmune conditions, including chronic inflammatory demyelinating polyneuropathy, immune thrombocytopenia [ 70 ]. In preclinical trials prior to clinical studies, efgartigimod was demonstrated to reduce total IgG levels, including pathogenic HMGCR antibodies ( p < 0.001), in the serum and muscle of a humanized IMNM mouse model, thereby preventing further muscle necrosis and promoting muscle fiber regeneration [ 71 ]. A recent study of 7 patients with refractory IMNM, 5 with HMGCR and 2 with SRP antibodies, showed that 57% improved clinically within 4 weeks of treatment. TIS scores increased from 4 to 8 weeks. Only one mild headache was reported. The study hints at the effectiveness of Efgartigimod in reducing IgG levels for IMNM, suggesting it could be a promising treatment to shorten disease duration and reduce chronic symptoms [ 27 ]. Additionally, this drug is currently under investigation as a potential novel therapy in clinical trials.

Summary

Due to the complex and highly heterogeneous pathogenesis of idiopathic inflammatory myopathies (IIM), their treatment poses significant challenges. Researchers have now recognized the pivotal role of B cells in IIM, and the depletion of B cells holds great potential in the treatment of IIM. Targeted B cell therapy has demonstrated promising results in reducing disease manifestations and improving the prognosis of IIM patients. Furthermore, treatment modalities such as T cell engagers and CAR-T offer a novel approach to therapy. High-quality clinical studies are needed to confirm the efficacy, safety, and long-term outcomes of B cell depletion therapy in IIM patients. As research on B cell-targeted therapies continues to advance, the potential to improve the prognosis of IIM patients may continue to expand, offering hope for more effective and targeted treatments in the future.

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Tao Liu and Bo Chen contributed equally to this work.

Author Contribution

All authors were involved in the conceptualization and design of the study. Tao Liu, Bo Chen, Geng Yin and Qibing Xie were responsible for material preparation, data collection, and analysis. The initial draft of the manuscript was written by Tao Liu and Bo Chen, with all authors providing feedback on previous versions. All authors have read and approved the final manuscript.

Funding

This study was supported by Sichuan Science and Technology Program (2025ZNSFSC0638(G.Y.), 2024YFFK0062 (Q.B.X.).

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Consent for Publication

All participants provided written informed consent for the publication of this study and any accompanying images.

Competing Interests

The authors declare no competing interests.

References

1. Allenbach Y Benveniste O Goebel HH Stenzel W Integrated classification of inflammatory myopathies Neuropathol Appl Neurobiol 2017 43 1 62 81 10.1111/nan.12380 28075491 Allenbach Y, Benveniste O, Goebel HH, Stenzel W (2017) Integrated classification of inflammatory myopathies. Neuropathol Appl Neurobiol 43(1):62–81. 10.1111/nan.12380 28075491 10.1111/nan.12380

2. Mariampillai K Granger B Amelin D Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies JAMA Neurol 2018 75 12 1528 1537 10.1001/jamaneurol.2018.2598 30208379 PMC6583199 Mariampillai K, Granger B, Amelin D et al (2018) Development of a new classification system for idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific autoantibodies. JAMA Neurol 75(12):1528–1537. 10.1001/jamaneurol.2018.2598 30208379 10.1001/jamaneurol.2018.2598 PMC6583199

3. Ahn GY Suh CH Kim YG Park YB Shim SC Lee SH Lee SS Bae SC Yoo DH Efficacy and safety of rituximab in Korean patients with refractory inflammatory myopathies J Korean Med Sci 2020 35 38 e335 10.3346/jkms.2020.35.e335 32989931 PMC7521958 Ahn GY, Suh CH, Kim YG, Park YB, Shim SC, Lee SH, Lee SS, Bae SC, Yoo DH (2020) Efficacy and safety of rituximab in Korean patients with refractory inflammatory myopathies. J Korean Med Sci 35(38). 10.3346/jkms.2020.35.e335 32989931 10.3346/jkms.2020.35.e335 PMC7521958

4. Manwatkar A, Naresh K, Mathew J, Nair AV, Goel R, Yadav B, Prakash JAJ, Das JK, Sivadasan A (2024) Comparison of rituximab efficacy in treatment-naïve and refractory inflammatory myopathies: experiences from a tertiary care centre. Rheumatology (Oxford) 00:1–8. 10.1093/rheumatology/keae307 10.1093/rheumatology/keae307 38814804

5. Campochiaro C Farina N De Luca G Batani V Trignani G Vignale D Palmisano A Matucci-Cerinic M Dagna L Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies Arthritis Res Ther 2024 26 1 79 10.1186/s13075-024-03310-z 38570792 PMC10988925 Campochiaro C, Farina N, De Luca G, Batani V, Trignani G, Vignale D, Palmisano A, Matucci-Cerinic M, Dagna L (2024) Effectiveness and safety of mycophenolate mofetil and rituximab combination therapy for immune idiopathic myopathies. Arthritis Res Ther 26(1):79. 10.1186/s13075-024-03310-z 38570792 10.1186/s13075-024-03310-z PMC10988925

6. Marie I Dominique S Janvresse A Levesque H Menard JF Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome Respir Med 2012 106 4 581 587 10.1016/j.rmed.2012.01.001 22280877 Marie I, Dominique S, Janvresse A, Levesque H, Menard JF (2012) Rituximab therapy for refractory interstitial lung disease related to antisynthetase syndrome. Respir Med 106(4):581–587. 10.1016/j.rmed.2012.01.001 22280877 10.1016/j.rmed.2012.01.001

7. Doyle TJ Dhillon N Madan R Rituximab in the treatment of interstitial lung disease associated with antisynthetase syndrome: a multicenter retrospective case review J Rheumatol 2018 45 6 841 850 10.3899/jrheum.170541 29606668 PMC5984657 Doyle TJ, Dhillon N, Madan R et al (2018) Rituximab in the treatment of interstitial lung disease associated with antisynthetase syndrome: a multicenter retrospective case review. J Rheumatol 45(6):841–850. 10.3899/jrheum.170541 29606668 10.3899/jrheum.170541 PMC5984657

8. Andersson H Sem M Lund MB Aalokken TM Gunther A Walle-Hansen R Garen T Molberg O Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease Rheumatology (Oxford) 2015 54 8 1420 1428 10.1093/rheumatology/kev004 25740830 Andersson H, Sem M, Lund MB, Aalokken TM, Gunther A, Walle-Hansen R, Garen T, Molberg O (2015) Long-term experience with rituximab in anti-synthetase syndrome-related interstitial lung disease. Rheumatology (Oxford) 54(8):1420–1428. 10.1093/rheumatology/kev004 25740830 10.1093/rheumatology/kev004

9. So H Wong VTL Lao VWN Pang HT Yip RML Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis Clin Rheumatol 2018 37 7 1983 1989 10.1007/s10067-018-4122-2 29713969 So H, Wong VTL, Lao VWN, Pang HT, Yip RML (2018) Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis. Clin Rheumatol 37(7):1983–1989. 10.1007/s10067-018-4122-2 29713969 10.1007/s10067-018-4122-2

10. Mao MM Xia S Guo BP Qian WP Zheng ZX Peng XM Chen RC Luo Q Han Q Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD Respir Med 2020 172 105983 10.1016/j.rmed.2020.105983 33032789 Mao MM, Xia S, Guo BP, Qian WP, Zheng ZX, Peng XM, Chen RC, Luo Q, Han Q (2020) Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD. Respir Med 172. 10.1016/j.rmed.2020.105983 33032789 10.1016/j.rmed.2020.105983

11. Narvaez J Canadillas E Castellvi I Alegre JJ Vicens-Zygmunt V Bermudo G Vidal-Montal P Molina Molina M Nolla JM Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome Arthritis Res Ther 2024 26 1 122 10.1186/s13075-024-03353-2 38890654 PMC11184916 Narvaez J, Canadillas E, Castellvi I, Alegre JJ, Vicens-Zygmunt V, Bermudo G, Vidal-Montal P, Molina Molina M, Nolla JM (2024) Rituximab in the treatment of progressive interstitial lung disease associated with the antisynthetase syndrome. Arthritis Res Ther 26(1):122. 10.1186/s13075-024-03353-2 38890654 10.1186/s13075-024-03353-2 PMC11184916

12. Maher TM Tudor VA Saunders P Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial Lancet Respir Med 2023 11 1 45 54 10.1016/S2213-2600(22)00359-9 36375479 Maher TM, Tudor VA, Saunders P et al (2023) Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med 11(1):45–54. 10.1016/S2213-2600(22)00359-9 36375479 10.1016/S2213-2600(22)00359-9

13. Oddis CV Reed AM Aggarwal R Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial Arthritis Rheum 2013 65 2 314 324 10.1002/art.37754 23124935 PMC3558563 Oddis CV, Reed AM, Aggarwal R et al (2013) Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum 65(2):314–324. 10.1002/art.37754 23124935 10.1002/art.37754 PMC3558563

14. Holzer MT Nies JF Oqueka T Huber TB Kotter I Krusche M Successful rescue therapy with daratumumab in rapidly progressive interstitial lung disease caused by MDA5-positive dermatomyositis Chest 2023 163 1 e1 e5 10.1016/j.chest.2022.08.2209 36628678 Holzer MT, Nies JF, Oqueka T, Huber TB, Kotter I, Krusche M (2023) Successful rescue therapy with daratumumab in rapidly progressive interstitial lung disease caused by MDA5-positive dermatomyositis. Chest 163(1):e1–e5. 10.1016/j.chest.2022.08.2209 36628678 10.1016/j.chest.2022.08.2209

15. Ostendorf L Muench F Thormahlen L Galbavy Z Korner R Nee J Schneider U Rescue combination treatment of anti-MDA5-associated ARDS with daratumumab RMD Open 2023 9 3 e003238 10.1136/rmdopen-2023-003238 37479497 PMC10364176 Ostendorf L, Muench F, Thormahlen L, Galbavy Z, Korner R, Nee J, Schneider U (2023) Rescue combination treatment of anti-MDA5-associated ARDS with daratumumab. RMD Open 9(3). 10.1136/rmdopen-2023-003238 37479497 10.1136/rmdopen-2023-003238 PMC10364176

16. Landon-Cardinal O Allard-Chamard H Chapdelaine H Doucet S Rich E Bourre-Tessier J Daratumumab as a rescue therapy in severe refractory anti-SRP immune-mediated necrotising myopathy Ann Rheum Dis 2023 10.1136/ard-2022-223541 36609342 Landon-Cardinal O, Allard-Chamard H, Chapdelaine H, Doucet S, Rich E, Bourre-Tessier J (2023) Daratumumab as a rescue therapy in severe refractory anti-SRP immune-mediated necrotising myopathy. Ann Rheum Dis. 10.1136/ard-2022-223541 36609342 10.1136/ard-2022-223541

17. Pecher AC Hensen L Klein R CD19-Targeting CAR-T cells for myositis and interstitial lung disease associated with antisynthetase syndrome JAMA 2023 329 24 2154 2162 10.1001/jama.2023.8753 37367976 PMC10300719 Pecher AC, Hensen L, Klein R et al (2023) CD19-Targeting CAR-T cells for myositis and interstitial lung disease associated with antisynthetase syndrome. JAMA 329(24):2154–2162. 10.1001/jama.2023.8753 37367976 10.1001/jama.2023.8753 PMC10300719

18. Muller F Boeltz S Knitza J CD19-targeted CAR-T cells in refractory antisynthetase syndrome Lancet 2023 401 10379 815 818 10.1016/S0140-6736(23)00023-5 36930673 Muller F, Boeltz S, Knitza J et al (2023) CD19-targeted CAR-T cells in refractory antisynthetase syndrome. Lancet 401(10379):815–818. 10.1016/S0140-6736(23)00023-5 36930673 10.1016/S0140-6736(23)00023-5

19. Taubmann J Knitza J Muller F Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies Rheumatology (Oxford) 2024 63 1 e12 e14 10.1093/rheumatology/kead330 37432378 PMC10765150 Taubmann J, Knitza J, Muller F et al (2024) Rescue therapy of antisynthetase syndrome with CD19-targeted CAR-T cells after failure of several B-cell depleting antibodies. Rheumatology (Oxford) 63(1):e12–e14. 10.1093/rheumatology/kead330 37432378 10.1093/rheumatology/kead330 PMC10765150

20. Qin C Dong MH Zhou LQ Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy Proc Natl Acad Sci U S A 2024 121 6 e2315990121 10.1073/pnas.2315990121 38289960 PMC10861907 Qin C, Dong MH, Zhou LQ et al (2024) Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy. Proc Natl Acad Sci U S A 121(6). 10.1073/pnas.2315990121 38289960 10.1073/pnas.2315990121 PMC10861907

21. Wang X Wu X Tan B Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis Cell 2024 187 18 4890 4904 e4899 10.1016/j.cell.2024.06.027 39013470 Wang X, Wu X, Tan B et al (2024) Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis. Cell 187(18):4890-4904 e4899. 10.1016/j.cell.2024.06.027 39013470 10.1016/j.cell.2024.06.027

22. Cui BB Tian YR Ma XY Yin G Xie Q Belimumab for immune-mediated necrotizing myopathy associated with anti-SRP antibodies: a case report and retrospective review of patients treated with anti-B-cell therapy in a single center and literature Front Immunol 2021 12 777502 10.3389/fimmu.2021.777502 34925350 PMC8675000 Cui BB, Tian YR, Ma XY, Yin G, Xie Q (2021) Belimumab for immune-mediated necrotizing myopathy associated with anti-SRP antibodies: a case report and retrospective review of patients treated with anti-B-cell therapy in a single center and literature. Front Immunol 12. 10.3389/fimmu.2021.777502 34925350 10.3389/fimmu.2021.777502 PMC8675000

23. Marder G Quach T Chadha P Belimumab treatment of adult idiopathic inflammatory myopathy Rheumatology (Oxford) 2023 10.1093/rheumatology/kead281 PMC10907809 37326854 Marder G, Quach T, Chadha P et al (2023) Belimumab treatment of adult idiopathic inflammatory myopathy. Rheumatology (Oxford). 10.1093/rheumatology/kead281 10.1093/rheumatology/kead281 PMC10907809 37326854

24. Liu Y Li Y Shen T Zhang H Luo S Zhang Q Dang X Li X Long H Belimumab ameliorates symptoms and disease activity in dermatomyositis and juvenile dermatomyositis patients refractory to standard therapy: a retrospective observational study J Am Acad Dermatol 2024 10.1016/j.jaad.2024.04.060 38697217 Liu Y, Li Y, Shen T, Zhang H, Luo S, Zhang Q, Dang X, Li X, Long H (2024) Belimumab ameliorates symptoms and disease activity in dermatomyositis and juvenile dermatomyositis patients refractory to standard therapy: a retrospective observational study. J Am Acad Dermatol. 10.1016/j.jaad.2024.04.060 38697217 10.1016/j.jaad.2024.04.060

25. Gao H Lin J Yang M Gui M Ji S Bu B Li Y Telitacicept add-on therapy in refractory idiopathic inflammatory myopathy: insights from a pilot study Rheumatology (Oxford) 2024 10.1093/rheumatology/keae601 39495163 Gao H, Lin J, Yang M, Gui M, Ji S, Bu B, Li Y (2024) Telitacicept add-on therapy in refractory idiopathic inflammatory myopathy: insights from a pilot study. Rheumatology (Oxford). 10.1093/rheumatology/keae601 39495163 10.1093/rheumatology/keae601

26. Hagen M Bucci L Böltz S BCMA-targeted T-cell-engager therapy for autoimmune disease N Engl J Med 2024 391 9 867 869 10.1056/NEJMc2408786 39231353 Hagen M, Bucci L, Böltz S et al (2024) BCMA-targeted T-cell-engager therapy for autoimmune disease. N Engl J Med 391(9):867–869. 10.1056/NEJMc2408786 39231353 10.1056/NEJMc2408786

27. Yang M Yuan J Wang Y Hao H Zhang W Wang Z Yuan Y Zhao Y Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod Front Immunol 2024 15 1447182 10.3389/fimmu.2024.1447182 39502686 PMC11534618 Yang M, Yuan J, Wang Y, Hao H, Zhang W, Wang Z, Yuan Y, Zhao Y (2024) Treatment of refractory immune-mediated necrotizing myopathy with efgartigimod. Front Immunol 15. 10.3389/fimmu.2024.1447182 39502686 10.3389/fimmu.2024.1447182 PMC11534618

28. Greenberg SA Bradshaw EM Pinkus JL Pinkus GS Burleson T Due B Bregoli L O'Connor KC Amato AA Plasma cells in muscle in inclusion body myositis and polymyositis Neurology 2005 65 11 1782 1787 10.1212/01.wnl.0000187124.92826.20 16344523 Greenberg SA, Bradshaw EM, Pinkus JL, Pinkus GS, Burleson T, Due B, Bregoli L, O’Connor KC, Amato AA (2005) Plasma cells in muscle in inclusion body myositis and polymyositis. Neurology 65(11):1782–1787. 10.1212/01.wnl.0000187124.92826.20 16344523 10.1212/01.wnl.0000187124.92826.20

29. Pinal-Fernandez I Muñoz-Braceras S Casal-Dominguez M Pathological autoantibody internalisation in myositis Ann Rheum Dis 2024 83 11 1549 1560 10.1136/ard-2024-225773 38902010 PMC11493519 Pinal-Fernandez I, Muñoz-Braceras S, Casal-Dominguez M et al (2024) Pathological autoantibody internalisation in myositis. Ann Rheum Dis 83(11):1549–1560. 10.1136/ard-2024-225773 38902010 10.1136/ard-2024-225773 PMC11493519

30. Arouche-Delaperche L Allenbach Y Amelin D Pathogenic role of anti-signal recognition protein and anti-3-hydroxy-3-methylglutaryl-CoA reductase antibodies in necrotizing myopathies: myofiber atrophy and impairment of muscle regeneration in necrotizing autoimmune myopathies Ann Neurol 2017 81 4 538 548 10.1002/ana.24902 28224701 Arouche-Delaperche L, Allenbach Y, Amelin D et al (2017) Pathogenic role of anti-signal recognition protein and anti-3-hydroxy-3-methylglutaryl-CoA reductase antibodies in necrotizing myopathies: myofiber atrophy and impairment of muscle regeneration in necrotizing autoimmune myopathies. Ann Neurol 81(4):538–548. 10.1002/ana.24902 28224701 10.1002/ana.24902

31. Anang DC Walter HAW Lim J B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies Rheumatology (Oxford) 2023 62 7 2585 2593 10.1093/rheumatology/keac602 36321862 PMC10321087 Anang DC, Walter HAW, Lim J et al (2023) B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies. Rheumatology (Oxford) 62(7):2585–2593. 10.1093/rheumatology/keac602 36321862 10.1093/rheumatology/keac602 PMC10321087

32. He J Liu Z Cao Y Single-cell landscape of peripheral immune response in patients with anti-melanoma differentiation-associated gene 5 dermatomyositis Rheumatology (Oxford) 2023 10.1093/rheumatology/kead597 37941459 He J, Liu Z, Cao Y et al (2023) Single-cell landscape of peripheral immune response in patients with anti-melanoma differentiation-associated gene 5 dermatomyositis. Rheumatology (Oxford). 10.1093/rheumatology/kead597 37941459 10.1093/rheumatology/kead597

33. Ye Y Chen Z Jiang S Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications Nat Commun 2022 13 1 6458 10.1038/s41467-022-34145-4 36309526 PMC9617246 Ye Y, Chen Z, Jiang S et al (2022) Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications. Nat Commun 13(1):6458. 10.1038/s41467-022-34145-4 36309526 10.1038/s41467-022-34145-4 PMC9617246

34. Bergua C Chiavelli H Allenbach Y In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy Ann Rheum Dis 2019 78 1 131 139 10.1136/annrheumdis-2018-213518 30309969 Bergua C, Chiavelli H, Allenbach Y et al (2019) In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. Ann Rheum Dis 78(1):131–139. 10.1136/annrheumdis-2018-213518 30309969 10.1136/annrheumdis-2018-213518

35. Preusse C Paesler B Nelke C Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis Acta Neuropathol 2022 144 2 353 372 10.1007/s00401-022-02438-z 35612662 PMC9288384 Preusse C, Paesler B, Nelke C et al (2022) Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis. Acta Neuropathol 144(2):353–372. 10.1007/s00401-022-02438-z 35612662 10.1007/s00401-022-02438-z PMC9288384

36. Sugimori Y Iwasaki Y Takeshima Y Transcriptome profiling of immune cell types in peripheral blood reveals common and specific pathways involved in the pathogenesis of myositis-specific antibody-positive inflammatory myopathies ACR Open Rheumatol 2023 5 2 93 102 10.1002/acr2.11521 36651871 PMC9926062 Sugimori Y, Iwasaki Y, Takeshima Y et al (2023) Transcriptome profiling of immune cell types in peripheral blood reveals common and specific pathways involved in the pathogenesis of myositis-specific antibody-positive inflammatory myopathies. ACR Open Rheumatol 5(2):93–102. 10.1002/acr2.11521 36651871 10.1002/acr2.11521 PMC9926062

37. Haq SA Tournadre A Idiopathic inflammatory myopathies: from immunopathogenesis to new therapeutic targets Int J Rheum Dis 2015 18 8 818 825 10.1111/1756-185X.12736 26385431 Haq SA, Tournadre A (2015) Idiopathic inflammatory myopathies: from immunopathogenesis to new therapeutic targets. Int J Rheum Dis 18(8):818–825. 10.1111/1756-185X.12736 26385431 10.1111/1756-185X.12736

38. Fasano S Gordon P Hajji R Loyo E Isenberg DA Rituximab in the treatment of inflammatory myopathies: a review Rheumatology (Oxford) 2017 56 1 26 36 10.1093/rheumatology/kew146 27121778 Fasano S, Gordon P, Hajji R, Loyo E, Isenberg DA (2017) Rituximab in the treatment of inflammatory myopathies: a review. Rheumatology (Oxford) 56(1):26–36. 10.1093/rheumatology/kew146 27121778 10.1093/rheumatology/kew146

39. Johnson SR, Bernstein EJ, Bolster MB, Chung JH, Danoff SK, George MD, Khanna D, Guyatt G, Mirza RD, Aggarwal R, Allen A Jr, Assassi S, Buckley L, Chami HA, Corwin DS, Dellaripa PF, Domsic RT, Doyle TJ, Falardeau CM, Frech TM, Gibbons FK, Hinchcliff M, Johnson C, Kanne JP, Kim JS, Lim SY, Matson S, McMahan ZH, Merck SJ, Nesbitt K, Scholand MB, Shapiro L, Sharkey CD, Summer R, Varga J, Warrier A, Agarwal SK, Antin-Ozerkis D, Bemiss B, Chowdhary V, Dematte D'Amico JE, Hallowell R, Hinze AM, Injean PA, Jiwrajka N, Joerns EK, Lee JS, Makol A, McDermott GC, Natalini JG, Oldham JM, Saygin D, Lakin KS, Singh N, Solomon JJ, Sparks JA, Turgunbaev M, Vaseer S, Turner A, Uhl S, Ivlev I (2024) 2023 American college of rheumatology (ACR)/american college of chest physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases. Arthritis Rheumatol. 76(8):1182-1200. 10.1002/art.42861 10.1002/art.42861 PMC12646471 38978310

40. Zhen C Hou Y Zhao B Ma X Dai T Yan C Efficacy and safety of rituximab treatment in patients with idiopathic inflammatory myopathies: a systematic review and meta-analysis Front Immunol 2022 13 1051609 10.3389/fimmu.2022.1051609 36578492 PMC9791086 Zhen C, Hou Y, Zhao B, Ma X, Dai T, Yan C (2022) Efficacy and safety of rituximab treatment in patients with idiopathic inflammatory myopathies: a systematic review and meta-analysis. Front Immunol 13. 10.3389/fimmu.2022.1051609 36578492 10.3389/fimmu.2022.1051609 PMC9791086

41. Jang Y Yoon HY Kim HS The efficacy and safety of rituximab in patients with idiopathic inflammatory myopathy-associated interstitial lung disease: case series J Clin Med 2023 12 10 3406 10.3390/jcm12103406 37240516 PMC10219281 Jang Y, Yoon HY, Kim HS (2023) The efficacy and safety of rituximab in patients with idiopathic inflammatory myopathy-associated interstitial lung disease: case series. J Clin Med 12(10). 10.3390/jcm12103406 37240516 10.3390/jcm12103406 PMC10219281

42. Zhao Y Gao Y Petnak T Cheungpasitporn W Thongprayoon C Zhang X Moua T Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis Respir Res 2022 23 1 164 10.1186/s12931-022-02082-x 35729565 PMC9215101 Zhao Y, Gao Y, Petnak T, Cheungpasitporn W, Thongprayoon C, Zhang X, Moua T (2022) Effect size of rituximab on pulmonary function in the treatment of connective-tissue disease-related interstitial lung disease: a systematic review and meta-analysis. Respir Res 23(1):164. 10.1186/s12931-022-02082-x 35729565 10.1186/s12931-022-02082-x PMC9215101

43. Ge Y Li S Tian X He L Lu X Wang G Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis responds to rituximab therapy Clin Rheumatol 2021 40 6 2311 2317 10.1007/s10067-020-05530-5 33411136 Ge Y, Li S, Tian X, He L, Lu X, Wang G (2021) Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis responds to rituximab therapy. Clin Rheumatol 40(6):2311–2317. 10.1007/s10067-020-05530-5 33411136 10.1007/s10067-020-05530-5

44. Mackensen A Muller F Mougiakakos D Anti-CD19 CAR-T cell therapy for refractory systemic lupus erythematosus Nat Med 2022 28 10 2124 2132 10.1038/s41591-022-02017-5 36109639 Mackensen A, Muller F, Mougiakakos D et al (2022) Anti-CD19 CAR-T cell therapy for refractory systemic lupus erythematosus. Nat Med 28(10):2124–2132. 10.1038/s41591-022-02017-5 36109639 10.1038/s41591-022-02017-5

45. Muller F Taubmann J Bucci L CD19 CAR-T cell therapy in autoimmune disease - a case series with follow-up N Engl J Med 2024 390 8 687 700 10.1056/NEJMoa2308917 38381673 Muller F, Taubmann J, Bucci L et al (2024) CD19 CAR-T cell therapy in autoimmune disease - a case series with follow-up. N Engl J Med 390(8):687–700. 10.1056/NEJMoa2308917 38381673 10.1056/NEJMoa2308917

46. Gordts S Uzieblo K Neumann C Van den Bussche E Rossi G Validity of the self-report psychopathy scales (SRP-III full and short versions) in a community sample Assessment 2017 24 3 308 325 10.1177/1073191115606205 26384737 Gordts S, Uzieblo K, Neumann C, Van den Bussche E, Rossi G (2017) Validity of the self-report psychopathy scales (SRP-III full and short versions) in a community sample. Assessment 24(3):308–325. 10.1177/1073191115606205 26384737 10.1177/1073191115606205

47. Bucci L Hagen M Rothe T Bispecific T cell engager therapy for refractory rheumatoid arthritis Nat Med 2024 30 6 1593 1601 10.1038/s41591-024-02964-1 38671240 Bucci L, Hagen M, Rothe T et al (2024) Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat Med 30(6):1593–1601. 10.1038/s41591-024-02964-1 38671240 10.1038/s41591-024-02964-1

48. Hartman WR Pelleymounter LL Moon I CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system Leuk Lymphoma 2010 51 7 1315 1325 10.3109/10428194.2010.483299 20470215 PMC2892000 Hartman WR, Pelleymounter LL, Moon I et al (2010) CD38 expression, function, and gene resequencing in a human lymphoblastoid cell line-based model system. Leuk Lymphoma 51(7):1315–1325. 10.3109/10428194.2010.483299 20470215 10.3109/10428194.2010.483299 PMC2892000

49. Zeng F Zhang J Jin X Liao Q Chen Z Luo G Zhou Y Effect of CD38 on B-cell function and its role in the diagnosis and treatment of B-cell-related diseases J Cell Physiol 2022 237 7 2796 2807 10.1002/jcp.30760 35486480 Zeng F, Zhang J, Jin X, Liao Q, Chen Z, Luo G, Zhou Y (2022) Effect of CD38 on B-cell function and its role in the diagnosis and treatment of B-cell-related diseases. J Cell Physiol 237(7):2796–2807. 10.1002/jcp.30760 35486480 10.1002/jcp.30760

50. Li W Liang L Liao Q Li Y Zhou Y CD38: An important regulator of T cell function Biomed Pharmacother 2022 153 113395 10.1016/j.biopha.2022.113395 35834988 Li W, Liang L, Liao Q, Li Y, Zhou Y (2022) CD38: An important regulator of T cell function. Biomed Pharmacother 153. 10.1016/j.biopha.2022.113395 35834988 10.1016/j.biopha.2022.113395

51. Li W Li Y Jin X Liao Q Chen Z Peng H Zhou Y CD38: A significant regulator of macrophage function Front Oncol 2022 12 775649 10.3389/fonc.2022.775649 35251964 PMC8891633 Li W, Li Y, Jin X, Liao Q, Chen Z, Peng H, Zhou Y (2022) CD38: A significant regulator of macrophage function. Front Oncol 12. 10.3389/fonc.2022.775649 35251964 10.3389/fonc.2022.775649 PMC8891633

52. Trepiakas R Pedersen AE Met O Svane IM Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function Vaccine 2009 27 16 2213 2219 10.1016/j.vaccine.2009.02.015 19428835 Trepiakas R, Pedersen AE, Met O, Svane IM (2009) Addition of interferon-alpha to a standard maturation cocktail induces CD38 up-regulation and increases dendritic cell function. Vaccine 27(16):2213–2219. 10.1016/j.vaccine.2009.02.015 19428835 10.1016/j.vaccine.2009.02.015

53. Gao L Du X Li J Qin FX Evolving roles of CD38 metabolism in solid tumour microenvironment Br J Cancer 2023 128 4 492 504 10.1038/s41416-022-02052-6 36396822 PMC9938187 Gao L, Du X, Li J, Qin FX (2023) Evolving roles of CD38 metabolism in solid tumour microenvironment. Br J Cancer 128(4):492–504. 10.1038/s41416-022-02052-6 36396822 10.1038/s41416-022-02052-6 PMC9938187

54. Heimes AS, Riedel N, Almstedt K et al (2023) Prognostic impact of CD38- and IgkappaC-positive tumor-infiltrating plasma cells in triple-negative breast cancer. Int J Mol Sci 24(20). 10.3390/ijms242015219 10.3390/ijms242015219 PMC10607675 37894900

55. Zhang Y Wu J Zhang H Wu C The Regulation between CD4(+)CXCR5(+) Follicular Helper T (Tfh) Cells and CD19(+)CD24(hi)CD38(hi) regulatory B (Breg) cells in gastric cancer J Immunol Res 2022 2022 9003902 10.1155/2022/9003902 36339942 PMC9629923 Zhang Y, Wu J, Zhang H, Wu C (2022) The Regulation between CD4(+)CXCR5(+) Follicular Helper T (Tfh) Cells and CD19(+)CD24(hi)CD38(hi) regulatory B (Breg) cells in gastric cancer. J Immunol Res 2022. 10.1155/2022/9003902 36339942 10.1155/2022/9003902 PMC9629923

56. Kanayama M Luo J CD38-Induced apoptosis and mitochondrial damage is restored by nicotinamide in prostate cancer Front Mol Biosci 2022 9 890402 10.3389/fmolb.2022.890402 35677882 PMC9168365 Kanayama M, Luo J (2022) CD38-Induced apoptosis and mitochondrial damage is restored by nicotinamide in prostate cancer. Front Mol Biosci 9. 10.3389/fmolb.2022.890402 35677882 10.3389/fmolb.2022.890402 PMC9168365

57. Verhoeven D, Grinwis L, Marsman C, Jansen MH, Consortium TB, Van Leeuwen EM, Kuijpers TW (2023) B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responses. Life Sci Alliance 6(9). 10.26508/lsa.202302214 10.26508/lsa.202302214 PMC10331639 37419630

58. Ostendorf L Burns M Durek P Targeting CD38 with daratumumab in refractory systemic lupus erythematosus N Engl J Med 2020 383 12 1149 1155 10.1056/NEJMoa2023325 32937047 Ostendorf L, Burns M, Durek P et al (2020) Targeting CD38 with daratumumab in refractory systemic lupus erythematosus. N Engl J Med 383(12):1149–1155. 10.1056/NEJMoa2023325 32937047 10.1056/NEJMoa2023325

59. Krystufkova O Vallerskog T Helmers SB Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies Ann Rheum Dis 2009 68 6 836 843 10.1136/ard.2008.091405 18628284 Krystufkova O, Vallerskog T, Helmers SB et al (2009) Increased serum levels of B cell activating factor (BAFF) in subsets of patients with idiopathic inflammatory myopathies. Ann Rheum Dis 68(6):836–843. 10.1136/ard.2008.091405 18628284 10.1136/ard.2008.091405

60. Krystufkova O Hulejova H Mann HF Pecha O Putova I Ekholm L Lundberg IE Vencovsky J Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis Arthritis Res Ther 2018 20 1 158 10.1186/s13075-018-1650-8 30053824 PMC6062864 Krystufkova O, Hulejova H, Mann HF, Pecha O, Putova I, Ekholm L, Lundberg IE, Vencovsky J (2018) Serum levels of B-cell activating factor of the TNF family (BAFF) correlate with anti-Jo-1 autoantibodies levels and disease activity in patients with anti-Jo-1positive polymyositis and dermatomyositis. Arthritis Res Ther 20(1):158. 10.1186/s13075-018-1650-8 30053824 10.1186/s13075-018-1650-8 PMC6062864

61. Shi Y You H Liu C Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis Orphanet J Rare Dis 2024 19 1 170 10.1186/s13023-024-03153-6 38637830 PMC11027411 Shi Y, You H, Liu C et al (2024) Elevated serum B-cell activator factor levels predict rapid progressive interstitial lung disease in anti-melanoma differentiation associated protein 5 antibody positive dermatomyositis. Orphanet J Rare Dis 19(1):170. 10.1186/s13023-024-03153-6 38637830 10.1186/s13023-024-03153-6 PMC11027411

62. Zhao Y Zhang W Liu Y Wang Z Yuan Y Factors associated with refractory autoimmune necrotizing myopathy with anti-signal recognition particle antibodies Orphanet J Rare Dis 2020 15 1 181 10.1186/s13023-020-01431-7 32641139 PMC7341563 Zhao Y, Zhang W, Liu Y, Wang Z, Yuan Y (2020) Factors associated with refractory autoimmune necrotizing myopathy with anti-signal recognition particle antibodies. Orphanet J Rare Dis 15(1):181. 10.1186/s13023-020-01431-7 32641139 10.1186/s13023-020-01431-7 PMC7341563

63. Kryštůfková O Barbasso Helmers S Venalis P Malmström V Lindroos E Vencovský J Lundberg IE Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies Arthritis Res Ther 2014 16 5 454 10.1186/s13075-014-0454-8 25301447 PMC4234835 Kryštůfková O, Barbasso Helmers S, Venalis P, Malmström V, Lindroos E, Vencovský J, Lundberg IE (2014) Expression of BAFF receptors in muscle tissue of myositis patients with anti-Jo-1 or anti-Ro52/anti-Ro60 autoantibodies. Arthritis Res Ther 16(5):454. 10.1186/s13075-014-0454-8 25301447 10.1186/s13075-014-0454-8 PMC4234835

64. Baek A Park HJ Na SJ Shim DS Moon JS Yang Y Choi YC The expression of BAFF in the muscles of patients with dermatomyositis J Neuroimmunol 2012 249 1–2 96 100 10.1016/j.jneuroim.2012.04.006 22575417 Baek A, Park HJ, Na SJ, Shim DS, Moon JS, Yang Y, Choi YC (2012) The expression of BAFF in the muscles of patients with dermatomyositis. J Neuroimmunol 249(1–2):96–100. 10.1016/j.jneuroim.2012.04.006 22575417 10.1016/j.jneuroim.2012.04.006

65. Carstens PO Mullar LM Wrede A Zechel S Wachowski MM Brandis A Krause S Zierz S Schmidt J Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis Front Immunol 2023 14 1177721 10.3389/fimmu.2023.1177721 37731487 PMC10508232 Carstens PO, Mullar LM, Wrede A, Zechel S, Wachowski MM, Brandis A, Krause S, Zierz S, Schmidt J (2023) Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis. Front Immunol 14. 10.3389/fimmu.2023.1177721 37731487 10.3389/fimmu.2023.1177721 PMC10508232

66. Einsele H Borghaei H Orlowski RZ Subklewe M Roboz GJ Zugmaier G Kufer P Iskander K Kantarjian HM The BiTE (bispecific T-cell engager) platform: development and future potential of a targeted immuno-oncology therapy across tumor types Cancer 2020 126 14 3192 3201 10.1002/cncr.32909 32401342 Einsele H, Borghaei H, Orlowski RZ, Subklewe M, Roboz GJ, Zugmaier G, Kufer P, Iskander K, Kantarjian HM (2020) The BiTE (bispecific T-cell engager) platform: development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer 126(14):3192–3201. 10.1002/cncr.32909 32401342 10.1002/cncr.32909

67. Moreau P Garfall AL van de Donk N Teclistamab in relapsed or refractory multiple myeloma N Engl J Med 2022 387 6 495 505 10.1056/NEJMoa2203478 35661166 PMC10587778 Moreau P, Garfall AL, van de Donk N et al (2022) Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med 387(6):495–505. 10.1056/NEJMoa2203478 35661166 10.1056/NEJMoa2203478 PMC10587778

68. Yu B Jiang T Liu D BCMA-targeted immunotherapy for multiple myeloma J Hematol Oncol 2020 13 1 125 10.1186/s13045-020-00962-7 32943087 PMC7499842 Yu B, Jiang T, Liu D (2020) BCMA-targeted immunotherapy for multiple myeloma. J Hematol Oncol 13(1):125. 10.1186/s13045-020-00962-7 32943087 10.1186/s13045-020-00962-7 PMC7499842

69. Aggarwal R Charles-Schoeman C Schessl J Trial of intravenous immune globulin in dermatomyositis N Engl J Med 2022 387 14 1264 1278 10.1056/NEJMoa2117912 36198179 Aggarwal R, Charles-Schoeman C, Schessl J et al (2022) Trial of intravenous immune globulin in dermatomyositis. N Engl J Med 387(14):1264–1278. 10.1056/NEJMoa2117912 36198179 10.1056/NEJMoa2117912

70. Heo YA Efgartigimod: first approval Drugs 2022 82 3 341 348 10.1007/s40265-022-01678-3 35179720 PMC8855644 Heo YA (2022) Efgartigimod: first approval. Drugs 82(3):341–348. 10.1007/s40265-022-01678-3 35179720 10.1007/s40265-022-01678-3 PMC8855644

71. Julien S van der Woning B De Ceuninck L Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy Rheumatology (Oxford) 2023 10.1093/rheumatology/kead298 37335864 Julien S, van der Woning B, De Ceuninck L et al (2023) Efgartigimod restores muscle function in a humanized mouse model of immune-mediated necrotizing myopathy. Rheumatology (Oxford). 10.1093/rheumatology/kead298 37335864 10.1093/rheumatology/kead298