Autoimmunity Reviews[JOURNAL]
Sun
200 papers
SpA in animal models: Unraveling the duality of inflammation and bone formation.
Hilliquin S, Rosine N, Lories R … +1 more , Miceli-Richard C
Autoimmun Rev · 2026 Jun · PMID 42140508 · Publisher ↗
Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory rheumatic diseases affecting the axial skeleton, peripheral joints, and entheses. It is uniquely characterized by the coexistence of inflamm...
Spondyloarthritis (SpA) comprises a heterogeneous group of chronic inflammatory rheumatic diseases affecting the axial skeleton, peripheral joints, and entheses. It is uniquely characterized by the coexistence of inflammation and pathological new bone formation, ultimately leading to ankylosis. Although the precise pathogenic sequence remains incompletely defined, experimental animal models have provided essential mechanistic insights by reproducing key immunological and structural features of the disease. This narrative review synthesizes current knowledge on SpA pathophysiology derived from these models. Rodent models have demonstrated the central role of the IL-23/IL-17 axis. The HLA-B27 transgenic rat and the SKG mouse illustrate how dysregulated type 3 immunity, often amplified by intestinal dysbiosis, drives sustained entheseal inflammation. Non-HLA-B27 inflammatory models, such as proteoglycan-induced arthritis and spontaneous arthritis in DBA/1 mice, have clarified the contribution of osteogenic pathways, particularly Wnt and BMP/TGF-β signaling, in the transition from inflammation to pathological bone formation. Other models highlight the continuum between inflammatory, destructive, and anabolic processes. In transmembrane TNF transgenic mice, severe ossification occurs independently of major erosions. The TNF^ΔARE (TNFTg197) model has been instrumental in establishing a mechanistic link between impaired Wnt inhibition and ankylosis, as pharmacological blockade of Dkk-1 shifts the phenotype from erosive sacroiliitis to complete joint fusion. Together, these models have elucidated the interplay between immune activation, the microbiota, and osteogenic pathways in SpA. They remain indispensable for mechanistic research and therapeutic development and are increasingly integrated with OMICS-based approaches.
Inflammatory biomarkers of atherosclerosis in SLE that may improve SLE-specific cardiovascular risk assessment tools.
De Santis S, Prete M, Leone P … +8 more , Liakouli V, Vomero M, Navarini L, Ruscitti P, Ciccia F, Giacomelli R, Favoino E, Perosa F
Autoimmun Rev · 2026 Jun · PMID 42105836 · Publisher ↗
Cardiovascular (CV) events (CVE) are a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE), and affected patients display a two- to three-fold higher risk than the general population. This incr...
Cardiovascular (CV) events (CVE) are a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE), and affected patients display a two- to three-fold higher risk than the general population. This increased CV risk remains underestimated by traditional CV risk algorithms, which do not account for SLE-specific drivers of accelerated atherosclerosis. The aim of this review is to examine key biomarkers and immune-mediated pathways involved in immune dysregulation and vascular injury. By comparing their contribution to SLE pathogenesis and atherosclerotic plaque development, we have highlighted biomarkers that may be incorporated into more accurate, SLE-specific CV risk assessment tools.
The role of mitophagy in systemic lupus erythematosus.
Wei Y, Zheng J, Tu M … +3 more , Song H, Zhang Y, Ju J
Autoimmun Rev · 2026 Jun · PMID 42105835 · Publisher ↗
Systemic lupus erythematosus (SLE) is a persistent autoimmune condition involving multiple organ systems. It is fundamentally driven by the dysregulation of the immune system. Under this condition, the immune system erro...
Systemic lupus erythematosus (SLE) is a persistent autoimmune condition involving multiple organ systems. It is fundamentally driven by the dysregulation of the immune system. Under this condition, the immune system erroneously targets body tissues and induces a marked inflammatory immune response, ultimately leading to multisystem and multi-organ involvement. Mitophagy is a selective intracellular quality control mechanism that eliminates dysfunctional or redundant mitochondria and is crucial for maintaining cellular homeostasis. In recent years, accumulating research has indicated that dysregulated mitophagy is closely linked to the pathogenesis of SLE and associated organ damage, particularly in lupus nephritis (LN). This review systematically elaborates the molecular regulatory network of mitophagy and its specific roles in immune dysregulation and organ damage in SLE. We further explored therapeutic strategies targeting mitophagy to provide new theoretical foundations and directions for the targeted management of SLE.
Serious infections in antineutrophil cytoplasmic antibody-associated vasculitis: Epidemiology, risk factors, and strategies for prevention.
Chang B, Geetha D, Jayne DRW … +1 more , Kronbichler A
Autoimmun Rev · 2026 Jun · PMID 42105834 · Publisher ↗
Serious infections in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) represent a contributor to morbidity and mortality. Patients are susceptible to both typical and opportunistic infections due...
Serious infections in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) represent a contributor to morbidity and mortality. Patients are susceptible to both typical and opportunistic infections due to immunocompromise resulting from immunosuppressive treatments and disease activity. Over the past decade, studies predominantly in retrospective cohorts have outlined the incidence and nature of serious infections, including organ involvement and pathogens, as well as various risk factors for serious infections. This review summarises the recent literature on serious infections and discusses risk factors for these infections; we have categorised them into baseline characteristics, laboratory values, end-organ damage, and immunosuppressive treatments. It discusses emerging data on the role of reduced glucocorticoid regimens and trimethoprim-sulfamethoxazole prophylaxis in preventing serious infections. Finally, implications on clinical practice and important avenues for future research are discussed.
The application of low-carbohydrate diet in autoimmune diseases: Mechanisms, evidence, and prospects for clinical translation.
Lu MF, Qi XY, Cheng JW … +9 more , Wang MY, Liu SY, Zhang Y, Jiang XJ, Yun Y, Su QY, He PF, Zhang SX, Cheng T
Autoimmun Rev · 2026 Jun · PMID 42061668 · Publisher ↗
Emerging evidence suggests that low-carbohydrate diet (LCD) may exert beneficial effects across multiple autoimmune diseases (AIDs), yet their underlying mechanisms remain insufficiently elucidated and clinical evidence...
Emerging evidence suggests that low-carbohydrate diet (LCD) may exert beneficial effects across multiple autoimmune diseases (AIDs), yet their underlying mechanisms remain insufficiently elucidated and clinical evidence is still limited. This review provides a comprehensive synthesis of mechanistic insights, current clinical findings, and translational perspectives on LCD interventions in AIDs. Mechanistically, LCDs reprogram energy metabolism by shifting immune cell bioenergetics from glycolysis toward fatty acid oxidation and ketone utilization, thereby modulating inflammatory pathways such as NF-κB and the NLRP3 inflammasome. LCDs also reshape the gut microbiota and its metabolites, influencing intestinal barrier integrity and systemic immune responses, while epigenetic regulation-including histone deacetylase inhibition and DNA methylation-further stabilizes regulatory T cell identity and restrains pro-inflammatory gene expression. Clinically, encouraging outcomes have been observed in type 1 diabetes, psoriasis, and multiple sclerosis, whereas evidence in systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease remains scarce and heterogeneous. Importantly, existing data indicate that the optimal dietary pattern may differ across disease contexts, and LCDs are not uniformly superior to alternative dietary strategies. Current challenges include risks of nutrient deficiencies, uncertainties regarding long-term safety, variability in individual responses, and the lack of adequately powered randomized controlled trials. Moving forward, integrative research combining multi-omics, precision nutrition, and disease-specific dietary frameworks is needed to delineate responders, clarify mechanisms, and establish standardized protocols. Collectively, this review provides a structured framework for understanding the mechanistic basis and clinical potential of LCDs in AIDs, and outlines future directions for their safe and effective clinical translation.
Immunodeficiency-autoimmunity syndromes.
Houen G
Autoimmun Rev · 2026 Jun · PMID 42055380 · Publisher ↗
Immunodeficiencies can be grouped into genetically inherited (primary immunodeficiencies), somatic mutation-acquired (secondary genetic immunodeficiencies) and environmentally acquired (secondary immunosuppressions). Suc...
Immunodeficiencies can be grouped into genetically inherited (primary immunodeficiencies), somatic mutation-acquired (secondary genetic immunodeficiencies) and environmentally acquired (secondary immunosuppressions). Such immunodeficiencies and immunosuppressions result in increased infection susceptibility but are also associated with autoimmune diseases to varying degrees. A systematic qualitative analysis of these relationships reveals that primary and secondary immunodeficiencies influencing T and B cell numbers and functions highly predispose to autoimmunity, in close agreement with the defining feature of autoimmune diseases - the presence of autoantibodies and/or autoreactive T cells. Environmentally induced Immunosuppressions have a secondary promoting effect in genetically predisposed individuals. Chronic viral infections, especially with Epstein-Barr virus, appear to play a prominent role together with factors influencing immunity. Due to the interplay of individual immunoprofiles (inherited immune system genes and epigenetic modifications) and individual immunosuppression histories (infections and other environmental exposures), diseases with autoimmune manifestations have the appearance of immunodeficiency-autoimmunity syndromes or auto-immunodeficiency syndromes, which represent a continuum of diseases with overlapping clinical features. Remaining outstanding questions are the molecular details of self-tolerance and the relative contributions of epitope spreading, molecular mimicry and bystander activation.
Dynamic profiling in inflammatory Bowel disease: A manifesto for personalized care.
Privitera G, Allocca M, Antonioli L … +16 more , Calabrese E, Caprioli FA, Castiglione F, Danese S, Daperno M, Dragoni G, Fantini MC, Felice C, Fiorino G, Orlando A, Pradelli L, Ribaldone D, Rizzello F, Savarino EV, Scaldaferri F, Armuzzi A
Autoimmun Rev · 2026 Jun · PMID 42055379 · Publisher ↗
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a heterogeneous chronic condition whose clinical management has been advanced by the availability of molecularly targeted therapie...
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a heterogeneous chronic condition whose clinical management has been advanced by the availability of molecularly targeted therapies. Despite this progress, marked inter- and intra-patient variability limits the effectiveness of a one-size-fits-all treatment approach. Precision medicine is a promising solution, but its implementation in routine care is limited. In this manifesto, we propose a multidimensional conceptual framework for the dynamic clinical profiling of IBD patients to be used in real-world clinical settings. Here, we first review key aspects of gut mucosal immunology, including epithelial-immune-stromal interactions and "angry" immune cells as mechanistic drivers of therapeutic variability. We then discuss five domains that are critical for clinical decision making in IBD: disease complexity (phenotype, history, and prior therapeutic exposure); patient frailty and comorbidities; extraintestinal manifestations; patients' needs and preferences; and sustainability. Integrating these domains into a treat-to-target strategy requires the iterative reassessment of patients and the acknowledgment of the evolving nature of both the disease and the patient. We then provide general recommendations for incorporating these elements into the choice of therapy. Finally, we argue that future IBD care should merge the analysis of composite molecular signatures with holistic, patient-centered, dynamic clinical profiling to guide treatment choice, monitoring, and de-escalation. By reframing personalized medical care as a continuous process - a dynamic profiling - rather than a static assessment, this framework should optimize therapeutic outcomes, enhance patients' quality of life, and improve the sustainability of IBD care.
Bispecific T-cell engagers in autoimmune diseases: mechanisms of action, clinical evidence challenges, and therapeutic perspectives.
Larue M, Bitoun S, Zuber J … +2 more , Michel M, Talbot A
Autoimmun Rev · 2026 Jun · PMID 42002248 · Publisher ↗
Bispecific T-cell engagers (TCEs) represent a new generation of immunotherapies designed to redirect cytotoxic T lymphocytes toward specific cellular targets, particularly B cells and their differentiated progeny. Initia...
Bispecific T-cell engagers (TCEs) represent a new generation of immunotherapies designed to redirect cytotoxic T lymphocytes toward specific cellular targets, particularly B cells and their differentiated progeny. Initially developed in hematology for the treatment of malignant B-cell and plasma-cell disorders, TCEs are now gaining growing interest as potential therapies for severe or refractory autoimmune diseases. By simultaneously binding CD3 on T cells and antigens such as CD19, CD20, or BCMA (B-cell maturation antigen) on B-lineage cells, TCEs induce the targeted elimination of autoreactive B cells and plasma cells responsible for autoantibody production. This approach combines the depth of immune depletion achieved with cellular therapies and the controllability of monoclonal antibodies, offering the potential for rapid, profound, and durable immunomodulation. However, it also raises important questions regarding safety, feasibility, and cost. Compared with CAR-T cell therapies, TCEs offer a more accessible and immediately deployable strategy, while potentially achieving comparable levels of B-cell and plasma-cell depletion, though with shorter exposure and possibly reduced long-term persistence. This review provides an integrated overview of mechanistic, preclinical, and emerging clinical data on the use of TCEs in autoimmune diseases, and discusses their therapeutic potential, and limitations in this evolving field.
Innate immunity and biomarkers of multiple sclerosis relapse versus remission.
Karadeniz M, Wesselingh R, Jayakrishnan PC … +4 more , Sequeira RP, Van Der Walt A, Butzkueven H, Monif M
Autoimmun Rev · 2026 Jun · PMID 42000092 · Publisher ↗
Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease presenting most commonly in its relapsing and remitting form, whereby a relapse is defined as an acute exacerbation of disease activity associated w...
Multiple sclerosis (MS) is a neurodegenerative and inflammatory disease presenting most commonly in its relapsing and remitting form, whereby a relapse is defined as an acute exacerbation of disease activity associated with worsening disability. Relapse diagnosis is impeded by its heterogeneous presentation, limited detectability on magnetic resonance imaging and 'pseudo-relapse' which occurs due to factors unrelated to MS itself such as infection. Currently, we do not have easily accessible biomarkers that can distinguish relapse from remission. The diagnosis is generally made on clinical grounds as per the discretion of a neurologist and relapse treatment constitutes usage of high dose corticosteroids which may not provide long term benefit. Additionally, the recurrent usage of high dose corticosteroids is associated with a myriad of side effects and their mechanism of action is not targeted. To improve diagnostic and treatment strategies for MS relapse, we must first understand the underlying biology involved. Most literature in this field focuses on lymphocytes, overlooking innate immunity. Indeed, all the current disease modifying therapies in MS target lymphocytes. However, there is increasing evidence for the role of innate immune cells in MS disease activity. This review will discuss MS disease, relapse presentation, treatment strategies, the cellular composition of different lesion types and consider current biomarkers of disease activity versus disease stability. With a focus on innate immunity, we hope to provide new insight into future novel biomarkers to capture MS disease activity.
Anti-CD52 therapy of rheumatic diseases: Revisited in the era of immune reset.
Hassan F, Isaacs JD, Naffaa ME
Autoimmun Rev · 2026 May · PMID 41956272 · Publisher ↗
Alemtuzumab is a humanized monoclonal antibody targeting CD52, a glycosylphosphatidylinositol-anchored surface antigen broadly expressed on lymphocytes and other immune cells. Although currently approved for multiple scl...
Alemtuzumab is a humanized monoclonal antibody targeting CD52, a glycosylphosphatidylinositol-anchored surface antigen broadly expressed on lymphocytes and other immune cells. Although currently approved for multiple sclerosis and used in selected transplantation settings, alemtuzumab was among the earliest lymphocyte-depleting biologics explored across a wide spectrum of autoimmune rheumatic diseases. With renewed interest in deep immune-depleting strategies, including CAR-T cells and bispecific T-cell engagers, revisiting the immunobiology and clinical experience of alemtuzumab is timely. This review summarizes current knowledge of CD52 structure, expression, and immunological function, highlighting its dual role as both a co-stimulatory and immunoregulatory molecule. We examine the mechanisms underlying alemtuzumab-induced lymphocyte depletion, subsequent immune reconstitution, and the paradoxical development of secondary autoimmunity. Clinical evidence for alemtuzumab use in rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, vasculitis, idiopathic inflammatory myopathies, ocular inflammatory disease, and Behçet's syndrome, is reviewed, with emphasis on efficacy, durability of response, and safety outcomes. Across multiple refractory disease settings, alemtuzumab has demonstrated the capacity to induce rapid clinical improvement and, in some cases, prolonged drug-free remission. However, treatment is limited by risks of infection, delayed immune reconstitution, and immune dysregulation. We conclude that alemtuzumab remains a potent immunomodulatory option in selected refractory rheumatic diseases, provided that careful patient selection, cautious monitoring, and long-term follow-up are implemented.
Effects of vitamin D supplementation on patients with systemic lupus erythematosus: A systematic review and meta-analysis.
Lu J, Zhu Q, Yu J … +4 more , Tan Z, Kang Y, Sun Q, Zhao T
Autoimmun Rev · 2026 May · PMID 41951148 · Publisher ↗
BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease frequently associated with vitamin D insufficiency. Vitamin D supplementation has been proposed as a potential adjunctive therapeutic strateg...
BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease frequently associated with vitamin D insufficiency. Vitamin D supplementation has been proposed as a potential adjunctive therapeutic strategy for SLE. OBJECTIVE: To evaluate the effects of vitamin D supplementation on disease activity and related clinical outcomes in patients with SLE. METHODS: A systematic search of PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wanfang Data was conducted from inception to March 2025. Randomized controlled trials (RCTs) were included. Data extraction and statistical analyses were performed using Review Manager 5.3 and Stata/MP 16.0. Risk of bias was assessed using the Cochrane Collaboration tool. RESULTS: 10 RCTs involving 847 participants were included. Vitamin D supplementation significantly improved serum 25(OH)D status (SMD = 3.46, p < 0.001) and reduced disease activity in SLE (SMD = -0.54, p < 0.001). Significant improvements were also observed in complement component C3 (MD = 14.49, p = 0.03) and C4 (SMD = 2.08, p = 0.04). No significant effects were found for erythrocyte sedimentation rate (ESR) (MD = -10.19, p = 0.24) or fatigue severity (SMD = -1.77, p = 0.07). Anti-dsDNA antibody levels showed no significant change (MD = 7.78, p = 0.82), while positivity rates were significantly improved (RR = 5.44, p = 0.001). CONCLUSION: Vitamin D supplementation may reduce disease activity and improve complement levels in SLE, but evidence for other outcomes remains inconsistent, warranting further high-quality trials.
Predicting the course: Real-world trajectories toward minimal disease activity in psoriatic arthritis.
Fatica M, Perrotta FM, Conigliaro P … +2 more , Chimenti MS, Lubrano E
Autoimmun Rev · 2026 May · PMID 41946409 · Publisher ↗
OBJECTIVES: To investigate real-world trajectories toward minimal disease activity (MDA) in psoriatic arthritis (PsA) patients starting their first biologic or targeted synthetic DMARD (bDMARD/tsDMARD) and identify basel...
OBJECTIVES: To investigate real-world trajectories toward minimal disease activity (MDA) in psoriatic arthritis (PsA) patients starting their first biologic or targeted synthetic DMARD (bDMARD/tsDMARD) and identify baseline predictors of each trajectory. METHODS: This is a retrospective observational study of 289 patients with PsA (CASPAR criteria) from two Italian tertiary centers (2020-2023), all not in MDA at baseline and with ≥24 months follow-up. MDA status was assessed every 6 months. Patients were categorized into four trajectories based on MDA achievement and maintenance: Super Responders, Delayed Responders, Fluctuating Responders, and Non-Responders. Clinical features and treatment patterns were compared, and multivariable logistic regression identified predictors of trajectory membership. RESULTS: Mean age was 52.4 ± 12.3 years, disease duration 7.3 ± 5.1 years, and baseline DAPSA 23.4 ± 11.6. Most patients started TNF-α inhibitors (70.9%), and 60.9% achieved MDA at 24 months. Trajectory distribution was: Super Responders (23.2%), Delayed Responders (21.8%), Fluctuating Responders (37.0%), and Non-Responders (18.0%). Super Responders were predominantly male, with lower baseline disease activity and fewer metabolic comorbidities. Non-Responders were more often female, overweight/obese, and had higher fibromyalgia rates. Predictors of Super Responder status included male sex (OR 2.26) and absence of metabolic comorbidities (OR 2.29); higher baseline DAPSA decreased odds (OR 0.92). Predictors of Non-Responder status were female sex (OR 2.56), fibromyalgia (OR 5.30), and overweight/obesity (OR 2.04). No significant predictors of the other trajectory groups were found. CONCLUSIONS: Patients with PsA initiating bDMARD/tsDMARDs exhibit diverse disease trajectories. Identified predictors may inform trajectory-based risk stratification and optimize treat-to-target approaches.
Effects of biologics and small-molecule inhibitors on lipid profiles in patients with psoriasis or psoriatic arthritis: An analysis of current evidence.
Zhang M, Gao P, Li Y … +10 more , Cao R, Zhou X, Liu L, Wu H, Wang J, Cai X, Hong S, Sun X, Su Y, Li X
Autoimmun Rev · 2026 May · PMID 41935726 · Publisher ↗
IMPORTANCE: Available evidence reveals markedly divergent metabolic signatures across biologics and small-molecule inhibitors, highlighting the need for further investigations. OBJECTIVE: To address this knowledge gap, w...
IMPORTANCE: Available evidence reveals markedly divergent metabolic signatures across biologics and small-molecule inhibitors, highlighting the need for further investigations. OBJECTIVE: To address this knowledge gap, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies in patients with psoriasis or psoriatic arthritis (PsA) to quantify the short- and long-term effects of targeted therapies on lipid profiles. EVIDENCE REVIEW: PubMed, Embase, and Cochrane databases were searched for RCTs and observational studies published through July 25, 2025. Eligible randomized RCTs were evaluated using the Cochrane Risk of Bias tool, while nonrandomized studies were assessed using the Methodological Index for Non-Randomized Studies. All lipid effect estimates were derived from within-group pre-to-post changes in patients with psoriasis or PsA. FINDINGS: Thirty-six articles involving 21,477 patients with psoriasis and 3098 patients with PsA (total 24,575) across seven targets were analyzed. The long-term use of Janus kinase inhibitors (JAKi) significantly increases total cholesterol (TC; weighted mean difference [WMD] = 7.03; 95% confidence interval [CI] = 1.22, 12.84), triglyceride (TG; WMD = 19.98; 95% CI = 13.82, 26.14), high-density lipoprotein cholesterol (HDL-c; WMD = 6.87; 95% CI = 4.38, 9.36), and low-density lipoprotein cholesterol (LDL-c; WMD = 12.37; 95% CI = 7.24, 17.50) levels. Long-term tumor necrosis factor alpha inhibitors (TNFi) significantly lowers TC (WMD = -8.40; 95% CI = -15.21, -1.60), TG (WMD = -15.22; 95% CI = -21.92, -8.51), and LDL-c (WMD = -10.61; 95% CI = -16.77, -4.45) levels while raising HDL-c (WMD = 4.13; 95% CI = 1.23; 7.03) levels. Long-term interleukin-17 A inhibitors significantly increases TG (WMD = 7.31; 95% CI = 3.17, 11.46) levels, whereas IL-23p19 inhibitors yield the opposite effect (WMD = -32.08; 95% CI = -51.87, -12.30). CONCLUSIONS AND RELEVANCE: Our data underscore the need for routine lipid monitoring during TNF-α- and JAK-targeted therapy in patients with psoriasis or PsA. Due to the limitations of our analysis, well-designed prospective trials with extended follow-up periods are warranted to validate and refine these observations.
The role of myeloid-derived suppressor cells in Sjögren's disease.
Jin L, Yang C, Gan J … +5 more , Wan Z, Liu Y, Wong VKW, Li C, Wang Y
Autoimmun Rev · 2026 May · PMID 41916441 · Publisher ↗
Sjögren's Disease (SjD) is a chronic autoimmune disease characterized by exocrine glandular lymphocyte infiltration and functional damage, with a complex pathogenesis and immune cell imbalance as a key driver. Myeloid-de...
Sjögren's Disease (SjD) is a chronic autoimmune disease characterized by exocrine glandular lymphocyte infiltration and functional damage, with a complex pathogenesis and immune cell imbalance as a key driver. Myeloid-derived suppressor cells (MDSCs), as heterogeneous immature myeloid cells, play an immunosuppressive function by secreting molecules such as arginase 1, nitric oxide, and reactive oxygen species, and play a dual role in tumor immune escape and autoimmune disease regulation. In recent years, studies have shown that the frequency of MDSCs increases abnormally in SjD patients and animal models, but their physiological function changes dynamically. For instance, MDSCs show immunosuppressive activity in the early stage of the disease, and in the late stage, their immunosuppressive property is impaired or even transformed into a pro-inflammatory phenotype and are therefore involved in the pathogenesis of SjD by regulating the balance of T cell subsets and the secretion of inflammatory factors. Nevertheless, the pathogenic role of MDSC in SjD is not fully understood, and some controversy remains, as well as many unanswered questions. This review summarizes the most recent literature on MDSCs in SjD, systematically reviews the phenotypic characteristics, metabolic and signaling remodeling mechanisms, treatment strategies associated with MDSCs, regulation between MDSCs and key immune cells and role of MDSCs in systemic manifestations in SjD, and discusses the relationship between MDSCs and SjD.
The risk of allergy in patients with IgG4-related disease: A systematic review and meta-analysis.
Li Z, Zhang J, Xu H … +3 more , Feng F, Zhang W, Li Y
Autoimmun Rev · 2026 May · PMID 41912044 · Publisher ↗
BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated condition characterized by multi-organ involvement. Substantial evidence suggests a close link between allergy and IgG4-RD, supported by the high prevalenc...
BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated condition characterized by multi-organ involvement. Substantial evidence suggests a close link between allergy and IgG4-RD, supported by the high prevalence of allergic comorbidities in patients and shared immunological features such as eosinophilia and elevated serum IgE. However, the precise mechanistic connections and potential causal relationship between allergy and IgG4-RD remain unclear. This study aimed to systematically quantify the proportion of IgG4-RD patients presenting with allergy, eosinophilia, and hyper-IgE. METHODS: A comprehensive literature search of the PubMed, Web of Science, EMBASE, and the Cochrane Library was conducted up to August 7, 2025. Studies meeting the inclusion criteria were reviewed. Meta-analysis was performed using both random- and fixed-effects models. RESULTS: The search identified 1884 studies, of which 32 were included in the analysis. Among these, 30 studies contributed to the allergy analysis, 15 to eosinophilia, and 9 to hyper-IgE. The meta-analysis showed that the pooled proportion of IgG4-RD patients with allergy was 0.44 (95% CI, 0.39, 0.49; p < 0.01; n = 8233). The pooled proportion with eosinophilia was 0.22 (95% CI, 0.18, 0.26; p < 0.01; n = 4376), and with hyper-IgE was 0.73 (95% CI, 0.63, 0.83; p < 0.01; n = 2353). CONCLUSIONS: A notable proportion of IgG4-RD patients exhibit allergy, eosinophilia, and hyper-IgE. The frequent co-occurrence of these features highlights the need to investigate the underlying mechanisms, clarify the causal relationship between allergy and IgG4-RD, and provide further insights for both mechanistic research and clinical management of IgG4-RD, especially through well-controlled comparative studies to establish whether these features are truly more prevalent in IgG4-RD than in the general population or other conditions.
Prevalence and clinical significance of anti-NOR90 antibodies in systemic sclerosis: Results from a multicentre cohort and systematic literature review.
Narváez J, González-Gay MÁ, Morandeira F … +9 more , Dueñas M, Roig-Kim M, Aguilar-Coll M, de Daniel-Bisbe L, Alfranca A, Valero-Martínez C, Vicente-Rabaneda EF, Nolla JM, Castañeda S
Autoimmun Rev · 2026 May · PMID 41903744 · Publisher ↗
OBJECTIVE: To evaluate the prevalence and clinical associations of anti-Nucleolar Organizer Region 90 (anti-NOR90) antibodies in patients with systemic sclerosis (SSc). METHODS: We conducted a cross-sectional study of an...
OBJECTIVE: To evaluate the prevalence and clinical associations of anti-Nucleolar Organizer Region 90 (anti-NOR90) antibodies in patients with systemic sclerosis (SSc). METHODS: We conducted a cross-sectional study of anti-NOR90-positive SSc patients from two tertiary hospitals, using the EUROLINE SSc profile kit and including only patients with repeated moderate or strong positivity. A comparative analysis was performed between patients with and without anti-NOR90 antibodies. Further, we performed a systematic literature search to summarise published evidence on anti-NOR90 antibodies in SSc. RESULTS: We identified 21 anti-NOR90-positive patients, with a prevalence of 5.5% and 3.0% in each center. Fourteen patients (67%) were positive for at least one SSc-criteria autoantibody (anticentromere or anti-RNA polymerase III). Compared with 293 anti-NOR90-negative patients, anti-NOR90-positive cases had significantly less microvascular involvement, with fewer telangiectasias (p = 0.005) and no digital ulcers (p = 0.032), as well as lower frequencies of calcinosis (p = 0.018), gastrointestinal involvement (gastric, p = 0.024; intestinal, p = 0.029), and pulmonary arterial hypertension (p = 0.012). No significant differences were observed in other disease domains. In multivariable analysis, anti-NOR90 positivity remained independently associated with a lower prevalence of intestinal involvement (OR 0.332, 95% CI 0.119 to 0.931; p = 0.036) and composite microvascular involvement, defined as telangiectasias and/or digital ulcers (OR 0.285, 95% CI 0.113 to 0.719; p = 0.008). The systematic literature review confirmed that anti-NOR90 antibodies are uncommon (2.41%) and associated with a predominantly female phenotype, lower frequencies of diffuse cutaneous SSc, digital ulcers, arthritis, myopathy, and intestinal involvement, as well as frequent coexistence with other SSc-related autoantibodies. CONCLUSION: Anti-NOR90 antibodies identify an infrequent, predominantly female subset of patients that appears to be associated with milder microvascular disease and lower frequency of intestinal symptoms.
The BAFF/APRIL system at the crossroads of B cell memory and autoimmune relapse: Implication into the therapeutic strategies.
Liao C, Chen Y, Ye C … +7 more , Lin S, Bai L, Zhang Z, Sun W, Hu Z, Cai S, Dong L
Autoimmun Rev · 2026 May · PMID 41903743 · Publisher ↗
B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) exert their functions by engaging distinct receptors, B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI), and...
B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) exert their functions by engaging distinct receptors, B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI), and BAFF receptor (BAFFR), thereby regulating the differentiation and survival of specific B cell subsets. Humoral immune memory relies on two complementary reservoirs, long-lived plasma cells (LLPCs) and memory B cells (MBCs). They can be categorized from a developmental perspective into low-affinity, short-lived cells generated in a germinal center (GC)-independent manner, and high-affinity, long-lived cells that require GC reactions. As a key survival factor for B cells, the BAFF/APRIL system plays a critical regulatory role in maintaining these compartments. The memory reservoirs particularly in autoimmune disorders where B cells act as central pathogenic drivers, sustain autoreactive antibody pools and largely contribute to disease relapse. Following the success of BAFF/APRIL system targeted biologics, such as belimumab and telitacicept, and with BCMA-directed chimeric antigen receptor T (CAR-T) cell therapy recently showing remarkable efficacy in autoimmune diseases, novel treatment avenues have emerged for cases resistant to conventional B cell depletion strategies. We now recognize that while conventional B cell depletion effectively reduces the circulating B cells to achieve rapid disease control, therapeutic targeting of the BAFF/APRIL system addresses the survival of long-lived subsets such as LLPCs, thereby filling the gap left by depletion strategies and partially contributes to sustained immunological control. These distinctions highlight the rationale for sequential therapeutic strategies, reinforcing the translational potential of precision medicine in autoimmune disease management.
Contribution of intestinal mucosa to the disease mechanisms of Spondyloarthritis: Unlocking new insights through bioengineered tissue models.
Natalello G, De Lorenzis E, D'Agostino MA … +4 more , Langella P, Breban M, Cherbuy C, Bazin T
Autoimmun Rev · 2026 May · PMID 41895459 · Publisher ↗
Spondyloarthritis (SpA) represents a spectrum of chronic inflammatory rheumatic disorders with similar articular and extra-articular features and a complex pathogenesis stemming from the interplay between genetics, envir...
Spondyloarthritis (SpA) represents a spectrum of chronic inflammatory rheumatic disorders with similar articular and extra-articular features and a complex pathogenesis stemming from the interplay between genetics, environmental triggers, and immune system dysregulation. The significant prevalence of SpA and its onset in the working age population place a considerable burden on healthcare systems. Furthermore, many patients fail to achieve optimal treatment outcomes and present physical and psychological distress, underscoring the need for improved therapeutic approaches. The emerging concept of the gut-joint axis suggests that disturbances at the intestinal mucosal interface and microbiota level may initiate or amplify inflammatory responses, contributing to the clinical expression of SpA. Unfortunately, traditional pre-clinical in vitro and animal models have intrinsic limitations in replicating the intricate human intestinal mucosa anatomo-functional network, thus constraining translational research. Bioengineered tissue models (BTMs), including organoids, organs-on-a-chip (OoCs), and co-culture systems integrating human-derived cells, offer novel platforms that better mimic human tissue architecture and physiological responses. These advanced models hold promise in elucidating multifactorial disease mechanisms and expediting drug development, potentially facilitating personalized and more effective therapies. This article presents a narrative review of current knowledge about perturbations at the level of human intestinal mucosa during SpA and aims to critically synthesize the conceptual and experimental advances in the emerging field of BTMs to support future translational research in this field.
Expert perspectives on Myalgic encephalomyelitis/chronic fatigue syndrome - Insights from the 3 International Conference of the Charité Fatigue Center.
Fehrer A, Windzio L, Schoening S … +40 more , Steiner S, Aschenbrenner AC, Babel N, Behrends U, Bellmann-Strobl J, Cammà G, Cash A, Doehner W, den Dunnen J, Fluge Ø, Franke C, Hoffmann K, Kedor C, Kim L, Löhden W, Mella O, Mihatsch LL, Peluso MJ, Puta C, Putrino D, Ramoji A, Sato W, Sawitzki B, Schlieper G, Schoenfeld Y, Seifert M, Sigurdsson F, Slaghekke A, Sommerfelt K, Sotzny F, Stein E, Steinacker JM, Stingl M, Systrom DM, Tronstad KJ, Wirth K, Wörmann B, Wüst RCI, Yamamura T, Scheibenbogen C
Autoimmun Rev · 2026 May · PMID 41895458 · Publisher ↗
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognit...
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystemic disorder mostly triggered by viral infections, with core symptoms including post-exertional malaise (PEM), fatigue, pain, and cognitive dysfunction. Its prevalence has increased significantly in the context of the coronavirus disease 2019 (COVID-19) pandemic. Despite its severity and impact on patients' quality of life, ME/CFS remains poorly understood. On May 12 and 13, 2025, the 3 International Conference hosted by the Charité Fatigue Center brought together nearly 200 researchers from various disciplines on-site, and around 3,700 participants online to discuss recent advances in ME/CFS research, diagnostics, clinical care, and therapeutic trials. The program featured 33 lectures by international experts on key topics such as post-COVID syndrome (PCS), care structures, and pathophysiological mechanisms including cardiovascular dysregulation, immune dysregulation, autoimmune mechanisms, and metabolic dysfunction. In addition, results from clinical trials addressing disease mechanisms, including those specifically targeting autoantibodies, were presented. While public awareness and funding opportunities have increased in the wake of the pandemic and the emergence of PCS, ME/CFS remains severely underresearched. Sustained and adequately funded research efforts are urgently required to advance understanding, identify diagnostic markers, and develop targeted therapeutic interventions.
Isolated antineutrophil cytoplasmic antibody-associated interstitial lung disease: A systematic review of an emerging condition.
Narváez J, Maymó P
Autoimmun Rev · 2026 Apr · PMID 41871820 · Publisher ↗
OBJECTIVE: To summarise the clinical characteristics, radiological and histopathological features, treatment approaches, and outcomes of isolated antineutrophil cytoplasmic antibody-associated interstitial lung disease (...
OBJECTIVE: To summarise the clinical characteristics, radiological and histopathological features, treatment approaches, and outcomes of isolated antineutrophil cytoplasmic antibody-associated interstitial lung disease (ANCA-ILD). METHODS: A systematic literature review conducted according to the PRISMA statement. RESULTS: Twenty-four studies comprising 794 patients were included. Isolated ANCA-ILD predominantly affected older adults, between 50 and 70 years of age, with a slight male predominance (57%). MPO-ANCA positivity was observed in approximately 70% of patients, whereas PR3-ANCA positivity accounted for 10-15%. Fibrotic patterns predominated, with usual interstitial pneumonia (UIP) or UIP-like changes reported in 45-65% of cases, followed by NSIP in 15-30%. Glucocorticoids were prescribed in 58% of patients, immunosuppressive therapies in 31%, and antifibrotic treatment in approximately 26% of those reported in more recent cohorts. Functional decline occurred in approximately 30-50% of patients, and radiological progression in 30-45%. Acute exacerbations were reported in 19-25%, and up to 40% fulfilled criteria for progressive pulmonary fibrosis during follow-up. Progression to systemic ANCA-associated vasculitis (AAV) occurred in approximately 10-40% of cases, with timing ranging from the first year to several years later. This evolution occurred mainly toward microscopic polyangiitis (MPA), whereas granulomatosis with polyangiitis was infrequent, representing ≤10-20% of cases. Survival was generally comparable to ANCA-negative idiopathic interstitial pneumonia and AAV-ILD. CONCLUSION: Isolated ANCA-ILD is an emerging, increasingly recognised fibrotic interstitial lung disease phenotype characterised by frequent MPO-ANCA positivity and two partly independent trajectories: (1) an IPF-like fibrotic course and (2) progression to systemic AAV, most commonly MPA.
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