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Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy.

Despite the advancements in targeted biologic therapy for immune-mediated inflammatory diseases (IMIDs), significant challenges persist, including challenges in drug maintenance, primary and secondary non-responses, and adverse effects. Recent data have strengthened the evidence supporting stem cell therapy as an experimental salvage therapy into a standard treatment option. Recent preclinical and clinical studies suggested that chimeric antigen receptor T cell (CAR-T) therapy, which depleting tissue and bone marrow B cells, may lead to improvement, even inducing long-lasting remissions for pa

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the d

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… Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus Ann. Rheum. Dis. 2019 78 1363 1370 10.1136/annrheumdis-2019-215434 31300459 PMC6788882 75. Chang H.H. Dwivedi N. Nicholas A.P. Ho I.C. … The W620 Polymorphism in PTPN22 Disrupts Its Interaction With Peptidylarginine Deiminase Type 4 and Enhances Citrullination and NETosis Arthritis Rheumatol. 2015 67 2323 2334 10.1002/art.39215 26019128 76. Li D. Matta B. Song S. Nelson V. Diggins K. Simpfendorfer K.R. Gregersen P.K. Linsley P. …

Histone modifications: Unveiling the epigenetic enigma of degenerative skeletal diseases.

Degenerative skeletal diseases, including osteoporosis, osteoarthritis, and intervertebral disc degeneration, are prevalent age-related conditions characterized by progressive tissue degeneration and functional decline. Histone modifications are covalent modifications of histone residues, catalyzed by specific enzymes, that modulate chromatin architecture and transcriptional activity. Accumulating evidence highlights the critical involvement of histone modifications in orchestrating disease-associated transcriptional programs. In osteoporosis, histone modifications regulate osteoblast and oste

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… Moreover, other modifications with limited investigation but experimental validation have also been reported, including citrullination, SUMOylation, ADP-ribosylation, and biotinylation [ 32 ] ( Fig. 1 ). … | ARTDs (ARTD1-17); ARTCs (ARTC1-5); ADPRT1a; ADPRT2; Sirtuins | PARG; TARG1; ARH1; ARH3; MacroD1; MacroD2 | PBM; Macrodomain; WWE domain; PBZ domain | [ [104] , [105] , [106] ] O-GlcNAcylation | 1984 | OGT | OGA | NA | [ [107] , [108] , [109] ] Biotinylation | 2001 | HCS | NA | NA | [ 110 , 111 ] Citrullination …

Secondary Osteoporosis and Metabolic Bone Diseases.

Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by control

Прогнозирование аутоиммунных заболеваний на основе глубокого обучения.

Аутоиммунные заболевания представляют собой сложную группу заболеваний, вызванных иммунной системой, ошибочно наносящей удар по тканям тела. Их этиология включает в себя множество факторов, таких, как генетика, экологические факторы и аномалии в иммунных клетках, что затрудняет прогнозирование и лечение. Т клетки как один из ключевых компонентов иммунной системы играют важнейшую роль в иммунной системе человека и оказывают значительное воздействие на патогенез аутоиммунных заболеваний. Ряд исследований показали, что рецепторы Т-клеток (ТКР) могут быть вовлечены в патогенез различных аутоиммунн

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in

Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune disease. It causes persistent joint inflammation, aberrant tissue growth, and progressive joint deterioration. T cells have a key role in the onset of RA. They identify and trigger other immune cells, and produce inflammatory signals such as interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Prolonged inflammation and tissue damage are caused by an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells. Additionally, the condition is exacerbated by uncontrolled cytokine netwo

Окисляющие молекулярные сигнатуры в неизлечимых заболеваниях: систематический обзор комплексных подходов к машинному обучению и системной биологии.

Окисляющий стресс является одним из основных факторов патогенеза иммунных заболеваний в результате его воздействия на клеточный метаболизм, митохондриальную функцию, иммунную сигнализацию и воспалительную травму тканей. Разрушение гомеостазиса способствует метаболическому перепрограммированию и постоянной активации врожденной и адаптивной иммунной реакции, что способствует прогрессированию заболеваний через многочисленные подстрекательские и аутоиммунные расстройства. Последние достижения в области высокопроизводительных молекулярных технологий привели к созданию крупномасштабных многомерных н

Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducin

Oral Communication abstracts

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Risk assessment and prevention of cancer-associated venous thromboembolism in ambulatory patients with solid malignancies.

Venous thromboembolism remains a major cause of morbidity and mortality among ambulatory cancer patients, necessitating effective risk assessment and prevention strategies. Despite the availability of risk assessment models and guidelines recommending primary thromboprophylaxis with low-molecular-weight heparins or direct oral anticoagulants, the application of these strategies is inconsistent. This review provides an overview of the current state-of-the-art venous thromboembolism risk assessment and thromboprophylaxis in ambulatory patients with cancer, focusing on existing risk assessment mo

The changes in global burden of autoimmune diseases two years after the COVID-19 pandemic: a trend analysis based on the Global Burden of Disease Study 2021.

BACKGROUND: Data on the epidemiological changes in the global burden of autoimmune diseases (ADs) after the Coronavirus disease 2019 (COVID-19) pandemic is lacking. This study investigated the impact of the COVID-19 pandemic on the global burden of ADs, including psoriasis (PsO), inflammatory bowel disease (IBD), type 1 diabetes (T1DM), rheumatoid arthritis (RA), and multiple sclerosis (MS). METHODS: Age-standardized rates (ASR), including incidence (ASIR), prevalence (ASPR), disability-adjusted life years (DALYs), and death (ASDR), were extracted from the Global Burden of Disease Study 2021

Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy.

The hepatitis B virus (HBV) infection leads to chronic hepatitis, cirrhosis, and hepatocarcinoma. However, about 20% of patients experience extrahepatic manifestations such as polyarteritis nodosa, non-rheumatoid arthritis, non-Hodgkin lymphoma, cryoglobulinemic vasculitis, and glomerulonephritis. These influence the patient's morbidity, quality of life and mortality. The treatment of an HBV infection is based on nucleotide analogues (NAs) which are safe and effective for the suppression of HBV-DNA in almost 100% of cases. A few studies have shown that NAs induce a viral response and an improv

Multiplatform plasma fingerprinting in cancer cachexia: a pilot observational and translational study.

BACKGROUND: Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge o

Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies.

Autoimmunity refers to an organism's immune response against its own healthy cells, tissues, or components, potentially leading to irreversible damage to vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T and B cells. The disruption of immunological tolerance, characterized by the failure of these mechanisms, results in the aberrant activation of autoreactive lymphocytes that target self-tissues, culminating in the pathogenesis of autoimmune disorders. Genetic predispositions, environmental exposures, and immun

Antibody-drug conjugates in clinical trials for lymphoid malignancies and multiple myeloma.

Antibody-drug conjugates (ADC) represent a distinct family of chemoimmunotherapy agents. ADCs are composed of monoclonal antibodies conjugated to cytotoxic payloads via specialized chemical linkers. ADCs therefore combine the immune therapy with targeted chemotherapy. Due to the distinct biomarkers associated with lymphocytes and plasma cells, ADCs have emerged as a promising treatment option for lymphoid malignancies and multiple myeloma. Several ADCs have been approved for clinical applications: brentuximab vedotin, inotuzumab ozogamicin, moxetumomab pasudotox, and polatuzumab vedotin. More

The next frontier in antibody-drug conjugates: challenges and opportunities in cancer and autoimmune therapy.

Antibody-Drug Conjugates (ADCs) have achieved significant success in cancer therapy by combining the targeting specificity of monoclonal antibodies with cytotoxic payloads. However, the concomitant issue of drug resistance has become increasingly prominent, with primary mechanisms including alterations in target antigen expression, impaired drug transport, and inhibition of cell death pathways. ADCs have also shown emerging therapeutic potential in the treatment of autoimmune diseases; for instance, ABBV-3373 has achieved initial success in this area, yet it also faces unique challenges such a

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

CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.

Although current treatments for autoimmune diseases can effectively control symptoms, they rarely lead to cures and often require lifelong use, accompanied by considerable adverse effects. This emphasizes the urgent need for more targeted therapies that offer long-term efficacy and curative potential. Chimeric antigen receptor (CAR) T-cell therapy presents a promising option by specifically targeting and eliminating autoreactive B cells, with the potential to reset the patient's immune system and promote long-term immune balance. Originally developed for treating hematologic malignancies, wher

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