Autoimmunity Reviews[JOURNAL]
Sun
200 papers
Decoding gut microbiome alterations in celiac disease: Implications for pathogenesis and treatment.
Fousekis F, Lianos GD, Stavropoulou E … +4 more , Patrikiou E, Vradelis S, Cassimos D, Tsigalou C
Autoimmun Rev · 2026 Jul · PMID 42386020 · Publisher ↗
Celiac disease (CD) is a chronic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals and characterized by intestinal inflammation, epithelial damage, and loss of immune tolerance....
Celiac disease (CD) is a chronic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals and characterized by intestinal inflammation, epithelial damage, and loss of immune tolerance. While a strict lifelong gluten-free diet (GFD) remains the cornerstone of treatment, accumulating evidence indicates that it does not consistently restore gut microbiome composition or function, and many patients experience persistent symptoms despite good dietary adherence. The gut microbiome has emerged as a key modulator of immune homeostasis, intestinal barrier integrity, and gluten metabolism, implicating microbial dysbiosis in both the initiation and progression of CD. Alterations in microbial composition and metabolic activity have been documented in genetically at-risk individuals prior to disease onset, in patients with active disease, and in treated patients on a GFD, suggesting a potential role of the microbiome in early pathogenesis, disease heterogeneity, and symptom persistence. In this review, we summarize current evidence on the bidirectional interactions between the gut microbiome and CD, including microbial-mediated gluten degradation, microbiome signatures associated with genetic susceptibility and disease activity, and the effects of a GFD on microbial ecology. We further discuss emerging strategies aimed at modulating the gut microbiome, including probiotics, prebiotics, postbiotics and precision probiotics, as potential adjunctive therapeutic approaches. A better understanding of microbiome-host interactions in CD may support the development of personalized therapeutic strategies that go beyond gluten avoidance and aim to restore microbial balance and immune regulation, thereby improving long-term outcomes.
Rethinking immunosuppression in limited cutaneous systemic sclerosis. The lcSSc conundrum; pros and cons for a timely immunosuppressive treatment.
Batani V, Del Galdo F, Matucci-Cerinic M … +1 more , Allanore Y
Autoimmun Rev · 2026 Jun · PMID 42372841 · Publisher ↗
The use of immunosuppressants (IS) has dramatically changed the management of autoimmune diseases. In systemic sclerosis (SSc), randomized controlled trials and international recommendations support IS use in patients wi...
The use of immunosuppressants (IS) has dramatically changed the management of autoimmune diseases. In systemic sclerosis (SSc), randomized controlled trials and international recommendations support IS use in patients with rapidly progressive diffuse disease or interstitial lung disease (ILD). However, their role in the limited cutaneous systemic sclerosis (lcSSc) subset remains controversial. This article discusses arguments both in favor of and against the use of IS in lcSSc, integrating clinical evidence, pathophysiological insights, and registry data, while acknowledging the limitations inherent to observational findings. Overall, the available evidence suggests that reliance on skin subset classification alone may be insufficient to guide treatment decisions, and highlights the potential value of more refined, biology-informed approaches. However, further prospective validation is required before such strategies can be translated into clinical practice.
Kidney failure in patients with ANCA-associated vasculitis: A systematic review of outcomes.
Kronbichler A, Ramirez de Arellano A, Cattin J … +1 more , Hunt B
Autoimmun Rev · 2026 Jun · PMID 42349595 · Publisher ↗
INTRODUCTION: Kidney involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) significantly increases morbidity and risk of mortality, particularly with progression to end-stage kidney disease (ESKD...
INTRODUCTION: Kidney involvement in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) significantly increases morbidity and risk of mortality, particularly with progression to end-stage kidney disease (ESKD). This review focused on the cumulative incidence of ESKD in patients with AAV and assessed how changes in estimated glomerular filtration rate (eGFR) impact the risk of developing ESKD. METHODS: Literature searches were performed in the PubMed, EMBASE and Cochrane Library databases, focusing on studies published in 2019-2024 with at least 100 participants and a minimum follow-up of 3 years. Combined estimates of the cumulative incidence of ESKD and hazard ratios (HRs) quantifying the relationship between eGFR and ESKD risk were calculated. RESULTS: A total of 49 studies (19,301 patients) reported the incidence of ESKD, while 19 studies (4513 patients) reported the relationship between eGFR and ESKD risk. ESKD incidence ranged from 2.9 to 59.6% at 1 year of follow-up, and from 9.4 to 51.4% at 10 years. The meta-analysis found that ESKD incidence was 14.2% and 24.8% at 1 and 10 years of follow-up, respectively, and that 1 mL/min/1.73 m higher eGFR at diagnosis and at 6 months after diagnosis were associated with 5-6% and 7-8% reductions in ESKD risk, respectively. CONCLUSIONS: This review indicates that patients with AAV remain at high risk of ESKD, with lower eGFR at diagnosis and at 6 months after diagnosis associated with poorer kidney outcomes. However, the pooled estimates should be used with caution, given the high heterogeneity in patient characteristics across studies.
The role of antimicrobial peptides in rheumatoid arthritis: From mucosal predisposition to chronic synovitis.
Anania JC, Smith CB, Edwards CJ
Autoimmun Rev · 2026 Jun · PMID 42331306 · Publisher ↗
Antimicrobial peptides (AMPs) play many roles in immune regulation, integrating direct antimicrobial activity with potent immunomodulatory functions to coordinate host defence. However, these same signals can become mala...
Antimicrobial peptides (AMPs) play many roles in immune regulation, integrating direct antimicrobial activity with potent immunomodulatory functions to coordinate host defence. However, these same signals can become maladaptive and contribute to the development and persistence of chronic inflammatory diseases such as rheumatoid arthritis (RA). In the inflamed joint, AMPs can disrupt tissue architecture, activate resident and infiltrating immune cells through multiple mechanisms, such as neutrophil extracellular trap formation, and may themselves serve as autoantigens, thereby amplifying pathogenic immune responses. Conversely, the pleiotropic nature of AMPs also presents opportunities for their exploitation as biomarkers of disease activity or as direct therapeutic agents to treat RA. This review examines the contributions of human AMPs to RA pathogenesis, with a particular focus on their actions within the synovial microenvironment, including both fibroblast populations and infiltrating immune cells during chronic inflammation.
The role of short-chain fatty acids as key mediators of gut microbiota - host crosstalk in thyroid diseases.
Shen S, Zhang J, Qi X
Autoimmun Rev · 2026 Jun · PMID 42320851 · Publisher ↗
The gut-thyroid axis has emerged as a pivotal area of research in endocrinology. Growing evidence suggests that gut microbiota (GM) dysbiosis is implicated in the pathogenesis of thyroid diseases. Short-chain fatty acids...
The gut-thyroid axis has emerged as a pivotal area of research in endocrinology. Growing evidence suggests that gut microbiota (GM) dysbiosis is implicated in the pathogenesis of thyroid diseases. Short-chain fatty acids (SCFAs), key microbial metabolites, are proposed as critical mediators in this interplay, but a comprehensive synthesis of their roles is needed. This review provides an overview of the mechanisms and therapeutic potential of SCFAs in thyroid diseases. Patients with thyroid diseases commonly exhibit gut microbiota dysbiosis, characterized by reduced SCFA-producing bacteria and decreased systemic SCFA levels. Mechanistically, SCFAs regulate immune and metabolic homeostasis through G protein-coupled receptor signaling, histone deacetylase inhibition, mitochondrial metabolism, mTOR-S6K signaling, and intestinal barrier protection. Their deficiency may disrupt immune tolerance, promoting autoimmunity and tumor progression. However, current research remains largely correlative, with insufficient mechanistic evidence. SCFAs are central to gut-thyroid crosstalk. Targeting SCFA pathways through probiotics, prebiotics, or microbiota transplantation represents a promising therapeutic frontier. Future research must prioritize establishing causality using advanced models and validating these approaches in rigorous clinical trials to pave the way for personalized microbiome-based therapies for thyroid diseases.
Intermittent hydrarthrosis (periodic synoviosis): A narrative review.
de Carvalho JF, Shoenfeld Y
Autoimmun Rev · 2026 Jun · PMID 42289262 · Publisher ↗
Intermittent hydrarthrosis (IH), also termed periodic synoviosis or periodic benign synovitis, is a rare cause of recurrent, self-limited joint effusion-most frequently involving the knee-with striking periodicity and co...
Intermittent hydrarthrosis (IH), also termed periodic synoviosis or periodic benign synovitis, is a rare cause of recurrent, self-limited joint effusion-most frequently involving the knee-with striking periodicity and complete intercritical recovery. Despite being recognized for decades, IH remains underdiagnosed and is often mistaken for palindromic rheumatism, crystal-induced arthritis, septic arthritis, proliferative synovial disorders, and autoinflammatory syndromes. Historical descriptions emphasized a benign, non-destructive course, minimal systemic inflammation, and a lack of specific biomarkers [1, 2]. More recent reports suggest that, in a subset of patients, IH may overlap with autoinflammatory mechanisms, including associations with MEFV mutations and clinical responses to colchicine or IL-1 blockade [3-6]. This narrative review synthesizes available evidence on terminology, clinical spectrum, diagnostic work-up, hypothesized pathophysiology, differential diagnosis, and therapeutic options, and proposes a pragmatic approach for clinicians.
Unraveling giant cell arteritis: From immunopathology to emerging targeted therapies (2026 update).
Cayrou C, Gallet F, Ly K … +3 more , Fauchais AL, Bouanat S, Parreau S
Autoimmun Rev · 2026 Jun · PMID 42288301 · Publisher ↗
Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly mainly because of cellular senescence and "inflammaging" It results from granulomatous inflammation primarily affecting the aorta and its m...
Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly mainly because of cellular senescence and "inflammaging" It results from granulomatous inflammation primarily affecting the aorta and its major branches. Recent advances highlight vascular dendritic cell (DC) activation via TLRs as the initiating event, leading to chemokine-mediated recruitment and polarization of CD4+ T cells mainly into Th1/Th17 subsets. These effector T cells drive monocyte differentiation into pro-inflammatory macrophages and giant cell formation, with subsequent matrix metalloproteinase production causing elastic lamina destruction and vascular remodeling. This vascular remodeling involves activation of endothelial cells, fibroblasts and smooth muscle cells followed by a differentiation in myofibroblast in the intima. Neutrophils may play an underestimated role. Current treatments remain limited to glucocorticoids, methotrexate and tocilizumab though relapse rates remain high. This narrative review synthesizes the DC-T-macrophage-fibroblast cascade and evaluates emerging biologics: abatacept showed phase 2 efficacy but real-world inferiority to tocilizumab; ustekinumab yielded conflicting results across small series; secukinumab failed phase 3 despite promising phase 2 data; anakinra lacked benefit in a truncated trial. In contrast, Mavrilimumab, an anti-GM-CSF-R, is showing promising results. JAK inhibitors such as upadacitinib (a JAK1 inhibitor; SELECT-GCA phase 3) are also promising, having demonstrated superior sustained remission compared with placebo, leading to regulatory approvals in 2025. These findings underscore opportunities to target upstream DC activation, macrophage polarization, and vascular remodeling pathways, potentially transforming GCA management beyond IL-6 inhibition.
Antigen-specific tolerance therapies in type 1 diabetes: Disease-specific promises meet stage-specific challenges.
Wouters A, Mathieu C, Gysemans C
Autoimmun Rev · 2026 Jun · PMID 42276316 · Publisher ↗
Type 1 diabetes (T1D) is a progressive autoimmune disease characterized by immune-mediated β-cell destruction, evolving from genetic susceptibility (stage 0) to presymptomatic autoimmunity (stages 1-2) and clinically sym...
Type 1 diabetes (T1D) is a progressive autoimmune disease characterized by immune-mediated β-cell destruction, evolving from genetic susceptibility (stage 0) to presymptomatic autoimmunity (stages 1-2) and clinically symptomatic disease (stages 3-4). Immune activation becomes increasingly pronounced throughout disease progression, highlighting a window for timely intervention to preserve residual β-cell function. Current disease-modifying therapies primarily target broad immune pathways or cell populations, such as T-cell activation and regulation. While these approaches can transiently preserve β-cell function, they lack antigen specificity, show limited durability, and may carry risks of systemic immunosuppression. Antigen-specific immunotherapy (ASI) aims to restore immune tolerance to disease-relevant antigens while maintaining overall immune competence. As pathogenic mechanisms and dominant antigenic targets evolve throughout T1D progression, ASI strategies will require stage-specific application. Moreover, genetic variation, including HLA haplotypes and insulin gene polymorphisms, shapes antigen-specific immune responses and supports patient stratification in ASI design. Early ASI approaches focused on peptide- and protein-based antigen formulations, whereas newer platforms include nucleic acid-based vaccines enabling controlled antigen expression and tolerogenic presentation. Engineered microbial delivery systems, such as Lactococcus lactis, offer targeted mucosal delivery of antigens and immunomodulators to promote localized tolerance. In parallel, adoptive cellular therapies, including regulatory T cells (Tregs) and chimeric antigen receptor (CAR) Tregs engineered to recognize β-cell antigens, represent a promising strategy to restore antigen-specific immune regulation within inflamed islets. Advanced biomaterial carriers further enhance targeted delivery and controlled antigen release. Despite its strong rationale, ASI has shown limited success in clinical trials, highlighting challenges in achieving durable immune tolerance. This may in part reflect heterogeneity in disease stage, genetic background, and underlying immune pathways, underscoring the need for biomarker-guided patient stratification. Combination approaches integrating ASI with complementary immunomodulatory strategies may therefore be required to achieve stable, antigen-specific tolerance and effectively modify disease progression.
Targeting shared immune pathways in multiple sclerosis and type 1 diabetes: Therapeutic insights from monoclonal antibodies.
Pozzilli V, Roma-Wilson MA, Pozzilli C … +1 more , Buzzetti R
Autoimmun Rev · 2026 Jun · PMID 42269843 · Publisher ↗
Multiple sclerosis (MS) and type 1 diabetes (T1D) are immune-mediated diseases that affect distinct target organs but display overlapping immunopathogenic mechanisms, including T- and B-cell dysregulation, common genetic...
Multiple sclerosis (MS) and type 1 diabetes (T1D) are immune-mediated diseases that affect distinct target organs but display overlapping immunopathogenic mechanisms, including T- and B-cell dysregulation, common genetic susceptibility, and partially convergent environmental triggers. Epidemiological data further support a bidirectional association between the two conditions, suggesting the presence of shared autoimmune pathways. These converging features provide a rationale for exploring shared therapeutic strategies based on targeted immune modulation. Monoclonal antibodies (mAbs) have emerged as powerful tools for targeted immune modulation. In MS several mAbs, particularly B-celldepleting anti-CD20 therapies, have transformed disease management. In contrast, the therapeutic impact of immunotherapy in T1D has historically been limited by rapid and largely irreversible β-cell loss, a narrow therapeutic window, and marked disease heterogeneity. The recent approval of the anti-CD3 antibody teplizumab for delaying the onset of clinical T1D represents an important milestone in this field. This review examines shared and divergent immunological mechanisms underlying MS and T1D and evaluates monoclonal antibody therapies targeting CD3, CD20, and CD40L across both diseases. By comparing their mechanisms of action and therapeutic outcomes, we highlight how differences in molecular pathogenesis, tissue context and therapeutic window influence the effect of immunetargeted therapies. We also discuss the opportunities and limitations of cross-disease immunomodulation and emerging strategies including combination and dual-indication therapies.
Corrigendum to 'Dynamic profiling in inflammatory Bowel disease: A manifesto for personalized care' [Autoimmunity Reviews 25 (2026) 104068].
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 42241804 · Publisher ↗
Abstract loading — click title to view on PubMed.
Comparison of treatment effects between ACR response criteria and target-based outcomes for contemporary rheumatoid arthritis drug approval trials: A meta-epidemiological study.
Dong W, Wang G, Hu X … +6 more , Liu X, Fang Y, Shi L, Liu X, Nie X, Guan X
Autoimmun Rev · 2026 Jun · PMID 42229607 · Publisher ↗
OBJECTIVE: Regulatory priorities diverge between agencies - the FDA maintained ACR20 response as primary endpoint in rheumatoid arthritis (RA) trials, whereas the EMA emphasized target-based outcomes. We aim to systemati...
OBJECTIVE: Regulatory priorities diverge between agencies - the FDA maintained ACR20 response as primary endpoint in rheumatoid arthritis (RA) trials, whereas the EMA emphasized target-based outcomes. We aim to systematically compare treatment effect estimates between American College of Rheumatology (ACR) response criteria (ACR20/50/70) and target-based outcomes in placebo-controlled trials of approved RA therapies. METHODS: A meta-epidemiological study was performed on randomized placebo-controlled trials investigating approved biological and targeted DMARDs (bioDMARDs and tsDMARDs) in patients with RA. Trials reporting at least one ACR response criterion and one target-based outcome were included. Odds ratios (ORs) for each outcome were computed, followed by calculation of a risk of odds ratio (ROR) to quantify differences in treatment effects between ACR and target-based outcomes. The primary outcome was the treatment effect differences between ACR20 and target-based efficacy estimates, and the second outcome was to explore which alternative ACR response criteria were concordant with target-based outcomes. RESULTS: A total of 53 RCTs (392 study arms) involving 30,778 RA patients were analyzed. Trials using ACR20 demonstrated significantly greater treatment effect estimates compared to those using remission outcomes (ROR = 0.65, 95% CI 0.52-0.81) and LDA outcomes (ROR = 0.78, 95% CI 0.69-0.89). Higher ACR thresholds (ACR50 and ACR70) showed better consistency with target-based outcomes, with ACR70 aligning with remission (ROR = 0.88, 95% CI 0.76-1.01) and ACR50 aligning with LDA (ROR = 0.95, 95% CI 0.81-1.11). Subgroup analyses indicated that the discordance between ACR20 and target-based outcomes persisted across different intervention drugs, comparison types, and previous treatments. CONCLUSION: ACR20 overestimates treatment effects relative to target-based outcomes, while ACR50/70 demonstrate better concordance. Harmonizing endpoints by integrating more stringent ACR response or co-primary endpoints (ACR response criteria + target-based outcomes) could bridge regulatory discrepancies and enhance clinical relevance in RA drug development.
Dysregulation of helper, regulatory, and follicular CD4 T cells in primary antiphospholipid syndrome: Immunopathology and implications for targeted immunomodulatory therapy.
Gaspar P, Ribeiro F, Fonseca VR … +3 more , Romão VC, Fonseca JE, Graca L
Autoimmun Rev · 2026 Jun · PMID 42229606 · Publisher ↗
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by thrombotic and/or obstetric complications in the presence of antiphospholipid antibodies (aPL). While the clinical role of aPL is well establis...
Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by thrombotic and/or obstetric complications in the presence of antiphospholipid antibodies (aPL). While the clinical role of aPL is well established, the immune mechanisms sustaining their production remain poorly understood. Recent advances implicate CD4 T cells in the immunopathogenesis of APS, with growing attention to the roles of helper (Th), regulatory (Treg), and follicular (helper, Tfh; and regulatory, Tfr) subsets in orchestrating autoreactive B cell responses within germinal centres. This review synthesizes the current evidence on CD4 T cell dysregulation in APS, with particular emphasis on primary APS, which represents a valuable clinical model for studying immune dysregulation with limited therapeutic confounding, as treatment predominantly relies on anticoagulation rather than chronic immunosuppression. Experimental studies demonstrate that autoreactive aPL-specific CD4 T cells are critical for initiating and maintaining aPL responses. In humans, APS is skewed toward Th1 and Th17 polarization, diminished Treg frequency or function, and a dysregulated Tfh/Tfr axis. Specifically, increased activated Tfh cells alongside reduced Tfr cells and skewing toward Tfh17-like subsets, have been linked to increased aPL titres and disease burden. Despite inconsistent findings across studies, likely reflecting phenotypical APS heterogeneity, distinct aPL profiles, and immunophenotyping methodological variations, the cumulative data support a model in which APS involves a coordinated disruption of CD4 T cell homeostasis, encompassing both effector and regulatory arms. By delineating these immune alterations, this review provides a framework for understanding APS immunopathology and supports CD4 T cell responses and T-B cell crosstalk as promising targets for mechanism-based immunomodulatory strategies to complement anticoagulation.
IgA vasculitis sibling clustering: From HLA-DRB1 genetic burden to nephritis risk stratification.
Ren L, Xu Y, Zhang X … +4 more , Xu J, Jiang M, Ren X, Ding Y
Autoimmun Rev · 2026 Jun · PMID 42225221 · Publisher ↗
IgA vasculitis (IgAV) is the most common systemic small-vessel vasculitis in childhood, with an annual incidence of 3 to 26.7 per 100,000 children. Although it is predominantly sporadic, its 1.9% familial clustering rate...
IgA vasculitis (IgAV) is the most common systemic small-vessel vasculitis in childhood, with an annual incidence of 3 to 26.7 per 100,000 children. Although it is predominantly sporadic, its 1.9% familial clustering rate and significant tendency for sibling comorbidity suggest a non-random pathogenesis. Multicohort GWAS data confirm that HLA-DRB1*01 and HLA-DRB1*11 are common genetic risk loci across ethnic groups. Furthermore, the core pathogenic molecule, galactose-deficient IgA1 (Gd-IgA1), exhibits a heritability of up to 64% in affected families, constituting the intrinsic basis for sibling concordance. Regarding the triggering mechanism, approximately 75% of IgAV cases are preceded by upper respiratory or gastrointestinal prodromal infections; the cross-transmission of streptococci and viruses within the family environment provides the external trigger for sibling-to-sibling transmission. Clinical phenotypes show that familial cases exhibit high consistency in the pattern of target organ involvement, and the renal involvement in the index case has significant predictive value for stratifying sibling risk. This article proposes potential mechanisms underlying the synchronized onset of disease and the formation of phenotypic mirroring among siblings, aiming to establish a clinical system for early warning and precise intervention based on family history.
CAR T cells for systemic autoimmune diseases.
Rosetti F, Madera-Salcedo IK, Cenobio LA … +2 more , Aguilar-Fuentes RE, Crispín JC
Autoimmun Rev · 2026 Jun · PMID 42225220 · Publisher ↗
Chimeric antigen receptor (CAR) T cells are an advanced cellular therapy produced by genetically modifying T cells to express a synthetic receptor that redirects them to specific cellular targets. Anti-CD19 CAR T cells,...
Chimeric antigen receptor (CAR) T cells are an advanced cellular therapy produced by genetically modifying T cells to express a synthetic receptor that redirects them to specific cellular targets. Anti-CD19 CAR T cells, approved for use in patients with B cell malignancies, have demonstrated remarkable efficacy in patients with severe refractory autoimmune diseases, such as systemic lupus erythematosus. The purpose of this review is to describe the fundamental aspects of CARs and CAR T cells and the experience of their use in systemic autoimmune diseases. In addition, we discuss the mechanisms through which they achieve clinical effectiveness and present a brief overview of where the field is headed. Even though CAR T cells are a new therapy for autoimmune diseases and their long-term effects are still unknown, they represent a promise for the clinical management of severe autoimmunity and have opened a new window for understanding the pathogenesis of systemic autoimmunity.
Combined immunosuppressive therapy in systemic sclerosis-associated interstitial lung disease: Phenotypes matter.
Marchetti M, Motta F, Tonutti A … +2 more , Selmi C, De Santis M
Autoimmun Rev · 2026 May · PMID 42214802 · Publisher ↗
Current evidence suggests that combined immunosuppressive therapy with mycophenolate mofetil (MMF)-or less frequently cyclophosphamide (CYC)- plus a biologic agent-such as rituximab (RTX) or tocilizumab (TCZ)-is a ration...
Current evidence suggests that combined immunosuppressive therapy with mycophenolate mofetil (MMF)-or less frequently cyclophosphamide (CYC)- plus a biologic agent-such as rituximab (RTX) or tocilizumab (TCZ)-is a rational and effective strategy in inflammatory, progressive systemic sclerosis (SSc)-associated interstitial lung disease (ILD), particularly when ILD coexists with other SSc domains encompassing skin involvement, arthritis, and myositis. Although recommendations agree on the importance of early treatment and close monitoring, the optimal strategy for treatment escalation in extensive or progressive SSc-ILD remains undefined. In clinical practice, switching, sequential add-on, or upfront combination therapies are therefore frequently individualized according to the disease trajectory, radiological phenotype, inflammatory activity, and patient-specific risk factors, while a universal algorithm is lacking. The path forward is therefore to embed them in phenotype-driven, treatable trait-based algorithms. While awaiting dedicated phenotype-based studies, treatment decisions should aim to reflect disease biology: in mild inflammatory and mild fibrotic SSc-ILD, MMF can be started as backbone therapy; if ILD worsening occurs or the target MMF dosage cannot be achieved, patients with the inflammatory phenotype could benefit from a sequential add-on therapy with a biologic agent, while for the fibrotic phenotype, nintedanib should be added. An upfront combination therapy is advisable for severe inflammatory and fibrotic SSc-ILD, i.e. MMF plus a biologic agent or nintedanib, respectively. In case of worsening, switching MMF with CYC should be considered. The optimal positioning of newer therapies, including emerging B-cell-targeting agents, such as ianalumab, and novel antifibrotics, such as nerandomilast, remains to be defined within this evolving therapeutic landscape.
Prevalence and clinical correlates of infection in idiopathic inflammatory myopathies: A systematic review and meta-analysis of 14,548 patients.
Yuan G, Xie X, Tang M … +3 more , Zheng X, Luo X, Xiong A
Autoimmun Rev · 2026 May · PMID 42208667 · Publisher ↗
OBJECTIVE: Infection is an important cause of mortality in patients with idiopathic inflammatory myopathies (IIMs), yet its characteristics and associated risk factors remain inadequately assessed. This study aims to ide...
OBJECTIVE: Infection is an important cause of mortality in patients with idiopathic inflammatory myopathies (IIMs), yet its characteristics and associated risk factors remain inadequately assessed. This study aims to identify and provide clear effect sizes for infection risk factors in IIMs. METHODS: In this systematic review and meta-analysis (PROSPERO CRD420251124359), we searched PubMed, Embase, and the Cochrane Library from inception to November 2025. Two reviewers independently performed study selection, data extraction, and quality assessment using the Newcastle-Ottawa Scale. Pooled prevalence and odds ratios (ORs) with 95% CIs were calculated using a random-effects model. For each clinical correlate, we prioritized the extraction of the most adjusted estimates; where unavailable, unadjusted ORs or data from 2 × 2 tables were utilized. For continuous variables, standardized mean differences (SMDs) were computed to ensure comparability across different laboratory standards. Heterogeneity was assessed using the I statistic. Subgroup analyses were conducted for anti-MDA5 positive dermatomyositis and Pneumocystis jirovecii pneumonia (PJP). RESULTS: From 10,650 identified articles, 31 studies involving 14,548 patients with IIMs were included. The pooled infection prevalence was 24% (95% CI: 18-31%). Respiratory tract was the primary infection site; PJP, aspergillosis, and herpes zoster were the most prevalent pathogens. Meta-analysis identified multiple clinical correlates of infection risk. Key patient-related factors included older age, male sex, diabetes, and hypertension. Among clinical phenotypes, anti-MDA5 positivity (OR 3.41 [2.39-4.87]), rapidly progressive interstitial lung disease (OR 1.91 [1.35-2.71]), dermatomyositis (OR 1.77 [1.17-2.69]), skin ulcerations, and dysphonia were significant markers. Laboratory indicators, synthesized as standardized mean differences (SMD), confirmed that lower lymphocyte counts (SMD -0.29 [-0.48 to -0.10]), lower albumin (SMD -0.84 [-1.16 to -0.53]) and lower hemoglobin level were robustly associated with infection. Regarding treatment-related factors, significantly increased risks were observed for higher initial glucocorticoids dose (SMD 0.51 [0.08-0.93]), methylprednisolone pulse (OR 2.15 [1.28-3.62]), cyclophosphamide (OR 2.05 [1.40-3.02]), azathioprine, and intravenous immunoglobulin. Conversely, TMP-SMX prophylaxis (OR 0.21 [0.06-0.72]), anti-TIF1 - γ positivity (OR 0.52 [0.33-0.83]) and the polymyositis phenotype (OR 0.63 [0.44-0.91]) were associated with a reduced risk of infection. CONCLUSION: Infection risk in patients with IIM is multifactorial, driven by a complex interplay of clinical phenotypes (notably anti-MDA5 positivity and RPILD), laboratory markers, and intensive immunosuppressive regimens. Our findings underscore the critical need for systematic risk stratification and support the broader implementation of targeted prophylaxis, particularly TMP/SMX, to mitigate morbidity and mortality in this vulnerable population.
Pathological reprogramming of innate immune cells drives resistance to biologics in inflammatory bowel diseases.
Diao J, Cao H, Zhou J … +1 more , Shen J
Autoimmun Rev · 2026 Jul · PMID 42190856 · Publisher ↗
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by persist ent intestinal inflammation. With a rising global incidence,...
Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated disorder characterized by persist ent intestinal inflammation. With a rising global incidence, IBD poses a significant therapeutic challenge. Although biologic agents targeting TNF, α4β7 integrin, or IL-12/ 23 p40 have improved clinical outcomes, over 40% of patients experience primary non-response or secondary loss of response within the first year, often accompanied by adverse events. This review systematically investigates the dynamic reprogramming of intestinal innate immune cells (particularly macrophages, dendritic cells, and neutr ophils,as well as emerging populations such as eosinophils and ILCs) during biologic therapy and their association with treatment resistance. Under physiological conditions, intestinal innate immune cells maintain barrier integrity, regulate immune tolerance, and facilitate tissue repair. In IBD, however, these cells undergo pathological activation characterized by pro-inflammatory polarization, dysregulated cytokine production, and disrupted interactions with the gut microbiota, thereby sustaining chronic intestinal inflammation. The efficacy of biologic agents in IBD largely relies on their capacity to restrain excessive innate immune activation and rebalance mucosal immune responses. Nevertheless, adaptive reprogramming of these innate immune cells can drive therapeutic resistance through a convergence of mechanisms: sustained activation of inflammatory signaling, metabolic reprogramming that reinforces pro-inflammatory states, induction of pathogenic T cell responses, and self-perpetuating loops that sustain tissue injury. Overall, our findings highlight reprogramming of intestinal innate immune cells as a central mechanism mediating both response and resistance to biologics, offering a mechanistic rationale for future strategies targeting immune cell-microenvironment interactions to overcome therapeutic resistance in IBD.
Racial minorities are under-represented in SLE clinical trials: A systematic review and meta-analysis.
Turk MA, Hausman J, Pope JE
Autoimmun Rev · 2026 May · PMID 42190855 · Publisher ↗
BACKGROUND: With numerous emerging treatments for systemic lupus erythematosus (SLE), it is imperative that clinical trials include diverse populations reflective of those with SLE, especially active disease. Epidemiolog...
BACKGROUND: With numerous emerging treatments for systemic lupus erythematosus (SLE), it is imperative that clinical trials include diverse populations reflective of those with SLE, especially active disease. Epidemiological data from North America and Europe indicate that the prevalence of SLE is disproportionately higher among Black populations compared to White populations, relative to their distribution in the general population. The objectives of this study were to examine the racial composition of randomized controlled trials (RCTs) in SLE from 2014 to 2024, assessing whether these trials accurately represent the diversity of SLE populations. METHODS: A systematic review of the literature was conducted using EMBASE, PUBMED, Web of Science, and Cochrane CENTRAL from Jan 1, 2014 - May 14, 2024. RCTs of pharmaceutical interventions in SLE patients were included. Studies were excluded if they had less than 50 participants, were not in English, or did not report on race/ethnicity. Revman 5.4 and SPSS were used for statistical analysis. RESULTS: Of 2505 studies identified, 63 were included. The pooled proportion of women was 91%. Among studies reporting these categories, White participants represented 61% of trial participants, Black participants 14%, Asian participants 14%, and Indigenous (including Native American) participants 8%, whereas fewer than 1% were Pacific Islanders. Hispanic/Latino ethnicity, which was variably reported across studies and may overlap with racial categories, was reported in 37% of participants. CONCLUSION: Racial and ethnic minority groups appear under-represented in recent SLE RCTs, particularly Black participants. Interpretation of Hispanic/Latino representation is limited by inconsistent reporting of race and ethnicity across trials. Greater effort is needed to ensure that SLE research trials are generalizable to patients and equitable with respect to patient diversity.
Depression in mastocytosis: A neglected dimension of a clonal mast cell disease.
Heneberg P
Autoimmun Rev · 2026 Jul · PMID 42184879 · Publisher ↗
Depression is a highly prevalent but underrecognized comorbidity in mastocytosis, a clonal mast cell disorder characterized by aberrant proliferation and activation of mast cells. Historically, depression in patients wit...
Depression is a highly prevalent but underrecognized comorbidity in mastocytosis, a clonal mast cell disorder characterized by aberrant proliferation and activation of mast cells. Historically, depression in patients with mastocytosis was considered secondary to chronic illness or diagnostic delay. Recent studies suggest a possible biological relationship between mastocytosis and affective disturbances. Here we review clinical, biochemical, and mechanistic evidence for a putative causal link between mast cell dysregulation and depressive symptomatology. The pathophysiological pathways connecting mastocytosis to mood disorders include 1) chronic histamine overproduction, which affects monoaminergic signaling; 2) inflammatory cytokines that disrupt blood-brain barrier integrity and activate neurotoxic microglial cascades; and 3) the diversion of tryptophan metabolism through indoleamine 2,3-dioxygenase (IDO1), leading to serotonin depletion and the activation of the neurotoxic kynurenine pathway. Mastocytosis patients exhibit significantly altered serotonin and tryptophan levels, with depressive symptoms correlating closely to inflammatory and metabolic markers. Despite these findings, current clinical practice does not routinely address psychiatric symptoms in mastocytosis, and no treatment guidelines or trials have evaluated targeted psychiatric interventions. Case reports suggest that antihistamines, mast cell stabilizers, and tyrosine kinase inhibitors may improve mood, but systematic evidence is lacking. The frequent underdiagnosis and dismissal of depressive symptoms in patients with mastocytosis further obscure their clinical relevance. We suggest that depression is an important and underrecognized comorbidity in mastocytosis, with immune-mediated mechanisms likely contributing to its onset and persistence in at least a subset of patients. Revised clinical and research settings are urgently needed to integrate psychiatric evaluation, identify mechanistic biomarkers, and test biologically informed interventions.
Global and regional epidemiology of psoriatic arthritis in general population: A comprehensive systematic analysis and modelling study.
Xu J, Kang Z, Du Y … +2 more , Zhang X, Dai SM
Autoimmun Rev · 2026 May · PMID 42184878 · Publisher ↗
BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, which is refractory and recurrent, affecting patients' lives and work seriously. Therefore, measuring the frequency of disease...
BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis, which is refractory and recurrent, affecting patients' lives and work seriously. Therefore, measuring the frequency of disease in general population and obtaining PsA epidemiology data is of great significance for health care policies. OBJECTIVES: To provide a comprehensive analysis and modelling of the global epidemiology of PsA in general population. METHODS: We reviewed and analyzed studies investigating PsA epidemiology over the past 34 years. A Bayesian hierarchical linear mixed model was developed to provide comprehensive epidemiologic estimates in different countries and regions. RESULTS: According to the 75 studies we systematically reviewed, the incidence of PsA in general population varies from 0.061 per 100,000 person-years in Japan to 41.300 per 100,000 person-years in Norway and the prevalence of PsA in general population varies from 0.000% in Lebanon to 0.420% in Italy. Through the Bayesian mixed linear model we developed, the global incidence is estimated to be 11.742 (0.070, 71.694) per 100,000 person-years and the global prevalence of PsA in general population is estimated to be 0.135% (0.001%, 0.732%). CONCLUSIONS: This study summarizes the global epidemiology of PsA in different countries and regions, providing useful information for specialties in areas lacking relevant data and is also of great significance for the health care policies to distribute the medical resources well.
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