Regulation of vascular endothelial permeability is crucial for maintaining hemostasis and controlling extravasation of immune cells in response to injury or infection. A transient increase in vascular permeability is a vital response to inflammation, allowing neutrophils to invade the inflamed tissue and clear the pathogen. The close interaction between neutrophils and the activated, inflamed endothelium, followed by leukocyte trafficking across the endothelial layer, can, however, also contribute to maladaptive vascular hyperpermeability. This increased permeability allows plasma proteins and fluid to escape into the surrounding tissue, leading to edema, a hallmark and frequent complication of many inflammatory disorders. Neutrophils also contribute to the resolution of inflammation by restricting further neutrophil recruitment through chemokine degradation, the formation of neutrophil extracellular traps (NETs), and by promoting their own apoptosis via the release of pro-apoptotic microparticles. Neutrophils, therefore, also contribute to the regulation of vascular permeability and to the restoration of tissue homeostasis in inflammatory conditions. This review summarizes the known mechanisms by which neutrophils regulate acute and chronic vascular permeability in autoimmune and non-autoimmune inflammatory diseases, and highlights the potential translational implications. Finally, we discuss overlapping and distinct mechanisms in neutrophil trafficking and vascular permeability.

The management of hernia in immunocompromised patients remains a distinct surgical challenge, characterized by complex risk profiles, heightened susceptibility to infectious complications, and ambiguous consensus on optimal mesh selection and perioperative protocols. As the prevalence of immunosuppression continues to rise due to increasing organ transplant rates, autoimmune diseases, oncological therapies, and advanced age, understanding the nuances of mesh repair in this population is of paramount importance. This review synthesizes current evidence on the safety, efficacy, and outcomes of hernia mesh repair in immunocompromised adults, traversing mesh materials, infection mitigation strategies, surgical techniques, recurrence and complication rates, patient-reported outcomes, cost-effectiveness, and future research imperatives. Advanced mesh materials-particularly long-acting resorbable meshes-show superior long-term durability but at elevated cost. The risk for mesh infection and recurrence is proportionate to immunosuppression burden, comorbidities, and operative field contamination. Notably, modern synthetic meshes, when coupled with stringent perioperative infection control and risk-mitigation strategies, offer durable repair with acceptable safety profiles, even in immunocompromised hosts. There is insufficient evidence to support routine use of biologic mesh, except in select contaminated fields. Patient-reported metrics are increasingly recognized as essential for outcome assessment, though standardization remains incomplete. Cost-effectiveness favors synthetics unless contamination risks predominate or patient preference dictates otherwise. Gaps include inconsistent immunocompromised patient definitions, limited long-term data, and lack of tailored guidelines. Prospective, multicenter studies integrating real-world patient-reported and economic data are needed.

Shifts in immunometabolism in autoimmune diseases.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug-induced hypersensitivity reaction often requiring prolonged corticosteroid (CS) therapy, yet tapering is difficult due to relapse. This retrospective single-center case series evaluated the efficacy and safety of selective JAK inhibitors in facilitating CS tapering in moderate-to-severe, refractory DRESS, and in ameliorating pruritis. Six patients (median age 35 years; five females) received baricitinib or abrocitinib with CS between July 2023 and June 2024. All achieved rapid clinical improvement, with generalized lesion resolution and pruritus reduction by more than three WI-NRS points. Successful initial CS tapering occurred within 7∼12 days, and four patients discontinued CS completely within 28∼62 days, two stayed with low-dose CS due to primary autoimmune disease. Serum cytokines, particularly interleukin-5, decreased markedly after JAK inhibition. No severe adverse events occurred, including in patients with pancytopenia or hepatic dysfunction. JAK inhibitors appear effective and well-tolerated in promoting CS tapering in refractory DRESS, suggesting larger controlled studies are needed.

Retraction Note: Chronic stress-mediated dysregulations in inflammatory, immune and oxidative circuitry impairs the therapeutic response of methotrexate in experimental autoimmune disease models.

In recent years, the incidence and complexity of autoimmune diseases (AIDs) have been steadily increasing, posing grim challenges to clinical management. These diseases often involve multi-organ dysfunction and impose a pronounced burden on patients' physical and mental health. Current therapeutic strategies remain suboptimal, frequently limited by poor specificity and severe systemic side effects. With the rapid advancement of nanotechnology, nanodrugs have emerged as a potential approach on account of their enhanced targeting capability, high therapeutic efficacy, and reduced toxicity. In particular, macrophage-targeted nanodrugs have gained considerable attention, given that macrophages act as a key mediator in the onset and progression of various AIDs. This review systematically summarizes the molecular basis of macrophage involvement in autoimmunity, the design strategies of nanodrugs, and their applications across different AIDs, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis (PSO), and systemic lupus erythematosus (SLE). These nanodrugs exert their therapeutic effects primarily by modulating macrophage-mediated immune responses, specifically through reprogramming macrophage phenotypes to promote anti-inflammatory and tissue-reparative functions. By precisely reprogramming macrophage function, these nanotherapeutics offer a novel approach for AID treatment.

Background/Objectives: Hydroxychloroquine (HCQ) is used to manage various autoimmune diseases, including systemic lupus erythematosus. The prolonged use of HCQ is associated with retinopathy and irreversible visual loss due to retinal toxicity. Despite adherence to dosage regimens, patients may develop functional rather than structural changes, without detectable abnormalities on routine examination using visual acuity and optical coherence tomography (OCT). The study aimed to detect early signs of retinopathy in patients with autoimmune diseases treated with HCQ. Methods: This cross-sectional study included patients (n = 36) with autoimmune diseases who were treated with HCQ. The control group (n = 35) comprised healthy volunteers matched for age and sex. All participants were screened using colour vision tests (Ishihara, Konan ColourDX high definition [HD]), and retinal thickness was evaluated using OCT. Results: Our findings suggest a significant reduction in the contrast threshold of the L and M-cone photoreceptors compared with that of the control using Konan ColourDX HD. The OCT measurements revealed no statistically significant difference in retinal thickness between patients and controls; however, the contrast sensitivity test showed a significant reduction at all spatial frequencies (p < 0.0001). Conclusions: The current study suggests that the Konan ColourDX cone contrast test HD and contrast sensitivity testing may be valuable for periodic monitoring of patients receiving HCQ, potentially enabling earlier detection of toxicity. However, longitudinal studies with larger cohorts are needed to confirm these findings and to further establish the clinical value of these functional visual tests.

This study aims to determine the potential causal relationship between type 2 diabetes (T2D) and autoimmune liver disease (AILD) using Mendelian randomization (MR) combined with clinical case analysis. Summary statistics for T2D, autoimmune hepatitis, primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) were sourced from open genome-wide association study databases. The IVW method was used as the primary analysis. Additional sensitivity analysis was also performed to validate our results. Subsequently, clinical information on patients with AILD was collected retrospectively, while multiple potentially confounding independent effects were assessed using multivariate logistic regression analysis. The results of the forward MR analysis showed that genetically predicted T2D was associated with reduced risk of PSC (IVW: odds ratio [OR] = 0.85, 95% confidence interval [CI], 0.77-0.94, P = .001). Furthermore, the results of the reverse MR analysis revealed the genetically predicted PBC (OR = 1.96, 95% CI 1.31-3.40, P = .016) had a significant correlation with the higher risk of T2D (IVW: OR = 1.02, 95% CI, 1.00-1.04, P = .025). An analysis of the clinical sample revealed that the prevalence of T2D among patients with AILD was 27.6%. Notably, multifactorial logistic regression analysis indicated that immunoglobulin G and total bilirubin levels may serve as independent factors influencing the occurrence of T2D. Genetic evidence demonstrated that T2D reduced the risk of PSC, while PBC increased the risk of T2D. Clinical data further confirmed a high prevalence of T2D in patients with autoimmune liver disease, suggesting a bidirectional relationship that warrants further validation.

NLRP12 -associated autoinflammatory disease ( NLRP12 -AID) is a rare monogenic disorder. The p.Glu619Gln (c.1855G > C) variant in NLRP12 is classified as a variant of uncertain significance (VUS), with no previously reported clinical cases. We describe a 16-year-old Chinese girl with a 9-year history of periodic high fevers (>39 °C), cold-triggered urticarial rashes, and polyarticular arthralgia. Previous misdiagnoses included recurrent infections and juvenile idiopathic arthritis. Laboratory tests showed elevated levels of interleukin-6 (IL-6) and acute-phase reactants. A lymph node biopsy confirmed necrotizing lymphadenitis. Extensive testing ruled out infections, autoimmune diseases, and cancers. Whole-exome sequencing identified a heterozygous NLRP12 p.Glu619Gln variant. Structural analysis with AlphaFold2 predicted that the mutation causes local structural destabilization and impairs function. After treatment with baricitinib (2 mg/day), the patient experienced rapid symptom relief within 2 weeks, with IL-6 levels decreasing from 17.8 pg./mL to 2.1 pg./mL and maintained clinical control over 12 months of follow-up. This is the first reported case providing multiple lines of evidence linking the NLRP12 p.Glu619Gln VUS to a typical autoinflammatory profile. Characteristic symptoms, inflammatory markers, histopathology, and a notable response to JAK inhibition support the diagnosis. Our findings suggest reclassifying this variant as likely pathogenic and propose baricitinib as a targeted therapy for NLRP12 -AID.

Background: Rheumatoid arthritis (RA) is a systemic, pro-inflammatory, autoimmune disease that mainly affects the joints in a symmetrical manner. Differential proteomic profiling through Sequential Window Acquisition of all Theoretical Fragment Ion Mass Spectra (SWATH-MS/MS) helps in a better understanding of the RA pathogenesis. In this study, we compared the differentially upregulated proteins with those associated with fibrosis to gain a deeper understanding of the fibrotic aspect of RA. Methods: We analyzed plasma proteomics data, previously obtained by SWATH-MS/MS. Our focus was on proteins associated with Leucine Rich Alpha2glycoprotein1 (LRG1) and we employed an in silico method. Results: We identified common proteins between RA and fibrosis. Among them, LRG1 and Serine Protease Inhibitor Clade A, Member 1 (SERPINA1) showed a high co-expression score in the gene clusters. LRG1 is both pro-inflammatory and pro-fibrotic, while SERPINA1 is an anti-inflammatory protein that inhibits pro-inflammatory and pro-fibrotic molecules (Elastase). Further, docking studies and a simulation study of the docked complexes with the analysis of Hydrogen bonds, Solvent Accessible Surface Area (SASA), Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and Radius of gyration (Rg), suggested a strong interaction between the two partners, LRG1 and SERPINA1. Conclusions: Our study suggests that LRG1 may inhibit SERPINA1 and promote inflammation and fibrotic processes by disrupting SERPINA1’s primary function.

The human immune system depends on microbial partners to maintain restraint. Short-chain fatty acids (SCFAs), produced by anaerobic fermenters in the gut, mouth, and skin, act as biochemical “peace signals” that calm immune activation and promote tolerance. In this hypothesis, “peace signals” refer primarily to microbially derived SCFAs; additional microbial metabolites are discussed as possible but more speculative contributors to immune restraint. This Microbial Peace-Signal Hypothesis proposes that immune homeostasis is not a static legacy of early-life microbial exposure, but a continuous partnership with these commensal fermenters. Modern lifestyle factors—including excessive hygiene, antibiotics, and low-fiber diets—have collapsed the ecological niches that support SCFA-producing guilds. Their loss silences microbial peace signals and drives the epidemic rise of allergies and autoimmune diseases. Unlike the “hygiene” or “old friends” hypotheses, this framework positions microbial peacekeeping as a lifelong metabolic function. It predicts that restoring SCFA producers across all major surfaces—gut, oral, and skin—will reduce immune overactivation systemically. This hypothesis unites clinical, ecological, and evolutionary evidence, suggesting that maintaining distributed SCFA-producing microbiomes is the foundation of long-term immune peace.

Epidermodysplasia verruciformis (EV) is a rare dermatologic disorder marked by an increased susceptibility to β-human papillomavirus infections and a heightened risk of cutaneous squamous cell carcinoma. While classically associated with autosomal recessive pathogenic variants in TMC6, TMC8, and CIB1, recent reports have expanded the disease spectrum to include acquired forms occurring in immunocompromised individuals, including those with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), organ transplants, and autoimmune disease. Both inherited and acquired EV share similar clinical and histopathologic features: flat-topped or hypopigmented papules in sun-exposed areas and characteristic "blue cells" on biopsy. Advances in molecular diagnostics, such as RNA chromogenic insitu hybridization, allow for spatial detection of transcriptionally active human papillomavirus (HPV) within skin lesions. Although treatment remains largely symptomatic, topical and systemic retinoids, immunomodulatory agents, and HPV vaccines have shown variable success. Experimental strategies such as zinc supplementation and CRISPR/Cas9 gene-editing are under investigation and offer future therapeutic potential. This review highlights the evolving understanding of both genetic and acquired forms of EV and incorporates a comprehensive review of 47 inherited EV and 67 acquired EV publications. Cases were analyzed for demographic patterns, genotype-phenotype associations, and diagnostic trends with selected statistical testing to assess significant relationships. In classic and nonclassic EV cases, patients in the classic EV group were diagnosed at a significantly older age than those in the nonclassic group. In acquired EV (AEV), HIV-associated presentations occurred at significantly younger ages, and autoimmune-related AEV occurred primarily in female patients. There was a strong association between underlying disease and sex distribution. HIV-associated AEV predominantly affects males.

To evaluate the safety and efficacy of a novel endocapsular device used during cataract surgery at the 12-month follow-up. A cohort study was conducted in a university-affiliated private practice. Adults with age-related cataracts, intraocular lens power between 14 and 26 diopters, and no other ocular pathology were included prospectively. Exclusion criteria included diabetes, previous ocular surgery, cardiac conditions, and autoimmune diseases. One eye per patient was randomly assigned to receive the device before intraocular lens implantation. Follow-ups were conducted preoperatively and at 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. The primary safety endpoint was the incidence of adverse events; the primary efficacy endpoint was the incidence of posterior capsule opacification (PCO) postoperatively at 12 months. A control group was formed retrospectively for comparison of PCO at 12 months. Spherical equivalent, corrected distance visual acuity, and intraocular pressure were also measured. A total of 121 patients were enrolled. Sixteen adverse events occurred in 12 patients; all resolved and were deemed unrelated to the device. PCO incidence at 12 months was 0.83% in the experimental group vs. 13.0% in the control group. The spherical equivalent stabilized by 3 months. At 12 months, the mean corrected distance visual acuity and intraocular pressure were 0.03 ± 0.07 logarithm of the minimum angle of resolution and 11.23 ± 2.03 mmHg, respectively. The new device seems to be safe and have a beneficial impact on PCO up to at least 12 months postoperatively. We report our experience with a novel, safe, endocapsular open capsule device that shows promise in preventing posterior capsule opacification in real-world clinical settings.

Currently, hypokalemia is managed with potassium supplements; however, there are some rare cases where it can hint towards autoimmune diseases such as systemic lupus erythematosus (SLE). The purpose of this case is to bring attention to the diagnostic difficulty of SLE in the absence of typical mucocutaneous features. The symptoms included weakness and swelling of the legs. The patient's history revealed persistent chronic hypokalemia over a 4-year period, during which she was treated with potassium supplements, yet without any primary cause being identified. A comprehensive evaluation found both hematological and renal abnormalities. Notably, despite the lack of classic dermatological signs of lupus, she scored 23 on the European League Against Rheumatism/American College of Rheumatology scoring system. She also screened positive for autoimmune disorders with a significant elevated antinuclear antibody profile including high lupus-specific autoantibodies. Subsequent bone marrow evaluation ruled out other hematological malignancies. Considering all the findings, she was diagnosed with SLE. She was treated with corticosteroid therapy, consistent with her diagnosis and forming part of the prescribed standard immunosuppressive treatment regimen. The patient demonstrated significant clinical improvement with regard to her symptoms and her potassium levels. She remained stable in further follow-up. This case illustrates the importance of very active investigation of the cause of persistent hypokalemia and a multidisciplinary collaboration. Autoimmunity should be considered in chronic electrolyte derangements, particularly in the presence of some blood or kidney problem. SLE is one of the conditions that can be diagnosed and treated early for better clinical outcome.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by cholestasis caused by intrahepatic small bile duct injury. Promoting the molecular mechanism of OTU deubiquitinase 5 (OTUD5) in the treatment of PBC requires further exploration. This study unraveled the molecular underpinnings of PBC through bio-informatics analysis and experimental verification for the development of targeted therapeutic strategies. This study screened immune-related genes and validated their expression patterns in whole blood of patients with PBC using microarray based on GEO datasets. The expression level of OTU deubiquitinase 5 (OTUD5) was validated in peripheral blood samples using RT-qPCR and immunofluorescence. Subsequently, proteomic bioinformatics analyses were conducted utilizing STRING and InBio Discover databases to predict interactions with the mitochondrial antiviral signalling protein (MAVS). Furthermore, immunochemical and immunofluorescence analyses of MAVS expression in liver tissues were conducted with a thorough analysis of immune cell infiltration specific to the disease by utilizing single-cell RNA sequencing (scRNA-seq) technology in peripheral blood mononuclear cells (PBMCs) derived from both patients with PBC and healthy controls. Compared with those of healthy controls, the liver tissues of patients with PBC presented increased NK cell activation, monocyte/mast cell numbers, and eosinophil numbers. Compared with those in 10 healthy controls, the expression of OTUD5 and MAVS was increased in 16 tissues of patients with PBC. High expression of OTUD5-MAVS in subpopulation 11 mononuclear macrophages was screened by PBMC scRNA-seq, and mononuclear cells with the subgroup 11 phenotype presented highly differentiated characteristics. The expression of OTUD5 and MAVS was inhibited in RAW264.7 cells when OTUD5 was knocked down (P < 0.05). This study focused on the overexpression of OTUD5 and its interaction with MAVS within macrophage subset 11 in patients with primary biliary cholangitis (PBC). The expression of OTUD5 and MAVS is increased in patients with PBC and is a potential target for the diagnosis and treatment of PBC.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune rheumatic disease whose epidemiology and clinical prognosis vary by race and sex. Observed disparities in SLE may be partly attributable to cognitive processes in clinical decision-making, which can influence diagnostic accuracy and clinical management. We aimed to examine variation in primary care physicians' (PCP) diagnosis and management of SLE when all content of a clinical case is identical, apart from race and sex. We distributed an online randomized factorial survey from 04/11/2024-06/10/2024 to PCPs across the US. Participants were presented with one of four possible SLE vignettes - Black female, White female, Black male, White male - for which all other clinical content was identical. Block randomization was used to randomly modify the race (Black/White) and sex (female/male) of the SLE "case". Primary outcomes were correct text-based responses for SLE diagnosis at initial case presentation and after reviewing additional lab results. Secondary outcomes were participants' review time and planned next steps (treatment, referral, tests) as a proxy for cognitive bias and certainty, respectively. We calculated descriptive statistics for all outcomes stratified by assigned randomized factor and used chi-square tests to evaluate between-group differences. 1031 PCPs (42.7% women, mean age 52.1 ± 12.1 years) completed the case. At initial presentation, 63.9% of participants correctly identified SLE as a differential diagnosis. An initial diagnosis of SLE significantly differed by the race and sex of the case (p < 0.001), with the highest proportion of correct diagnoses occurring for Black female cases (72.2%) and lowest for White male cases (55.3%). Median review time for correct initial diagnoses was longest for White male cases (175 s). After participants reviewed lab results, the overall proportion assigning a final diagnosis of SLE (63.9%) remained unchanged from the initial diagnosis. A patient's race and sex may influence diagnostic accuracy and clinical decision-making for SLE in primary care. The observed variation in diagnostic accuracy, which aligns with the descriptive epidemiology of SLE, highlights the need for targeted interventions to ensure equitable diagnostic processes.

Recent studies have highlighted the role of lipid metabolic reprogramming in the pathogenesis of vitiligo, a common autoimmune skin disease characterized by acquired depigmentation. Patients with vitiligo exhibit alterations in fatty acid metabolism, dysregulation of lipid metabolism–related proteins, and increased lipid oxidative stress. Abnormal lipid metabolism may also promote disease progression by modulating the immune microenvironment. Concurrently, immune cell dysfunction and aberrant cytokine secretion impair keratinocyte function, thereby exacerbating melanocyte destruction. This review systematically examines lipid metabolic reprogramming in vitiligo, its defining features, and its relevance to disease pathogenesis, offering a novel perspective on the underlying mechanisms. By analyzing key aspects of lipid metabolic reprogramming, this review highlights the pivotal role of lipid metabolism in vitiligo onset and progression; it provides a theoretical framework to guide future research.

Thrombotic antiphospholipid syndrome (APS) in Childhood-onset systemic lupus erythematosus (cSLE) remains a therapeutic frontier. Here, we report the first case of telitacicept (a TACI-Fc fusion protein)- induced remission in cSLE related antiphospholipid syndrome (cSLE-APS), where targeted dual BAFF(B cell-activating factor)/APRIL(a proliferation-inducing ligand) inhibition resolved life-threatening infarctions and achieved sustained disease control. During treatment, corticosteroids were successfully discontinued within six months, and a lupus low disease activity state (LLDAS) was maintained. Our findings indicate that telitacicept’s unique ability to regulate B-cell activity could target the dual pathology of cSLE-APS, offering a new therapeutic approach for this serious condition.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by clinical manifestations such as thrombocytopenia, thrombosis, and miscarriage caused by persistent positive antiphospholipid antibodies. The cardiovascular system is one of the main target systems involved, including valvular heart disease, coronary artery disease, myocardial disease, pulmonary hypertension, and intracardiac thrombus. The 2023 American College of Rheumatology(ACR)/European League Against Rheumatology(EULAR) Antiphospholipid Syndrome Classification Criteria were released, incorporating various clinical features including valvular heart lesions for quantitative assessment. Patients with APS with cardiovascular system involvement often have a poor prognosis, and there are currently no relevant guidelines or consensuses for the diagnosis and treatment of APS-related cardiovascular diseases. Therefore, it is crucial to identify the risk factors for APS-related cardiovascular diseases at an early stage and effectively predict their occurrence. This article elaborates on the risk of developing cardiovascular diseases in patients with APS.

Thyroid eye disease (TED) is an autoimmune disease involving periocular and orbital tissue. The symptoms of TED include proptosis, diplopia, visual disturbance, and lacrimal symptoms. Dry/gritty eyes, light sensitivity, and tearing are prominent lacrimal system-related symptoms. They can be misdiagnosed as dry eye syndrome, chronic conjunctivitis, or allergies. Multiple therapeutic interventions can be utilized in the management of lacrimal symptoms of TED. Lacrimal gland dysfunction occurs from immune cell infiltration of glandular tissues as well as from poor eyelid draping function causing excess exposure of the globe surface. Noninvasive treatments for lacrimal system abnormalities include local supportive measures aimed at preserving eye surface tear film, systemic and topical medications such as corticosteroids, which target inflammation, and biologicals which modify local immune responses. Surgical interventions can mitigate the negative impact of proptosis and poor eyelid draping on corneal exposure. These procedures include orbital decompression and eyelid repair. Nonmedical interventions include smoking cessation and patient education. Multidisciplinary care can reduce misdiagnoses, improve management, and reduce the negative impact on quality of life in TED. Several treatment options are currently available to mitigate lacrimal system dysfunction in TED. More targeted therapies are emerging or have recently appeared in the clinic. Patients with mild TED can benefit from supportive care aimed at symptomatic relief. An inter-disciplinary approach to managing patients with lacrimal system abnormalities can minimize the impact of lacrimal insufficiency in TED.