Search Results (1,872)

Background/Objectives: Anti-mGluR1 encephalitis is a rare form of autoimmune encephalitis predominantly manifesting as acute/subacute cerebellar ataxia. We describe a newly diagnosed case series from our center and conduct a comprehensive review of reported cases worldwide to compare clinical manifestations, treatment options, and outcomes. Methods: We consecutively identified 11 patients at Peking Union Medical College Hospital, and additionally extracted clinical data from 42 previously published cases identified via PubMed and Google Scholar (search updated to 1 August 2025). Demographics, phenotypes, laboratory findings, imaging, treatment, and outcomes were systematically summarized. This pooled review was not prospectively registered, and extracted data from 21 published articles were analyzed alongside our 11 newly diagnosed cases. Results: The integrated cohort comprised 53 patients with anti-mGluR1 encephalitis, including 29 males and 24 females, with patients reported from Asia (n = 18), North America (n = 11), and Europe (n = 24). The median age at onset was 50 years (IQR 29.5–58.5; range 3–81), with North American patients presenting later than their Asian and European counterparts (median 60 vs. 48 and 45 years, respectively; all p < 0.05). Disease onset was subacute in most cases (58.7%). Comorbid tumors were present in nine patients, most commonly lymphomas. Clinical phenotypes were classified as pure cerebellar syndrome (n = 31), cerebellar ataxia with encephalitic features (n = 20), and non-cerebellar presentations (n = 2). Baseline severity differed across phenotypes (χ² = 35.7, p < 0.001). Regional variability in severity was observed but did not reach significance. CSF analyses revealed pleocytosis in 59% (23/39), elevated protein in 31.3% (5/16), and oligoclonal bands in 52.2% (12/23). MRI abnormalities were detected in 34.7% (17/49) of patients, with 21.9% (7/32) developing cerebellar atrophy on follow-up. Therapeutic strategies varied significantly across regions (p = 0.041), with Asian cohorts more frequently receiving long-term immunosuppression, European cohorts favoring combined regimens, and North American cases relying predominantly on first-line therapies. Overall, 65.9% (29/44) of patients clinically improved, 13.6% (6/44) relapsed and 20.5% (9/44) remained unaffected. Conclusions: Anti-mGluR1 encephalitis presents with significant clinical heterogeneity, ranging from cerebellar-dominant ataxia to neuropsychiatric or non-cerebellar phenotypes, and demonstrates differences in reported age of onset, disease severity, and therapeutic approaches across publication regions. Our findings underscore the importance of early recognition, sustained immunotherapy, and international collaboration to establish standardized, evidence-based management for this rare but disabling disorder. Full article

Autoimmune type 1 diabetes (T1D) results from the failure of the physiologic regulatory mechanisms that are designed to maintain immune tolerance to pancreatic beta cells. Consequently, the design of strategies to restore tolerance to beta cell antigens is an attractive objective of translational research. We have designed ultrasmall nanoparticles (NPs) loaded with a proinsulin (PI) fusion protein and an agonist for the aryl hydrocarbon receptor (AhR), a transcription factor promoting tolerance induction by different immune cells. We report that a 4 week-treatment with these NPs in non-obese diabetic (NOD) mice starting at disease onset induces temporary and sometimes durable disease remission. Mechanistically, short-term NP treatment induces a rapid depletion of islet infiltrates with a dramatic reduction in the number of CD8⁺ T cells and dendritic cells. This is accompanied by the emergence of B lymphocytes producing IL-10. In the rare mice that undergo durable disease remission, the disappearance of islet infiltrates is associated with the emergence of Foxp3⁺ CD4⁺ regulatory T cells, IFN-γ-producing memory T cells in the spleen, and draining lymph nodes (LNs). We conclude that treatment with these NPs could be of interest in the treatment of recent-onset autoimmune diabetes, but is unlikely to be sufficient for the induction of long-term remission as a stand-alone therapy. Full article

Background and Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system with rising prevalence in the Middle East. Real-world comparative data on disease-modifying therapies from this region remain limited. This retrospective study compared the clinical outcomes and tolerability of fingolimod and interferon beta-1a (IFN-β1a) among patients with relapsing–remitting multiple sclerosis treated at a large public referral hospital in Jordan. Materials and Methods: All eligible RRMS patients received fingolimod or IFN-β1a at a single tertiary hospital. The annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) scores, and adverse effect frequencies were analyzed using descriptive and inferential statistics. A full-cohort inclusion approach was applied instead of sample-size calculation, as all available cases at Al-Basheer Hospital (Amman, Jordan) were included. Results: Fingolimod-treated patients showed a significantly higher ARR than those on IFN-β1a (0.51 vs. 0.26, p = 0.016), an association likely influenced by treatment sequencing and baseline disease activity. EDSS distributions were similar between treatment groups, with most patients demonstrating mild disability (EDSS ≤ 3.5). IFN-β1a was linked to injection site reactions, while fingolimod was better tolerated. Conclusions: The higher observed relapse rate among fingolimod-treated patients possibly reflects treatment sequencing and underlying disease severity rather than pharmacologic efficacy, as fingolimod was commonly prescribed as an escalation therapy. These findings highlight the importance of individualized treatment selection and underscore the need for prospective studies incorporating standardized baseline disease activity measures to better inform multiple sclerosis care in Jordan and the wider Middle Eastern region. Full article

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiple and heterogeneous clinical manifestations (e.g., skin lesions, kidney damage, neuropsychiatric dysfunction), that primarily affects women and whose etiology remains unclear. Various therapies that regulate and reduce the immune system activity are in use or are being developed; however, many of them have serious side effects. Therefore, new approaches are needed to maximize remission periods and reduce associated side effects. In this review, we summarize the currently recommended therapeutic strategies. Furthermore, we hypothesize that the combined use of drugs targeting various dysregulated cellular processes in SLE (i.e., cytokine production, neutrophil extracellular traps (NETs), phagocytosis) might have therapeutic potential, at least in some disease phenotypes. Preliminary data show that Toll-like receptors 7/8 (TLR 7/8) inhibition (e.g., Enpatoran) may reduce interferon-α (IFN-α) production by monocytes and NET formation by neutrophils. Our hypothesis is that future therapies combining compounds that modulate the three cellular processes might result in a better disease management as current therapies. Full article

Background/Objectives: Interstitial pneumonia with autoimmune features (IPAF) is a recently defined entity characterized by interstitial lung disease (ILD) with clinical, serological, and radiological features suggestive of autoimmunity that do not fulfil the criteria for a defined connective tissue disease (CTD). This study aimed to evaluate the clinical characteristics, treatment modalities, and outcomes of patients with IPAF in a tertiary referral center. Methods: We retrospectively analyzed 72 patients who fulfilled the IPAF classification criteria. Demographic, clinical, serological, radiological, pulmonary function, treatment, and survival data were collected and evaluated. Logistic regression analysis was performed to identify factors associated with mortality. Results: The cohort consisted of 62.5% female patients, with a mean age of 62.7 (SD, 10.4) years at diagnosis. The most frequent radiological pattern was nonspecific interstitial pneumonia (83.3%). Raynaud’s phenomenon (6.9%) and arthritis (2.8%) were the most common rheumatological manifestations. Antinuclear antibodies positivity at titers ≥1:320 was observed in 27.8% of patients. Azathioprine was the most frequently prescribed agent (20.8%), followed by mycophenolate mofetil (11.1%). After a median follow-up of 30.1 months (IQR, 52.8), 16 patients (22.22%) died, with a 5-year survival rate of 70%. Glucocorticoid therapy at doses ≥20 mg/day was independently associated with increased mortality (OR 6.13 (95% CI 1.17–32.21). Conclusions: IPAF predominantly affects middle-aged females. Glucocorticoid use at doses ≥20 mg/day was associated with mortality; however, this observational association may reflect underlying disease severity rather than a causal effect of high-dose treatment. Further prospective studies are needed to optimize management strategies in patients with IPAF. Full article

Immune checkpoint inhibitors (ICIs) for cancer therapy may induce immune-related adverse events including myocarditis, which occurs infrequently but carries a high mortality rate. Crocins are the active constituents derived from Crocus sativus L. (saffron), and have demonstrated various bioactivities including anti-tumor, anti-inflammation, antioxidation, anti-ischemia, anti-aging, and neuroprotective effects. This study established a subcutaneous xenotransplanted tumor model of human liver cancer in nude mice to better mimic ICI-related myocarditis. Animal experimental results revealed that crocins improved cardiac function, relieved myocardial damage and autoimmune response, and suppressed oxidative stress and inflammatory reaction. Quantitative proteomics and Western blotting verification confirmed that crocins ameliorated experimental ICI-related myocarditis by targeting the Hpx/Nrf2/HO-1 pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I–HO-1, crocin II–Hpx, and crocin III–Nrf2. These findings shed new light on the development of therapeutic strategies for treating ICI-related myocarditis and provided the fundamental basis for expanding the clinical application of crocins. Full article

Chimeric antigen receptor (CAR)-T cell therapy has emerged as a transformative form of immunotherapy, enabling the precise engineering of T cells to recognize and eliminate pathogenic cells. In hematologic malignancies, CAR-T cells targeting CD19 or B cell maturation antigens have achieved remarkable remission rates and durable responses in patients with otherwise refractory disease. Despite these successes, extending CAR-T cell therapy to solid tumors remains challenging due to antigen heterogeneity, poor T cell infiltration, and the immunosuppressive tumor microenvironment (TME). Beyond oncology, CAR-T cell therapy has also shown promise in autoimmune diseases, where early clinical studies suggest that B cell-directed CAR-T cells can induce sustained remission in conditions such as systemic lupus erythematosus. This review highlights advances in CAR-T cell engineering, including DNA- and mRNA-based platforms for ex vivo and in vivo programming, and discusses emerging strategies to enhance CAR-T cell trafficking, persistence, and resistance to TME. Full article

Pulmonary embolism (PE) is one of the most serious complications of antiphospholipid syndrome (APS), a systemic autoimmune disorder defined by thrombotic events and persistent antiphospholipid antibodies (aPLA). PE occurs in 11–20% of patients and may constitute the initial clinical manifestation. Young and middle-aged women are most frequently affected, and triple-positive aPLA profiles markedly increase the risk of recurrence and long-term morbidity, including chronic thromboembolic pulmonary hypertension (CTEPH). This review article summarizes current evidence on the epidemiology, pathophysiology, diagnostic approach, and management of PE in APS. Key mechanisms include anti-β2-glycoprotein I-mediated endothelial and platelet activation, complement engagement, and neutrophil extracellular trap formation, resulting in immunothrombosis. Diagnostic pathways follow standard PE algorithms; however, chronically elevated D-dimer levels and lupus anticoagulant-related aPTT prolongation require careful interpretation and consideration. Long-term vitamin K antagonist therapy remains the standard of care, whereas direct oral anticoagulants are not recommended in high-risk APS. Future directions include improved risk stratification through detailed aPLA profiling and the use of emerging biomarkers, early screening for CTEPH, and the development of targeted therapies such as complement inhibition and anti-NETosis strategies. Full article

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system marked by inflammatory demyelination and progressive neurodegeneration. Although current immunomodulatory therapies can reduce relapse rates, they are often associated with limited long-term efficacy and adverse effects, highlighting the need for safer and more comprehensive complementary approaches. Dietary bioactive phytochemicals—notably, the polyphenols epigallocatechin-3-gallate (EGCG), curcumin, and resveratrol—have demonstrated potential to modulate the immune and inflammatory pathways implicated in MS pathogenesis. In addition to their immunomodulatory roles, emerging evidence suggests that these compounds also exert neuroprotective effects independent of immune modulation, including antioxidant activity, mitochondrial stabilization, and enhancement of neurotrophic signaling. Furthermore, recent studies identify the gut microbiota as a central mediator of MS pathophysiology and of how dietary phytochemicals are metabolized and exert their effects. This review examines experimental data evaluating the therapeutic potential of selected bioactive phytochemicals in MS, focusing on their mechanisms of action—including both immune-dependent and immune-independent neuroprotective effects—and interactions with the gut microbiota. Current limitations in translating findings from animal models to clinical settings are also discussed, and future directions for research in this evolving area are highlighted. Full article

Juvenile dermatomyositis (JDM) is a rare, idiopathic autoimmune disorder characterized by inflammation of both muscle and skin, with a significant contribution from the interferon (IFN) pathway in its pathogenesis. Here, we present the case of a 4-year-old boy with JDM who tested positive for Mi2-α and MDA5 antibodies and showed combined muscle and skin involvement. In view of his markedly elevated IFN signature, the Janus kinase (JAK) inhibitor baricitinib was introduced very early as a targeted steroid-sparing agent in addition to standard immunosuppressive therapy. The patient experienced marked clinical improvement, with resolution of skin lesions, normalization of MDA5 antibodies, and a pronounced reduction in the IFN signature. This case highlights the potential efficacy of JAK inhibition in managing JDM with a high IFN signature and supports a mechanism-based, interferon-targeted treatment approach, in line with emerging evidence in refractory JDM. Further studies are warranted to define the role of JAK inhibitors in the treatment of JDM. Full article

Background and Clinical Significance: Disorders caused by platelet-activating antibodies targeting platelet factor 4 (PF4) are recognized as the cause of severe thrombotic events and are not restricted to heparin-induced thrombocytopenia (HIT). Case Presentation: We report a 67-year-old man with thrombocytopenia and extensive portal-splenic-mesenteric vein thrombosis complicated by intestinal ischemia. Despite intravenous unfractionated heparin (UFH), his condition worsened toward pulmonary embolism, septic shock, and multi-organ failure. Thrombolysis with alteplase was also ineffective. Both thrombophilia testing and autoimmune panels were negative, including those for antiphospholipid syndrome. An anti-PF4 immune thrombotic disorder was hypothesized. Therefore, argatroban was initiated instead of UFH therapy and intravenous immune globulin (IVIG) was administered. The platelet count increased and the patient’s clinical condition progressively improved. An anti-PF4/heparin assay on a blood sample collected before IVIG was highly positive. Platelet activation assays did not demonstrate an increased activation after the addition of heparin (the Heparin-Induced Platelet Activation [HIPA] assay was negative) though increased activation was observed with the addition of PF4 (the PF4-Induced Platelet Activation [PIPA] assay was positive), thus defining a VITT-like syndrome. Conclusions: This case report highlights the crucial function of having adequate laboratory facilities available to disentangle different anti-PF4 disorders for an accurate definition of a specific diagnosis, such as VITT-like syndrome, thereby allowing for the most appropriate therapeutic management of these complex pathological conditions. The clinical suspicion of an anti-PF4 immune disorder should be considered in cases of severe, otherwise unexplained, thrombotic events associated with thrombocytopenia. Specific tests like HIPA and PIPA are essential for definitive diagnosis. Full article

Lentiviral transduction remains the gold standard in adoptive modified cellular therapy, such as CAR-T; however, genome integration is not always desirable, such as when treating non-fatal autoimmune disease or for additional editing steps using CRISPR to produce allogeneic CAR-modified cells. Delivering in vitro-transcribed (IVT) mRNA represents an alternative solution but the labile nature of mRNA has led to efforts to improve half-life and translation efficiencies using a range of approaches including chemical and structural modifications. In this study, we explore the role of N⁶–methyladenosine (m6A) in a CD19-CAR sequence when delivered to T cells as an IVT mRNA. In silico analysis predicted the presence of four m6A consensus (DRACH) motifs in the CAR coding sequence and treating T cells with an inhibitor of the m6A methyltransferase (METTL3) resulted in a significant reduction in CAR protein expression. RNA analysis confirmed m6A bases at three of the predicted sites, indicating that the modification occurs independently of nuclear transcription. Synonymous mutation of the DRACH sites reduced the levels of CAR protein from 15 to >50% depending on the T cell donor. We also tested a panel of CAR transcripts with different UTRs, some containing m6A consensus motifs, and identified those which further improved protein expression. Furthermore, we found that the methylation of consensus m6A sites seems to be somewhat sequence-context-dependent. These findings demonstrate the importance of the m6A modification in stabilising and enhancing expression from IVT-derived mRNA and that this occurs within the cell, meaning targeted in vitro chemical modification during mRNA manufacturing may not be necessary. Full article

B cells are key drivers of immune dysregulation across systemic autoimmune diseases. Among their progeny, plasmablasts occupy a uniquely revealing niche: short-lived, highly proliferative intermediates that mirror real-time B-cell activation. Their appearance in peripheral blood integrates antigenic stimulation, cytokine-driven differentiation, and aberrant germinal-center dynamics, transforming them into sensitive indicators of ongoing immunological activity. This review synthesizes current knowledge on plasmablast biology and highlights disease-specific phenotypes across systemic lupus erythematosus (SLE), primary Sjögren disease (pSjD), IgG4-related disease (IgG4-RD), ANCA-associated vasculitis (AAV), and rheumatoid arthritis (RA). We incorporate molecular insights from single-cell technologies that have uncovered previously unrecognized plasmablast subsets, metabolic states, and interferon-related signatures with prognostic and mechanistic value. Beyond descriptive immunology, plasmablasts are emerging as dynamic biomarkers capable of informing real-time clinical decisions. One of the most robustly supported applications is the prognostic interpretation of plasmablast kinetics following B-cell-depleting therapies, where early reconstitution patterns consistently predict relapse across multiple autoimmune conditions. As clinical immunology shifts from static serological markers toward kinetic, cell-based monitoring, plasmablast quantification offers a path toward precision immune surveillance. Integrating plasmablast dynamics into routine care may ultimately allow clinicians to anticipate disease flares, time therapeutic reinforcements, and transition from reactive management to preventive intervention. Full article

Systemic sclerosis (SSc) is a disease in which malfunctioning immune cells lead to the formation of autoantibodies that damage blood vessels and body tissues. Fibrosis then develops in the affected organs. Its complex pathogenesis involves multiple immune and stromal cell types, soluble mediators, and dysregulated tissue repair, resulting in heterogeneous clinical manifestations and poor prognosis. Current disease-modifying therapies provide only modest benefits, often slowing but rarely reversing disease progression, and are associated with considerable adverse effects. These limitations have spurred the development of cell-based therapeutic strategies aimed at restoring immune tolerance and promoting tissue repair. In this review, we summarize recent advances in hematopoietic stem cell transplantation, mesenchymal stem cell therapy, and adoptive regulatory T cell transfer and highlight the emerging role of chimeric antigen receptor (CAR)-T cell therapy as a transformative approach for SSc. Collectively, these evolving strategies hold the potential to improve survival, achieve durable remissions, and significantly enhance quality of life for patients with SSc. Full article

B-cells and plasmablasts have emerged as central organizers of autoimmune pathogenesis, extending far beyond their classical role as antibody-producing cells to orchestrate immune circuits, tissue microenvironments, and therapeutic trajectories. Advances in single-cell technologies, high-dimensional cytometry, and B-cell receptor sequencing have uncovered a dynamic continuum of B-cell differentiation programs that drive clinical heterogeneity across systemic autoimmune diseases. Plasmablasts, in particular, have gained recognition as highly responsive sensors of immune activation: they expand during flares, encode interferon-driven and extrafollicular responses, and correlate with disease severity. Autoantibody profiles, long viewed as static diagnostic signatures, are now understood as durable molecular footprints of distinct B-cell pathways. In this review, we propose an endotype-based framework integrating B-cell circuits with clinical phenotypes, illustrate therapeutic decision-making through mechanistic case vignettes, and outline future strategies combining immunomonitoring, multi-omics, and precision therapeutics. We further address translational challenges and discuss complementary approaches, including T-cell modulation, FcRn inhibition, and antigen-specific tolerization. Full article