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Sjögren Disease-B Cells at the Brink: From Autoimmunity to Lymphomagenesis and the Rise of Novel B Cell-Targeted Therapies.

Sjögren disease (SjD) is a common systemic autoimmune disorder characterized by inflammation of the exocrine glands, resulting in dryness. Patients frequently exhibit extraglandular manifestations affecting various organ systems. To date, there are no US Food and Drug Administration (FDA)-approved disease-modifying therapies for SjD. In this review, we explore the expanding field of SjD endotyping as a tool to enhance patient stratification, prognostication, and clinical decision-making. SjD endotypes driven by heightened B cell activity are linked to increased lymphoma risk. B cells play a ce

Targeted Small Molecules for Systemic Lupus Erythematosus: Drugs in the Pipeline.

Despite the uncertainty of the pathogenesis of systemic lupus erythematosus, novel small molecules targeting specific intracellular mechanisms of immune cells are being developed to reverse the pathophysiological processes. These targeted molecules have the advantages of convenient administration, lower production costs, and the lack of immunogenicity. The Janus kinases, Bruton's tyrosine kinases, and spleen tyrosine kinases are important enzymes for activating downstream signals from various receptors on immune cells that include cytokines, growth factor, hormones, Fc, CD40, and B-cell recept

Cutaneous secondary localization of multiple myeloma at Heparin injection sites.

We report two cases of multiple myeloma skin localizations at Heparin injections sites in patients followed at the University Hospital of Martinique. These skin manifestations on traumatized areas are a marker of aggressiveness in the natural history of multiple myeloma.

Chimeric antigen receptor T cell therapy: a new emerging landscape in autoimmune rheumatic diseases.

Chimeric antigen receptor T cell (CAR-T) therapy, an innovative immune cell therapy, has revolutionized the treatment landscape of haematological malignancies. The past 2 years has witnessed the successful application of CD19-targeting CAR constructs in refractory cases of autoimmune rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis and anti-synthetase syndrome. In comparison with existing B cell depletion therapies, targeting CD19 has demonstrated a more rapid and profound therapeutic effect, enabling drug-free remission with manageable adverse events. These promi

Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

Rare Synchronous Gastrointestinal Plasmacytomas of Colon and Stomach.

Gastrointestinal (GI) plasmacytomas, though relatively uncommon, can occur with or without multiple myeloma. The small intestine is the most commonly involved GI site, followed by stomach, colon, and esophagus. Synchronous plasmacytomas involving 2 anatomically distinct regions of gastrointestinal tract have never been reported in the literature. We report a case of a multiple myeloma patient who had acute-onset hematochezia and was found to have synchronous plasmacytomas of the colon and stomach.

Гетерогенность регулируемых клеток В в аутоиммунных заболеваниях: последствия для иммунного равновесия и терапевтических стратегий.

Регулирующие клетки В (Bregs) играют ключевую роль в поддержании иммунной терпимости и профилактике аутоиммунных заболеваний. Однако в условиях аутоиммунной среды количество и функции брега часто ухудшаются, что ведет к провоспалительной микроокружающей среде и регулированию иммунной дизакции. В рамках этого обзора проводится углубленный анализ последствий различных аутоиммунных заболеваний, включая множественный склероз, ревматоидный артрит, системный волчанье эритематосус, болезнь Шёгрена, аутоиммунный диабет и другие аутоиммунные заболевания. Резюмируя изменения в фенотипе Брегса и его функ

Chimeric Antigen Receptor T-Cells in Myasthenia Gravis: Advances, Safety Challenges, and Future Directions.

This review examines the emerging application of chimeric antigen receptor (CAR) T-cell therapy in myasthenia gravis (MG), with emphasis on safety, efficacy signals, and future therapeutic potential in treatment-refractory disease. A comprehensive literature search was conducted across PubMed, medRxiv, bioRxiv, and Google Scholar for studies published between January 1, 2010 and July 1, 2025, using the terms "CAR T-cell," "chimeric antigen receptor," and "myasthenia gravis." Eligible reports included clinical trials, case reports, case series, and mechanistic studies describing CAR T-cell ther

Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated substantial efficacy against various hematological malignancies. The remarkable success of CAR-T cell therapy in targeting B-cell malignancies has generated significant interest in its potential application for treating autoimmune diseases (ADs). By engineering T cells to express CARs that specifically recognize B-cell antigens, researchers aim to selectively eliminate or modulate the dysregulated autoimmune responses underlying disease pathology. Early clinical trials targeting the B-cell marker CD19 have shown promising results,

Developing role of B cells in the pathogenesis and treatment of chronic GVHD.

Chronic graft-versus-host disease (cGVHD) is a major complication affecting the long-term survival of patients after allogeneic haematopoietic stem cell transplantation. The mechanism of cGVHD is unclear, and while previous studies have primarily focused on T cells, the role of B cells in the pathogenesis of cGVHD has been less reported. However, current studies on cGVHD are increasingly focused on the important role of B cells. In this review, we will introduce the newest studies and examine the role of B cells in cGVHD in detail with respect to the following aspects: altered B cell subpopula

CAR T-Cells in Multiple Myeloma: State of the Art and Future Directions.

Despite recent therapeutic advances, the prognosis of multiple myeloma (MM) patients remains poor. Thus, new strategies to improve outcomes are imperative. Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape of B-cell malignancies, providing a potentially curative option for patients who are refractory to standard treatment. Long-term remissions achieved in patients with acute lymphoblastic leukemia and Non-Hodgkin Lymphoma encouraged its further development in MM. B-cell maturation antigen (BCMA)-targeted CAR T-cells have established outstanding results in heavi

Myelomatous ascites and pleural effusion in relapsed multiple myeloma.

Extramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

A randomized, placebo-controlled trial of the BTK inhibitor zanubrutinib in hospitalized patients with COVID-19 respiratory distress: immune biomarker and clinical findings.

BackgroundCytokine release triggered by a hyperactive immune response is thought to contribute to severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2)-related respiratory failure. Bruton tyrosine kinase (BTK) is involved in innate immunity, and BTK inhibitors block cytokine release. We assessed the next-generation BTK inhibitor zanubrutinib in SARS-CoV-2-infected patients with respiratory distress.MethodCohort 1 had a prospective, randomized, double-blind, placebo-controlled design; cohort 2 had a single-arm design. Adults with SARS-CoV-2 requiring hospitalization (without mechanica

Survival and Functional Outcomes in Patients with Thoracic Spinal Epidural Lymphoma with Spinal Cord Compromise: Three Cases Requiring Emergent Surgical Management.

Spinal epidural lymphoma is a rare pathological entity that usually responds well to chemotherapy. However, it occasionally requires immediate surgical treatment for progressive neurological symptoms caused by a bulky epidural mass and bone destruction. In the management of spinal epidural lymphoma, the role of surgical interventions has not yet been fully defined, and few reports on long-term functional outcomes are available. We report 3 cases of thoracic spinal epidural lymphoma that required emergent surgical management for neural decompression and were followed postoperatively over 2 year

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… Aggressive plasmablastic lymphoma of the thoracic spine presenting as acute spinal cord compression in a case of asymptomatic undiagnosed human immunodeficiency virus infection. Spine J. 2014;14(7):e1-5. doi: 10.1016/j.spinee.2013.12.018 13) Weller M, Martus P, Roth P, et al. …

Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β.

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Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy.

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use. B cell maturation antigen (BCMA), a transme

Targeted Therapy for Idiopathic Inflammatory Myopathy.

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune disorders characterized by chronic muscle inflammation and significant extramuscular involvement. A substantial proportion of patients exhibit refractory or relapsing disease despite conventional immunosuppressive therapies, necessitating the development of novel targeted treatments. Recent immunological advances have identified novel therapeutic targets-including B cells, T cells, cytokines and intracellular signalling pathways-paving the way for personalized treatment. Targeted therapies represent pr

Multiple myeloma presenting as a cervical intraforaminal tumor: A case report and review of literature.

Multiple myeloma (MM) is a hematological malignancy with characteristic clonal plasma cell proliferation and production of monoclonal immunoglobulins. Although it can often metastasize to the bony spine, completely extravertebral and extra-/intradural manifestations are exceedingly rare. In this case report, we describe a 51-year-old male patient with cervical extradural and intraforaminal MM who was surgically treated in our department. Clinical findings and radiological images were retrieved from medical records and an imaging system. This unusual localization of MM and similar cases in the

Staying Abreast of New Biomarkers in Hematology/Oncology.

There has been an increasing number of approvals for targeted therapies in oncology in the past decade, changing the treatment paradigm for many solid tumors and hematologic malignancies. At JADPRO Live 2023, presenters provided an in-depth review of cancer biomarkers, including testing methodology, recommended therapies, and how advanced practitioners can integrate results into clinical decision-making.

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA