Chimeric antigen receptor-T (CAR-T) cells are genetically engineered T cells that has demonstrated significant success in treating hematologic tumors. The therapeutic landscape of CAR-T cell therapy is undergoing paradigm-shifting expansion into autoimmune disease management. Emerging clinical evidence demonstrates that engineered CAR-T cells can achieve unprecedented disease remission in the treatment of autoimmune diseases by efficiently depleting autoreactive B cells, thereby resetting the immune system, while maintaining favorable safety profiles. These encouraging results have motivated in-depth exploration into expanding the application of CAR-T cells to a broader spectrum of autoimmune diseases, as well as the development of advanced cell products with better efficacy and safety. This review systematically explores fundamental research and clinical applications of CAR-T cell therapy in autoimmune diseases, critically examines existing limitations, and proposes potential future directions. Significantly, the study elucidates structural characteristics of disease-associated autoantigens in autoimmune diseases, offering novel perspectives and technical frameworks for developing next-generation chimeric autoantibody receptor-T (CAAR-T) therapeutics with enhanced precision.

New therapeutic options have recently emerged for patients with highly active, acetylcholine receptor antibody-positive (AChR-Ab) generalized myasthenia gravis (gMG), including fast-acting, endplate-protective agents such as complement C5 inhibitors (C5-I) and neonatal Fc receptor inhibitors (FcRn-I). However, objective biomarkers beyond clinical scoring systems are lacking to guide individualized treatment decisions.

Prior studies identified subsets of patients with Takayasu arteritis (TAK) based on angiographic patterns of disease in cohorts from India and North America. This study aimed to validate these patterns in a TAK cohort from Turkey and determine the role of genetics in arterial patterns.

Human membrane-bound CD137 (mCD137) is a well-known costimulatory molecule; however, it is alternatively spliced into two transcripts (sCD137-1, 2) whose function is not yet known. Here, we show that sCD137 isoforms lack the CRD4 region and form unique structures compared to mCD137. Human activated Tregs produce both CD137 splice isoforms, which are rapidly upregulated after cell activation, and identify an activated Treg phenotype along with FOXP3, CTLA4, and sCTLA4. We engineered recombinant Fc-Hu-sCD137 variants, which are immunosuppressive, inhibiting IFN-γ secretion and proliferation in purified CD4 and CD8 T cells in an APC-independent manner. These effects are mediated by the downregulation of S6 and 4EBP1 of the mTOR complex 1 pathway. Human sCD137 variants, in contrast to the membrane-bound form, are immunosuppressive and may be a novel treatment for inflammation and autoimmunity.

Type 1 autoimmune pancreatitis (AIP) is a rare, immune-mediated pancreatic disease prone to relapse. The influence of age on relapse risk remains unclear. This study aimed to determine whether age at diagnosis is associated with disease relapse.

Elderly-onset systemic sclerosis (SSc) is relatively uncommon, and its clinical phenotype and prognostic implications remain poorly characterized, with conflicting evidence regarding disease course and outcomes.

Patients with immunological diseases exhibit distinct comorbidity patterns, categorized into low comorbidity, polyautoimmunity, and polyinflammation profiles. This retrospective cohort study aimed to validate these profiles in rheumatoid arthritis (RA) patients, examine their longitudinal trajectories, and assess their impact on treatment persistence.

Immune-mediated inflammatory diseases (IMIDs, distinct from IMiDs, immunomodulatory drugs) pose major therapeutic challenges due to complex pathophysiology, limited treatment durability, and associated adverse effects. T cell engagers (TCEs) and antibody-drug conjugates (ADCs) offer innovative approaches that leverage antibody specificity to precisely target pathogenic immune cells. TCEs redirect T cell cytotoxicity to eliminate autoreactive B cells and plasma cells, showing efficacy in diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. In contrast, ADCs deliver immunomodulatory payloads to disease-relevant cells, with agents like ABBV-154 and brentuximab vedotin showing promise in rheumatoid arthritis and systemic sclerosis. However, challenges such as cytokine release syndrome with TCEs and off- and on-target toxicities with ADCs highlight the need for optimal target selection and innovative design. This review provides a comprehensive comparison of the mechanisms, current evidence, and future directions of TCEs and ADCs in IMIDs, highlighting their potential to address unmet needs in disease management.

The concept of severity in psoriatic arthritis (PsA) remains inconsistently defined, often conflated with disease activity. This scoping review aimed to explore how severity has been defined in the PsA literature and to identify criteria used to characterize severe disease.

Levamisole, once used as anthelminthic or immunomodulator, is now a common cocaine adulterant. It is linked to a systemic vasculopathy/vasculitis. Our purpose was to review its clinical, serological, and histopathological features.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, and its course is often accompanied by multiple organ damage. The mortality rate of SLE exhibits a "bimodal pattern", namely the early death peak is primarily attributed to infection and lupus activity, while the late death peak lists cardiovascular diseases (CVD) caused by atherosclerosis (AS) as the leading cause of death. Mitochondria, as the hub of energy metabolism and the multi-dimensional regulatory center of cellular functions, play a key role in the occurrence and development of AS plaques under the pathological background of SLE. This review systematically sorted out the mitochondrial dysfunction mechanisms of different immune cells and endothelial cells in SLE, and deeply expounded their influence pathways on the pathological process of AS. Furthermore, this article explores the current clinical treatment strategies for SLE and analyzes the therapeutic potential of mitochondrial-targeted intervention measures.

To test the efficacy and safety of methotrexate plus low-dose prednisone in patients with idiopathic retroperitoneal fibrosis.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with an unclear etiology, in which abnormal copper homeostasis has been shown in the blood and synovial fluid of the joints of patients. As an essential trace element in the human body, copper plays a critical role in various biological processes, including antioxidant defense, angiogenesis, and bone maintenance. However, the accumulation of excessive copper ions has been shown to be positively correlated with disease activity and the degree of inflammation in RA. While copper-bound ceruloplasmin may exert anti-inflammatory effects, excess "free" copper acts as a potent pro-oxidant, driving oxidative stress, cartilage and bone destruction, inflammatory responses, as well as pannus formation. The recently discovered copper-dependent cell death pathway, named cuproptosis, further adds to the complexity of its role in RA. This review integrates current research advances on the double-edged role of copper in the pathogenesis of RA, systematically examines copper-related therapeutic strategies, and finally analyzes their potential applications and challenges. The aim is to harness the physiological functions of copper while mitigating its pathological effects, thereby opening new avenues for the diagnosis and precision treatment of RA.

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative treatment in autoimmune diseases. Relmacabtagene autoleucel (relma-cel) is an autologous, CD19-directed CAR-T cell product developed with a commercial-ready process in China. This study evaluates the safety and efficacy of relma-cel in patients with moderately to severely active systemic lupus erythematosus (SLE).

Despite treatment advances, some rheumatoid arthritis (RA) patients fail to achieve remission with biological/targeted synthetic DMARDs. We prospectively evaluated 200 patients to determine if interferon profiles and autoantibodies predict treatment outcomes. A significant positive correlation between rheumatoid factor and IFN-γ levels was observed. Patients with high IFN-γ/low IFN-α2 profiles achieved significantly higher remission rates and demonstrated elevated B cell-stimulating cytokines with distinct immunological clustering patterns. This group showed superior responses to IL-6 inhibitors. Anti-carbamylated protein IgM antibodies differed significantly between groups. Interferon profiling offers a practical screening approach for personalized therapy selection in RA.

Thyroid peroxidase antibody (TPOAb) positivity is the most important risk factor for hypothyroidism and determines thyroid function follow-up during pregnancy. TPOAb positivity is usually defined by manufacturer cut-offs which typically derived from non-pregnant populations. However, as a state of immune tolerance, pregnancy can affect TPOAb concentrations. To improve the understanding of clinical relevance of TPOAb concentrations during pregnancy, we investigated the association of TPOAbs with maternal thyroid function.

Mycophenolate mofetil (MMF) and rituximab (RTX) are recommended as first-line therapies for skin and interstitial lung disease (ILD) involvement in systemic sclerosis (SSc). However, data on their combined use remain limited. This study evaluated the efficacy and safety of MMF/RTX combination therapy compared to each drug alone.

Rheumatoid arthritis (RA) causes disability, chronic pain, and reduced quality of life. Preclinical studies suggest glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may reduce inflammation and protect joint tissues. This study compared GLP-1 RAs with non-GLP-1 RAs on the risk of RA in patients with type 2 diabetes mellitus (T2DM).

Interleukin-23 (IL-23) plays a pivotal role in the intricate interplay between the skin, gut, and joints, contributing significantly to the pathogenesis of various inflammatory diseases including psoriasis, psoriatic arthritis (PsA), inflammatory bowel disease (IBD) and Behcet's disease. In recent years, several IL-23 inhibitors have been granted approval for the treatment of psoriasis, PsA and IBD. As up to one-third of patients diagnosed with psoriasis may go on to develop PsA and given the strong immunogenetic pathway incrimination of the IL-23 pathway in both psoriasis and PsA, dermatological lead therapy for psoriasis may therefore delay the development of PsA. Furthermore, patients with psoriasis or PsA are associated with increased risk of developing IBD. There is also evidence for psoriasis-directed therapy preventing IBD in keeping with the known pivotal role of IL-23 in both intestinal homeostasis and in the pathogenesis of IBD, including ulcerative colitis and Crohn's disease. This review discusses the multifaceted roles of IL-23 in regulating immune response and maintaining tissue homeostasis within the skin-gut-joint axis. In particular, the use of IL-23 inhibitors in trials in patients with psoriasis, IBD and PsA patients will also be discussed in relation to reverse translational immunology insights around inflammation in these domains.

Central nervous system (CNS) infections contribute to the development of neuroinflammation and neurodegenerative diseases. However, the mechanisms underlying the correlation between CNS infection and subsequent inflammatory course remain largely unknown.

Human autoantibodies have a long history of being valuable reagents to identify and characterize unique subcellular compartments, macromolecular complexes, and their individual components. One such discovery started as a unique cell-cycle related immunofluorescence pattern characterized as autoantibody targets localized in S and G2 phase nuclei of tissue culture cells, which became known as the "SG2NA" (SG2 nuclear antigen). These descriptions were followed by the identification of a calmodulin-binding protein family named 'striatin' that was later identified as three paralogs: Striatin/STRN1, Striatin-3/STRN3/SG2NA, and Striatin-4/STRN4/Zinedin. Many subsequent reports have used the designations SG2NA and striatin interchangeably. This report reviews the history of SG2NA and clarifies that striatin-3 is indeed a target autoantigen of some autoimmune sera, but commercially available striatin-3 antibodies or human sera that react with striatin-3 do not produce a SG2 phase nuclear staining pattern on HEp-2 cells. Hence, future reports should not use anti-SG2NA and anti-striatin interchangeably.