Autoimmunity Reviews[JOURNAL]
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200 papers
Hyaluronic acid fillers in systemic sclerosis and localized scleroderma: A systematic review.
Gkouvi A, Liapis NM, Zafiriou E … +3 more , Bogdanos DP, Katsiari CG, Simopoulou T
Autoimmun Rev · 2026 Mar · PMID 41730404 · Publisher ↗
INTRODUCTION: Patients with systemic sclerosis (SSc) or morphea increasingly inquire about cosmetic procedures, as these conditions often result in disfiguring cutaneous manifestations such as microstomia, thin lips, scl...
INTRODUCTION: Patients with systemic sclerosis (SSc) or morphea increasingly inquire about cosmetic procedures, as these conditions often result in disfiguring cutaneous manifestations such as microstomia, thin lips, sclerotic plaques or skin atrophy. Traditionally, rheumatologists prioritize immunosuppression and disease control but often fail to address aesthetic concerns. Among available interventions, hyaluronic acid (HA) fillers offer a minimally invasive approach, yet there is not enough information regarding efficacy and safety in this population. OBJECTIVE: This systematic review aims to discuss current evidence regarding the use of HA fillers in patients with SSc or morphea. METHODS: A literature search was conducted in PubMed, CENTRAL and clinicaltrials.gov from inception until January 2025. Two independent reviewers examined the studies and extracted data. Data regarding the number of patients, disease type, HA filler particulars, technique, additional treatments, immunosuppression, patient reported or other outcomes and follow-up were extracted. RESULTS: Nineteen studies met the inclusion criteria, consisting of 8 case reports, 7 case series and 4 prospective interventional studies (including one controlled study). Most common areas were the forehead, chin and perioral region. Some studies used adjuvant treatments such as Botox or Platelet-Rich Plasma (PRP). HA fillers were consistently associated with patient satisfaction and good cosmetic results. In patients with SSc, mouth opening improved and microstomia was alleviated. However, one controlled study reported no significant improvement in mouth opening compared to autologous fat grafting. Inactive morphea lesions appeared to be more responsive compared to inflammatory ones. Adverse events were mild with no reports of disease flare. CONCLUSION: HA fillers appear to be a safe and minimally invasive procedure for addressing both functional and aesthetic concerns of patients with SSc or morphea. Further randomized controlled trials are needed to clarify indications, durability and long-term safety.
Elevated lipid peroxidation biomarkers in autoimmune diseases: A systematic review and meta-analysis.
Luo Y, Hua S, Song T … +4 more , Cao M, Song S, Fang S, Zhu B
Autoimmun Rev · 2026 Mar · PMID 41707766 · Publisher ↗
BACKGROUND: Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation (LPO), is implicated in the pathogenesis of autoimmune diseases (AIDs). However, comprehensive clinical evidence establishing the...
BACKGROUND: Ferroptosis, an iron-dependent cell death pathway driven by lipid peroxidation (LPO), is implicated in the pathogenesis of autoimmune diseases (AIDs). However, comprehensive clinical evidence establishing the association between specific LPO biomarkers and AIDs is lacking. OBJECTIVE: To systematically evaluate the clinical evidence for elevated LPO in major AIDs through a meta-analysis, focusing on key biomarkers including malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α). METHODS: We searched four databases for studies reporting serum, plasma, or urinary LPO levels in patients with AIDs and healthy controls. Standardized mean differences (SMDs) were pooled using a random-effects model. RESULTS: Across 175 studies (8227 patients; 6866 controls), serum/plasma MDA levels were significantly elevated in all ten investigated AIDs: rheumatoid arthritis (RA) (SMD = 2.82), systemic sclerosis (SSc) (SMD = 2.08), Graves' disease (GD) (SMD = 1.92), Behçet's disease (BD) (SMD = 1.90), Crohn's disease (CD) (SMD = 1.71), multiple sclerosis (MS) (SMD = 1.52), psoriasis (PsO) (SMD = 1.44), ulcerative colitis (UC) (SMD = 1.32), systemic lupus erythematosus (SLE) (SMD = 1.20) and type 1 diabetes mellitus (T1DM) (SMD = 1.12). Disease-specific elevations were found for serum/plasma 8-iso-PGF2α and 4-hydroxynonenal in RA, urinary 8-iso-PGF2α in SSc and T1DM, and serum/plasma oxidized low-density lipoprotein in T1DM. MDA was higher in active or severe subgroups, with significant between-subgroup differences in GD and PsO. CONCLUSION: This meta-analysis provides robust, large-scale clinical evidence that elevated lipid peroxidation is a common feature across diverse AIDs. These findings solidify the clinical relevance of ferroptosis, positioning LPO products as promising biomarkers and underscoring the therapeutic potential of targeting ferroptosis in autoimmune conditions.
Comment on "Meta-analysis of meteorological conditions and rheumatoid arthritis".
Luo F, Yao X, Ma W
Autoimmun Rev · 2026 Mar · PMID 41687843 · Publisher ↗
This correspondence addresses critical methodological limitations in the recent meta analysis by Hu et al. regarding meteorological conditions and rheumatoid arthritis (RA). We highlight issues of clinical heterogeneity...
This correspondence addresses critical methodological limitations in the recent meta analysis by Hu et al. regarding meteorological conditions and rheumatoid arthritis (RA). We highlight issues of clinical heterogeneity arising from the conflation of disparate outcomes and inconsistent follow-up durations. Furthermore, we identify a "quality score paradox" where small-sample studies are disproportionately rated as high-quality compared to large-scale evidence. Finally, we argue that pooling data across incompatible climatic zones neglects the effect of baseline adaptation, and we suggest that the observed association between atmospheric pressure and joint swelling supports a hydraulic physical mechanism distinct from immune-mediated inflammatory flares.
A SMURF2 p.T183M variant linking four autoimmune diseases through a fibrosis-prone immune endotype.
Shi J, Pang Y, Zhang L … +4 more , Wu C, Wang Q, Li M, Zhou S
Autoimmun Rev · 2026 Mar · PMID 41687842 · Publisher ↗
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Autoimmunity in the era of immune checkpoint inhibitors: the evolving epidemiology of autoimmune diseases and the possible impact of COVID-19.
Mahroum N, Elsalti A, Alsharif M … +2 more , Jabri A, Ouban A
Autoimmun Rev · 2026 Mar · PMID 41666990 · Publisher ↗
Immune checkpoint inhibitors (ICIs) have markedly improved the prognosis of previously fatal malignancies, as evidenced by substantial gains in overall and progression-free survival in multiple clinical trials. The mecha...
Immune checkpoint inhibitors (ICIs) have markedly improved the prognosis of previously fatal malignancies, as evidenced by substantial gains in overall and progression-free survival in multiple clinical trials. The mechanism of action of ICIs is based on altering the immune response while the reported side effects display clear autoimmune features. Designated as immune-related adverse events (irAEs) affect nearly every organ system, including the gastrointestinal tract, liver, and thyroid gland, and share features with autoimmune disorders of the same organs. The severity of irAEs ranges from mild to life-threatening reactions. Many cases require systemic corticosteroids, hospitalization, and in many instances the discontinuation of ICI therapy. In this review, we present the history of ICIs, their indications, and the reported irAEs in a systematic manner. We then focus on the autoimmune nature of these side effects, with particular attention to the epidemiology of autoimmune diseases, including their female preponderance in certain age groups. In the final sections, we discuss how irAEs may be altering the epidemiology of autoimmune disease and address the possible effect of COVID-19 as a potential trigger.
Imaging the hidden player: Choroid plexus enlargement in multiple sclerosis.
Corlatescu AD, Costin HP, González-Escamilla G … +2 more , Groppa S, Fleischer V
Autoimmun Rev · 2026 Mar · PMID 41666989 · Publisher ↗
The choroid plexus (CP), one key regulator of cerebrospinal fluid (CSF) production and immune surveillance at the blood-CSF barrier, has recently emerged as a relevant structure in multiple sclerosis (MS) pathophysiology...
The choroid plexus (CP), one key regulator of cerebrospinal fluid (CSF) production and immune surveillance at the blood-CSF barrier, has recently emerged as a relevant structure in multiple sclerosis (MS) pathophysiology. This review synthesizes current evidence highlighting CP enlargement as measured with magnetic resonance imaging (MRI) as a potential biomarker of neuroinflammation and neurodegeneration in MS. We first outline the basic immunological roles of the CP, emphasizing its function as a dynamic interface facilitating immune cell trafficking and cytokine production within the CNS. Advances in MRI and PET (positron emission tomography) imaging have enabled the quantification of CP volume, revealing enlargement across different MS stages, including radiologically isolated syndrome and pediatric MS. CP volume correlates with lesion load, chronic lesion expansion, microglial activation, and inflammatory CSF profiles, suggesting its responsiveness to neuroinflammatory activity. Notably, CP enlargement is also associated with neurodegenerative processes, including gray matter atrophy, cognitive decline, and disability progression, indicating its potential role also as a surrogate marker of MS-related neurodegeneration. However, methodological variability, confounding factors and a lack of longitudinal standardization challenge the interpretation of CP metrics. We highlight the need for multimodal approaches to unravel the temporal and mechanistic significance of CP enlargement. Future research should also explore CP-targeted interventions and their relevance for MS progression. Overall, CP imaging, in particular its enlargement, offers a novel, biologically meaningful perspective into MS pathogenesis, bridging inflammatory and degenerative pathways, and holds promise for improved disease monitoring.
Regulatory mechanisms and targeted therapeutic strategies of glycolytic metabolism in rheumatoid arthritis.
Wang M, Wan K, Shu H … +7 more , Yang X, Zhou T, Xia Q, Chen Y, Wang L, Li J, Li XF
Autoimmun Rev · 2026 Mar · PMID 41666988 · Publisher ↗
Rheumatoid arthritis (RA) is a chronic autoimmune disease where glycolytic metabolism plays a crucial role in its pathogenesis. This paper delves into the characteristics, key roles, and potential therapeutic application...
Rheumatoid arthritis (RA) is a chronic autoimmune disease where glycolytic metabolism plays a crucial role in its pathogenesis. This paper delves into the characteristics, key roles, and potential therapeutic applications of glycolytic metabolism in RA. In the synovial tissues and immune cells of RA patients, glycolytic metabolism is frequently observed to be enhanced, with key enzymes such as HK2, PFK-1/PFKFB3, and PKM2 showing abnormal expression and activation. Lactate, the end product of glycolysis, is increasingly recognized as an active signaling molecule that may contribute to the maintenance of inflammation and tissue destruction through multiple proposed mechanisms. Abnormal glycolytic metabolism in immune cells (macrophages, T cells, B cells, DCs) and synoviocytes (fibroblast-like synoviocytes, osteoclasts) respectively promote inflammatory responses and joint damage. Intervention strategies targeting glycolytic metabolism, such as the use of inhibitors for HK, PKM2, LDH, and PFK-1, have been proposed. However, numerous unresolved issues remain, necessitating further basic research to clarify the regulatory mechanisms and intercellular interactions of glycolytic metabolism, as well as in-depth studies on the clinical application value of related biomarkers.
Treatment of pediatric chronic nonbacterial osteomyelitis - a systematic review.
Turner S, Roberts E, Hall N … +1 more , Hedrich CM
Autoimmun Rev · 2026 Mar · PMID 41654205 · Publisher ↗
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease most commonly affecting children and young people. CNO can cause bone pain, hyperostosis and fractures, thereby significantly impacting on pati...
Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease most commonly affecting children and young people. CNO can cause bone pain, hyperostosis and fractures, thereby significantly impacting on patients' wellbeing. The molecular pathophysiology of CNO is characterized by NLRP3 inflammasome activation and a pronounced imbalance between pro- and anti-inflammatory cytokines. In the absence of clinical trials, treatment of CNO remains empiric and is based on personal experience and published case series. This project systematically reviewed the available literature in pediatric CNO following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' (PRISMA) guidance accessing Medline, Embase, NCBI PubMed, Cochrane Library Clinical Trials, ClinicalTrials.gov, and WHO ICTRP. Nonsteroidal anti-inflammatory drugs are usually used as first-line treatment. They facilitate pain control and induce early remission in some patients but also associate with later flares. Conventional disease modifying antirheumatic drugs (DMARDs) have been used with mixed success and may be helpful in patients with associated arthritis, skin inflammation, and/or inflammatory bowel disease. Biologic DMARDs, namely TNF inhibitors, are effective for the treatment of bone and associated skin and/or bowel disease. Bisphosphonates induce rapid remission in most patients but may associate with higher relapse rates when compared to TNF inhibitors. The longstanding absence of diagnostic and, until recently, classification criteria as well as defined study endpoints, the small sample size and variable therapeutic approaches challenge interpretation of studies and comparisons between treatments. Prospective randomised controlled trials are urgently needed to improve the evidence base, resulting in approval of treatments for CNO.
Heavy and trace metals toxicity implications in the breakdown of cellular homeostasis: A risk factor for rheumatoid arthritis pathogenesis.
Ali N, Alaseem AM, Ansari MM … +5 more , Kumar S, Akhter MS, Fareed M, Alam P, Alasiri G
Autoimmun Rev · 2026 Mar · PMID 41654204 · Publisher ↗
Occupational and environmental exposure to heavy and trace metals is increasingly implicated in cellular dysfunction underlying the pathogenesis of rheumatoid arthritis (RA). While trace metals such as selenium (Se), zin...
Occupational and environmental exposure to heavy and trace metals is increasingly implicated in cellular dysfunction underlying the pathogenesis of rheumatoid arthritis (RA). While trace metals such as selenium (Se), zinc (Zn), and copper (Cu) are essential for the regulation of immune and inflammatory responses, excessive or imbalanced exposure can disrupt physiological homeostasis. In contrast, exposure to heavy metals including lead (Pb), mercury (Hg), cadmium (Cd), and nickel (Ni) poses significant risks to joint health and has been increasingly associated with progressive joint tissue deterioration. Accumulating evidence indicates that metal-induced toxicity disrupts cellular homeostasis by promoting reactive oxygen species (ROS)-mediated oxidative stress and impairing key cellular processes, including apoptosis, ferroptosis, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Moreover, heavy metals may interfere with the autophagy-lysosomal pathway, a critical mechanism for maintaining cellular integrity and immune balance. This review underscores the importance of understanding the complex interactions between heavy and trace metal exposure and their roles in cellular dysfunction and joint tissue degeneration. Elucidating the molecular mechanisms underlying metal-induced toxicity is essential for the development of targeted therapeutic strategies and effective preventive interventions aimed at mitigating RA progression.
Sarcoidosis: Disease mechanisms, diagnostic pathway and treatment.
Miedema J, Nunes H, Dalm VASH … +2 more , Judson MA, Spagnolo P
Autoimmun Rev · 2026 Mar · PMID 41651390 · Publisher ↗
Sarcoidosis is an inflammatory granulomatous disease that affects people worldwide and can involve virtually any organ but most commonly the lungs and thoracic lymph nodes. The cause of sarcoidosis remains unknown, but o...
Sarcoidosis is an inflammatory granulomatous disease that affects people worldwide and can involve virtually any organ but most commonly the lungs and thoracic lymph nodes. The cause of sarcoidosis remains unknown, but occupational and environmental exposures, genetic background, and ethnicity are likely contributors to disease development. Recent immunological studies, including single-cell RNA sequencing and spatial transcriptomics, have increased our understanding of disease pathogenesis. Diagnosing sarcoidosis is often challenging due to the lack of a diagnostic gold standard and the remarkable variability in clinical presentation. Accordingly, the diagnosis requires the presence of compatible clinical and radiological features along with histopathological evidence of noncaseating granulomas and exclusion of other granulomatous diseases. The differential diagnosis includes infection, drug-induced granulomatosis, inborn error of immunity, vasculitis and malignancies. Sarcoidosis often resolves spontaneously, but it is not a benign disease. Up to one-third of patients develops chronic or progressive disease, which carries an increased risk of organ failure or death. Treatment is not always required, but is clearly indicated for progressive pulmonary disease, symptomatic cardiac or central nervous system involvement, and significantly impaired quality of life. Treatment aims to decrease symptom burden and preserve organ function. Corticosteroids have been considered first-line treatment for decades, but their long-term use is associated with substantial toxicity. Recently, methotrexate was found to be equally effective as prednisone as first-line treatment in pulmonary sarcoidosis. The identification of novel pathways involved in disease pathogenesis has suggested JAK inhibitors and mTOR inhibitors as potential therapies. More efficacious and better tolerated therapies are urgently needed; however, the rarity of the disease, its heterogeneous clinical course and the lack of prognostic biomarkers make it difficult to design and implement clinical trials of novel therapies.
Causation-based SLE diagnostic criteria should replace advance-repressing SLE classification criteria.
Rekvig OP, Tsokos GC
Autoimmun Rev · 2026 Mar · PMID 41628786 · Publisher ↗
Systemic lupus erythematosus (SLE) presents with diverse clinical manifestations originating from multiple contributing factors employing a complex array of pathogenetic pathways. Understanding the origin of the disease...
Systemic lupus erythematosus (SLE) presents with diverse clinical manifestations originating from multiple contributing factors employing a complex array of pathogenetic pathways. Understanding the origin of the disease is stifled by the assumption that a set of classification criteria represent one disease. Efforts to continuously refine the SLE classification criteria over the last 50 years have been based on the assumption that they will solve core aspects of SLE. Yet, this optimism has failed to deliver, because it is not possible to conquer a complex disease through criteria which are arbitrarily selected, but not supported by causal mechanisms. We propose to reconsider the value of SLE classification criteria and contemplate the development of diagnostic criteria directed by causality to bolster research and treatment efforts. This communication proposes that SLE diagnostic criteria should replace SLE classification criteria, at which point SLE will be studied within the context of causality. Such an accomplishment will optimize SLE research and the care of patients with SLE.
Idiopathic pericarditis in 2025: Advances in diagnosis and therapeutic strategies.
Michaud M, Jamilloux Y, Delmas C … +4 more , Lairez O, Coulier H, Bruguière E, Pugnet G
Autoimmun Rev · 2026 Mar · PMID 41619958 · Publisher ↗
Idiopathic acute pericarditis is the most frequent form of acute pericarditis in Western countries. Although the short-term course of an uncomplicated first episode is often benign, a substantial proportion of patients p...
Idiopathic acute pericarditis is the most frequent form of acute pericarditis in Western countries. Although the short-term course of an uncomplicated first episode is often benign, a substantial proportion of patients progress to complicated forms with recurrences, incessant disease, or chronic constriction, leading to impaired quality of life and challenging management. In 2025, updated American and European guidelines for the diagnosis and management of pericarditis were issued, refining diagnostic criteria-particularly the role of C-reactive protein and multimodality imaging-and integrating targeted therapies such as interleukin-1 (IL-1) inhibitors. A structured assessment of risk factors for complications helps identify patients who require closer monitoring or hospitalization. Initial treatment combines non-steroidal anti-inflammatory drugs or aspirin and colchicine; in case of intolerance or resistance, second-line options include systemic corticosteroids or pharmacological blockade of IL-1. While the long-term prognosis of acute idiopathic pericarditis is generally good in terms of survival and low rates of constrictive pericarditis, recurrent and incessant forms are associated with significant morbidity. Individualized, risk-adapted management and prolonged follow-up are therefore recommended. This review summarizes contemporary data on the pathophysiology, diagnosis, management, and outcomes of idiopathic pericarditis, with a focus on autoinflammatory mechanisms and IL-1-targeted therapies.
Recent advances in the mechanisms and treatment of cuproptosis in autoimmune diseases.
Liu Y, Bao X, Dai X … +5 more , Liu X, Zhu D, Qiao J, Pan H, Wang J
Autoimmun Rev · 2026 Feb · PMID 41592619 · Publisher ↗
Autoimmune diseases, characterized by the immune system's erroneous attack on the body's own tissues, are highly challenging to treat. Recently discovered cuproptosis, triggered by excess copper ions, leads to the abnorm...
Autoimmune diseases, characterized by the immune system's erroneous attack on the body's own tissues, are highly challenging to treat. Recently discovered cuproptosis, triggered by excess copper ions, leads to the abnormal accumulation of acetylated proteins and mitochondrial dysfunction, and has become a research hotspot in this field. Recent studies have shown that cuproptosis-related genes (CRGs) play a potential role in various autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Primary Sjögren's syndrome (pSS), and ankylosing spondylitis (AS), and hold promise for diagnosis and regulation. This article systematically reviews the latest progress of cuproptosis in autoimmune diseases, explores the potential of CRGs as diagnostic biomarkers and immune modulators, evaluates the therapeutic potential of targeting CRGs, and looks forward to how nanotechnology can revolutionize treatment strategies. By elucidating the mechanisms of cuproptosis in autoimmune diseases, this article aims to pave new paths for future research and lay the foundation for innovative therapies.
LAG-3 in (auto)immunity and cancer - Emphasising its role in antigen presenting cells.
Wiśniewska A, Sarnowska E, Kozak K … +2 more , Rutkowski P, Sobczuk P
Autoimmun Rev · 2026 Feb · PMID 41587647 · Publisher ↗
The growing popularity of immunotherapy shows a promising future for cancer treatment. However, a significant need to develop new therapeutics that could be successfully used in therapy still remains, especially in "immu...
The growing popularity of immunotherapy shows a promising future for cancer treatment. However, a significant need to develop new therapeutics that could be successfully used in therapy still remains, especially in "immune-cold" tumors that are not responsive to classic anti-PD-1 treatment. Therefore, the discovery of lymphocyte activation gene-3 (LAG-3) as a new immune checkpoint (IC) molecule that physiologically participates in auto-tolerance mechanisms preventing auto-aggression was a significant milestone in immuno-oncology. Two main approaches aim to introduce LAG-3-directed therapies into clinical practice: anti-LAG-3 antibodies that are meant to inhibit LAG-3 function and recombinant soluble LAG-3 form that aim to activate immune response, especially by interacting with the antigen-presenting cells (APCs). So far, studies show that both approaches may be safe and effective anti-cancer treatment options. This review summarises the role of LAG-3 in immune response and emphasises the role of this IC molecule and its soluble form on APCs function, while also noting the primary physiological function of LAG-3 in autoimmunity and providing a dual perspective of the pros and cons of this novel anti-cancer therapy.
Metabolic traits of T cells and the implications in autoimmune diseases.
Zhou Y, Zhou Y, Zhu Q … +2 more , Guo W, Li C
Autoimmun Rev · 2026 Feb · PMID 41580224 · Publisher ↗
The metabolic activities of T cells play a pivotal role in regulating their activation, differentiation, and effector functions. In recent years, it has emerged as a key focus of research in the maintenance of immune hom...
The metabolic activities of T cells play a pivotal role in regulating their activation, differentiation, and effector functions. In recent years, it has emerged as a key focus of research in the maintenance of immune homeostasis and the modulation of inflammatory responses. T cells not only rely on metabolic reprogramming to meet their energy and biosynthesis demands, but also utilize intermediate metabolites to regulate epigenetic modifications and then affect gene expression and cell fate. More importantly, T cell metabolism faces adaptive pressures in tissue-specific microenvironments, which impact their effector capabilities and participate in immune tolerance maintenance. Currently, traditional immunosuppressive therapy still has limitations in the treatment of autoimmune diseases, with notable side effects. Meanwhile, targeting T cell metabolism, as an emerging strategy for intervening in autoimmune responses, has demonstrated promising potential in multiple research studies. This review provides a comprehensive overview of the metabolic characteristics of T cells at different developmental stages and functional states, explores the interactive mechanisms between metabolism and epigenetic regulation in T cells, and discusses the influence of tissue microenvironments on T cell metabolic behavior. Finally, we highlighted recent advancements in targeting T cell metabolism for treating systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis. This provides new directions for developing precise clinical intervention strategies for patients with autoimmune diseases.
Gastrointestinal histology of systemic sclerosis: A systematic review.
Strother AK, Anderton RM, Kalavar N … +8 more , Ayla AY, Ashby T, Mayer A, Dongre R, Bonomi F, Randone SB, Hughes M, McMahan ZH
Autoimmun Rev · 2026 Feb · PMID 41580223 · Publisher ↗
OBJECTIVE: To systematically review and synthesize the histological findings of gastrointestinal (GI) tissue in patients with systemic sclerosis (SSc), aiming to clarify the role of fibrosis and other pathological proces...
OBJECTIVE: To systematically review and synthesize the histological findings of gastrointestinal (GI) tissue in patients with systemic sclerosis (SSc), aiming to clarify the role of fibrosis and other pathological processes in SSc-related GI disease. METHODS: A comprehensive literature search was conducted across MEDLINE (OVID), Web of Science, and Cochrane Library databases for studies published in English from 1960 to 2025. Inclusion criteria required studies to report qualitative histological findings from GI tissue (esophagus to anorectum) in adult SSc patients, excluding those with overlapping autoimmune diseases or malignancy. Data extraction and appraisal were performed independently by multiple reviewers. RESULTS: Of 1697 screened articles, 36 met inclusion criteria. Histological analysis revealed that fibrosis, while common, was not universal nor evenly distributed across GI layers. The mucosa predominantly exhibited inflammatory infiltrates (mast cells, macrophages, lymphocytes), villous atrophy, and less frequent fibrosis. Submucosal findings were inconsistent, with variable reports of vascular changes and nerve plexus degeneration. The muscularis layer showed near-universal smooth muscle atrophy and variable fibrosis, with decreased density of interstitial cells of Cajal (ICC) in some studies. Neuronal and mitochondrial pathology were underreported. CONCLUSION: GI pathology in SSc is multifaceted, involving inflammation, cellular degeneration, neuronal dysfunction, and smooth muscle atrophy, with fibrosis as a variable feature. Standardization of histological reporting and further ultrastructural studies are needed to elucidate mechanisms and guide future research and therapeutic strategies.
Risk of infection for different B-cell targeting agents in treating systemic lupus erythematosus: A systematic review and network meta-analysis.
Yu Z, Lin Y
Autoimmun Rev · 2026 Feb · PMID 41570871 · Publisher ↗
OBJECTIVES: This study aimed to assess the risk of infections in the treatment of systemic lupus erythematosus (SLE) with various B-cell targeting agents. METHODS: We systematically searched PubMed, Web of Science, Cochr...
OBJECTIVES: This study aimed to assess the risk of infections in the treatment of systemic lupus erythematosus (SLE) with various B-cell targeting agents. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, and Embase for randomized controlled trials (RCTs) of B-cell targeting agents for SLE as of March 1, 2025. The risk of bias was assessed using Cochrane and NIH tools. The main outcomes were total and serious infections. We performed traditional (TMA) and network meta-analyses (NMA). The risk ratios (RRs) with 95% confidence intervals (CIs) or credible intervals (CrIs) were calculated. RESULTS: A total of 26 studies with 16,338 patients were included, involving 12 B-cell targeting agents. Overall, B-cell targeting therapy did not significantly increase the risk of infections. Nonetheless, obinutuzumab was associated with a greater risk of infections in patients with lupus nephritis compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.37]) and rituximab (RR [95% CrI] = 1.25 [1.04, 1.53]). It was also associated with an elevated risk of infections in the combined population compared to placebo (RR [95% CrI] = 1.18 [1.03, 1.36]), rituximab (RR [95% CrI] = 1.22 [1.04, 1.43]), and epratuzumab (RR [95% CrI] = 1.24 [1.06, 1.45]). BAFF/APRIL-targeting agents showed a higher risk of infections than anti-CD22 agents (only epratuzumab) (RR [95% CrI] = 1.16 [1.01, 1.34]). Low-dose therapy also showed a notably increased risk compared to placebo (RR [95% CrI] = 1.05 [1.00, 1.10]). No significant increase in the risk of serious infections was found. CONCLUSIONS: Specific B-cell targeting therapies may modestly increase the risk of total infections.
The regulatory roles of Beta-2 glycoprotein I (β2GPI) in thrombosis and hemostasis and abnormal disease conditions developed by autoantibodies against β2GPI.
Wang R, Tan XW, Yu C … +7 more , Li M, Wang S, Yuan B, Ma X, Liu Q, Matsuura E, Shen L
Autoimmun Rev · 2026 Feb · PMID 41483888 · Publisher ↗
Beta-2 glycoprotein I (β2GPI) as a core target antigen of antiphospholipid antibodies (aPLs), is a multifunctional plasma protein with phospholipid-binding properties. Under physiological conditions, β2GPI not only binds...
Beta-2 glycoprotein I (β2GPI) as a core target antigen of antiphospholipid antibodies (aPLs), is a multifunctional plasma protein with phospholipid-binding properties. Under physiological conditions, β2GPI not only binds to negatively charged phospholipids via its domain V but also interacts with various molecules, such as angiostatin4.5 (AS4.5) and annexin II. These interactions play key roles in maintaining the balance between procoagulant and anticoagulant processes and in promoting angiogenesis. β2GPI binds to pathophysiological ligands, such as apoptotic cells, oxidized low-density lipoprotein (oxLDL) and neutrophil extracellular traps (NETs). These complexes can trigger the production of anti-β2GPI autoantibodies in autoimmune patients, leading to antiphospholipid syndrome (APS). The resulting IgG immune complexes activate and impair endothelial cells, resulting in aberrant activation of the coagulation cascade, disruption of lipid metabolic homeostasis, and breakdown of immune tolerance. Together, these processes promote thrombotic events in APS and accelerate the progression of atherosclerotic plaques. This review paper summarizes the dynamic conformational transitions of β2GPI's functional domains that elucidates the dual regulatory role of β2GPI-mediated molecular interactions in thrombosis and atherosclerosis (AS) and reveals the mechanism by which anti-β2GPI autoantibodies mediate endothelial injury, thrombosis, and inflammatory amplification. These findings may provide a theoretical molecular basis for the development of novel diagnostic and therapeutic strategies targeting β2GPI. TAKE HOME MESSAGE.
The Trm-Treg Axis as a tissue-encoded immune checkpoint in chronic inflammation and autoimmunity.
Li L, Xia Y, Liu Y
Autoimmun Rev · 2026 Feb · PMID 41453589 · Publisher ↗
Tissue-resident memory T (Trm) cells, once heralded as gatekeepers of localized immune protection, have emerged as central players in the pathogenesis of chronic inflammation and autoimmunity at epithelial barriers. At t...
Tissue-resident memory T (Trm) cells, once heralded as gatekeepers of localized immune protection, have emerged as central players in the pathogenesis of chronic inflammation and autoimmunity at epithelial barriers. At the heart of this immunological paradox lies the dynamic interplay between Trm and regulatory T (Treg) cells-a tissue-encoded checkpoint that calibrates immune defense against the need for tolerance and repair. Disruption of this axis unleashes the latent pathogenicity of Trm cells, fueling persistent inflammation, epithelial dysfunction, and disease relapse. Here, we propose that the Trm-Treg interaction acts as a molecular rheostat that tunes immune homeostasis at barrier sites. We dissect the tissue-specific mechanisms that sustain this alliance, highlight its failure in diseases such as inflammatory bowel disease (IBD), psoriasis, and chronic obstructive pulmonary disease (COPD), and explore emerging therapeutic strategies aimed at recalibrating this immune checkpoint to restore durable epithelial tolerance.
The metabolic landscape of connective tissue diseases: Applications and discoveries in metabolomics research.
Wu Y, Deng D, Li Y … +7 more , Zhang S, Wu T, Huang D, Cheng L, Liu Y, Tan C, Luo Y
Autoimmun Rev · 2026 Feb · PMID 41371428 · Publisher ↗
Metabolomics has significantly advanced our understanding of connective tissue diseases (CTDs) in recent years by revealing the complex metabolic alterations that underlie these autoimmune disorders. This comprehensive r...
Metabolomics has significantly advanced our understanding of connective tissue diseases (CTDs) in recent years by revealing the complex metabolic alterations that underlie these autoimmune disorders. This comprehensive review synthesizes current knowledge on how metabolomics elucidates CTDs pathogenesis, enhances diagnostic precision, and guides therapeutic interventions. Central to this discussion are pivotal metabolic pathways-including those of amino acids, lipids, and carbohydrates-which exhibit distinct dysregulation patterns across different CTDs. These metabolic shifts not only reflect disease activity and severity but also offer potential biomarkers for early detection and monitoring. Advanced metabolomic technologies have facilitated the identification of novel therapeutic targets by uncovering the metabolic networks that govern immune responses and inflammation. Furthermore, metabolomics bridges the gap between host metabolism and gut microbiota, shedding light on how microbial metabolites influence immune homeostasis and disease progression. The integration of metabolomics with other omics disciplines promises a more holistic understanding of CTDs, paving the way for personalized medicine. This review highlights the transformative potential of metabolomics in CTDs research, underscoring its role in uncovering the molecular mechanisms driving these diseases and inspiring innovative management and treatment strategies.
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