Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Patient-perspective and feasibility of home finger-prick testing to complement and facilitate large-scale research in rheumatology.

BACKGROUND: During the COVID-19 pandemic, we developed a digital research platform to longitudinally investigate COVID-19-related outcomes in patients with rheumatic diseases and healthy controls. We used home finger-prick testing in order to collect serum samples remotely and increase the overall efficiency of the platform. The aim of the present study was to evaluate the success rate of the finger prick and patients' perspective towards the finger prick. METHODS: Serum samples were collected up to five times during follow-up, either via a venepuncture at the research institute or a finger prick from participants' home. Participants were asked to complete a digital evaluation questionnaire of the finger prick after their attempts. RESULTS: A total of 2135 patients and 899 controls performed at least one finger prick and were included in this study. The first finger prick was successfully done by 92% (95% CI: 90% to 93%) of patients, 94% (95% CI: 92% to 95%) of controls, 93% (95% CI: 92% to 94%) of all participants aged ≤70 years and 89% (95% CI: 86% to 92%) of all participants aged >70 years. Sex did not impact these success rates. Repeated failure occurred in 11/439 (0.8%) patients and 4/712 (0.6%) controls. Both patients and controls were less willing to perform a finger prick for individual healthcare compared with scientific research. CONCLUSION: The vast majority of participants, among which elderly and patients with rheumatic diseases, were able to successfully draw the required amount of blood for serological analyses. This shows that finger-prick testing is suitable for a high-throughput implementation to monitor patients remotely.

Ocular Myasthenia Gravis As Unilateral Ptosis and External Ophthalmoplegia: A Case Report.

Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating weakness and fatigue in ocular, bulbar, limb, or respiratory muscles. Initially, more than half of MG patients experience isolated ocular symptoms, such as ptosis, diplopia, or muscle paresis. This case report presents a unique occurrence of MG in a four-year-old female, showcasing a two-year history of sudden onset, persistent yet fluctuating unilateral ptosis accompanied by exo-deviation and adduction deficit in the right eye. No diplopia or systemic features were observed. Positive findings in tests, including the ice pack test, Cogan twitch sign, fatiguability, and neostigmine test, indicated ocular myasthenia. Electromyography revealed a decremental response, while anti-acetylcholine antibodies showed borderline results. Computed tomography of the brain ruled out central causes, and routine laboratory testing yielded normal results. Treatment with pyridostigmine and corticosteroids led to significant improvement in symptoms. This case emphasizes the diverse presentation of MG in ophthalmology, with ocular signs serving as indicators in approximately half of the cases. Early diagnosis and prompt treatment are crucial for enhancing long-term prognosis. Emergency physicians should consider MG as a potential cause for unilateral ocular symptoms after excluding central causes. Accurate diagnosis and comprehensive management of MG are complex yet essential for ensuring optimal patient health.

Causal associations between autoimmune diseases and sarcopenia-related traits: a bi-directional Mendelian randomization study.

Background: Sarcopenia is common in patients with autoimmune diseases (ADs); however, the causal associations between ADs and sarcopenia remain unclear. Therefore, this study investigated the causal associations using bi-directional Mendelian randomization analysis. Methods: Exposure-related single-nucleotide polymorphisms (SNPs) were extracted from genome-wide association studies (GWASs). GWAS statistics for common ADs [Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis (PSO), and multiple sclerosis (MS)] and sarcopenia-related traits [hand grip strength (HGS), appendicular fat-free mass (FFM), and walking pace] were obtained from public datasets. Inverse-variance weighting as the main method was used to evaluate the causal effect. Results: Genetically predicted CD had causal effects on whole-body FFM (ß = -0.005, p = 0.001), leg FFM (ßleft = -0.006, p = 1.8E-4; ßright = -0.007, p = 2.0E-4), and arm FFM (ßleft = -0.005, p = 0.005; ßright = -0.005, p = 0.001), while RA had causal effects on 8 sarcopenia-related traits, namely, HGS (ßleft = -2.06, p = 2.8E-38; ßright = -2.311, p = 2E-20), whole-body FFM (ß = -0.842, p = 4.7E-10), leg FFM (ßleft = -0.666, p = 2.6E-6; ßright = -0.073, p = 2.1E-3), arm FFM (ßleft = -0.63, p = 4.4E-6; ßright = -0.736, p = 4.4E-8), and walking pace (ß = -1.019, p = 6.2E-14). In the reverse direction, HGS (odds ratio [OR]left = 10.257, p = 3.6E-5; ORright = 16.445, p = 3.7E-7) had causal effects on CD, while HGS (ORleft = 0.994, p = 0.004; ORright = 0.993, p = 1.4E-4), leg FFM (ORleft = 1.003, p = 0.005; ORright = 1.005, p = 1.9E-4), and walking pace (OR = 0.985, p = 5.7E-5) were causally associated with RA. No evidence showed causal associations of UC, SLE, PSO, or MS with sarcopenia-related traits. Conclusion: Our study demonstrated that the genetic susceptibility to CD and RA was associated with high risk of sarcopenia, and some sarcopenia-related traits had causal effects on CD or RA.

Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.

BACKGROUND: Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. METHODS: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. RESULTS: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). CONCLUSION: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Autoimmune diseases and their genetic link to bronchiectasis: insights from a genetic correlation and Mendelian randomization study.

Background: Previous studies have demonstrated that autoimmune diseases are closely associated with bronchiectasis (BE). However, the causal effects between autoimmune diseases and BE remain elusive. Methods: All summary-level data were obtained from large-scale Genome-Wide Association Studies (GWAS). The univariate Mendelian randomization (UVMR) was utilized to investigate the genetic causal correlation (rg) of 12 autoimmune diseases and bronchiectasis, The Multivariable Mendelian Randomization (MVMR) method was used to explore the effects of the confounding factors. Further investigation was conducted to identify potential intermediate factors using mediation analysis. Finally, the linkage disequilibrium score regression (LDSC) method was used to identify genetic correlations among complex traits. A series of sensitivity analyses was performed to validate the robustness of the results. Results: The LDSC analysis revealed significant genetic correlations between BE and Crohn's disease (CD) (rg = 0.220, P = 0.037), rheumatoid arthritis (RA) (rg = 0.210, P = 0.021), and ulcerative colitis (UC) (rg = 0.247, P = 0.023). However, no genetic correlation was found with other autoimmune diseases (P > 0.05). The results of the primary IVW analysis suggested that for every SD increase in RA, there was a 10.3% increase in the incidence of BE (odds ratio [OR] = 1.103, 95% confidence interval [CI] 1.055-1.154, P = 1.75×10-5, FDR = 5.25×10-5). Furthermore, for every standard deviation (SD) increase in celiac disease (CeD), the incidence of BE reduced by 5.1% (OR = 0.949, 95% CI 0.902-0.999, P = 0.044, FDR = 0.044). We also observed suggestive evidence corresponding to a 3% increase in BE incidence with T1DM (OR = 1.033, 95% CI 1.001-1.066, P = 0.042, FDR = 0.063). Furthermore, MVMR analysis showed that RA was an independent risk factor for BE, whereas mediator MR analysis did not identify any mediating factors. The sensitivity analyses corroborated the robustness of these findings. Conclusion: LDSC analysis revealed significant genetic correlations between several autoimmune diseases and BE, and further MVMR analysis showed that RA is an independent risk factor for BE.

Inflammasome Molecular Insights in Autoimmune Diseases.

Autoimmune diseases (AIDs) emerge due to an irregular immune response towards self- and non-self-antigens. Inflammation commonly accompanies these conditions, with inflammatory factors and inflammasomes playing pivotal roles in their progression. Key concepts in molecular biology, inflammation, and molecular mimicry are crucial to understanding AID development. Exposure to foreign antigens can cause inflammation, potentially leading to AIDs through molecular mimicry triggered by cross-reactive epitopes. Molecular mimicry emerges as a key mechanism by which infectious or chemical agents trigger autoimmunity. In certain susceptible individuals, autoreactive T or B cells may be activated by a foreign antigen due to resemblances between foreign and self-peptides. Chronic inflammation, typically driven by abnormal immune responses, is strongly associated with AID pathogenesis. Inflammasomes, which are vital cytosolic multiprotein complexes assembled in response to infections and stress, are crucial to activating inflammatory processes in macrophages. Chronic inflammation, characterized by prolonged tissue injury and repair cycles, can significantly damage tissues, thereby increasing the risk of AIDs. Inhibiting inflammasomes, particularly in autoinflammatory disorders, has garnered significant interest, with pharmaceutical advancements targeting cytokines and inflammasomes showing promise in AID management.

High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia.

To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia (ITP), this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight (CyTOF). Thirty-six patients with ITP and nine healthy volunteers were enrolled in the study. As soluble immunomodulatory molecules, more sCD25 and sGalectin-9 were detected in ITP patients. On the cell surface, co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells. In contrast, co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets. Taking a platelet count of 30×109 L-1 as the cutoff value, ITP patients with high and low platelet counts showed different T cell immune profiles. Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions, respectively, and participate in the pathogenesis of ITP. In conclusion, the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP. They may offer novel targets to develop personalized immunotherapies.

The immunoregulatory effects of total glucosides of paeony in autoimmune diseases.

Total glucoside of paeonia (TGP) and its main active ingredient paeoniflorin, extracted from the Chinese herb Paeonia Lactiflora Pallas, exhibit potent immunomodulatory effects. TGP has been shown to inhibit inflammatory responses and disease progression in experimental models of multiple autoimmune diseases (AIDs), including rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, psoriasis, etc. TGP shows broad immunomodulatory effects on many immune cells such as T cells, macrophages, and dendritic cells, by regulating their activation, proliferation, differentiation, and production of effector molecules. Mechanistically, TGP modulates intracellular signaling transductions including JAK/STAT, NF-κB, MAPK, and PI3K/AKT/mTOR pathways. Moreover, TGP has been applied in the clinical treatment of various AIDs with satisfactory therapeutic outcomes and minor side effects. Thus, available studies have demonstrated that TGP and its bioactive constituents exhibit anti-inflammatory and immunomodulatory functions and may have extensive applications in the treatment of AIDs.

Programmed cell death in autoimmune diseases: ferroptosis.

Ferroptosis is an iron dependent cell death driven by lipid peroxidation. Over the past decade, increasing evidence has confirmed that ferroptosis plays an irreplaceable role in the occurrence and development of many diseases, including various cancers, neurodegenerative diseases, cardiovascular diseases and autoimmune diseases. Autoimmune disease is an inflammatory disease characterized by the breakdown of immune tolerance. Nowadays, accumulating evidence indicates that ferroptosis is closely related to the pathogenesis of autoimmune diseases. Therefore, this review briefly introduced the mechanism of ferroptosis, and focused on the related research of ferroptosis in multiple autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), ankylosing spondylitis (AS). In addition, we also presented the idea of targeting ferroptosis as a potential therapeutic target for patients with autoimmune diseases, which may provide a direction for the development of new therapeutic strategies.

[Restorative capability of traditional Chinese medicine in autoimmune diseases of nervous system: a literature review]. / Vosstanovitel'nyi potentsial traditsionnoi kitaiskoi meditsiny pri autoimmunnykh zabolevaniyakh nervnoi sistemy: obzor literatury.

Autoimmune diseases of the nervous system are characterized by the formation of pronounced neurological deficiency and often lead to disability. Complementary medicine as an adjuvant or preventive therapy of various diseases, including autoimmune ones, is increasingly attracting the attention of doctors and researchers. Traditional Chinese medicine (TCM) has a complex of treatment methods, including acupuncture, phytotherapy, nutrition, physical exercises and other methods that are often used in common with the recognized approaches of the official medical science. The article describes the TCM methods application in autoimmune diseases of nervous system, presents the practical experience of using acupuncture, phytotherapy, diet, physical exercises. It was concluded that TCM is important and frequently underestimated health care resource, especially in prevention and treatment of autoimmune diseases of nervous system.

Autoimmune diseases and myelodysplastic syndromes.

Autoimmune diseases (ADs) and myelodysplastic syndrome (MDS) may be associated in approximately 10-20% of cases. Although this association has been well recognized, it is not always easily diagnosed. The exact physiopathological mechanism involved has yet to be determined but seems to be multifactorial. The therapeutic decision is not well codified and often represents a challenge. But overall, glucocorticosteroids have generally proven to be effective at the expense of a high incidence of dependence and relapse. This review aims to summarize and analyze all aspects of this association to provide an overview for practitioners and clinicians. A scientific search in databases (PubMed, Scopus, Web of Science, Google Scholar) was conducted using a combination of key words such as autoimmune diseases, myelodysplastic syndromes, and association. Articles from 1992 to 2022 were considered and relevant data were collected and summarized to provide a coherent detailed overview of the coexistence of ADs and MDS.

Elevated levels of anti-Golgi antibodies: An early sign of seronegative rheumatoid arthritis.

Anti-Golgi antibodies are uncommon antibodies that exhibit specific, polarized cytoplasmic staining on the Hep-2 substrate. The objective of our study was to identify the clinical and laboratory features associated with anti-Golgi antibodies. We examined 4.5 years of data from a Turkish tertiary hospital in this retrospective cohort analysis. The indirect immunofluorescence staining patterns, antinuclear antibody (ANA) titres and clinical data of all patients were obtained from the hospital record system. A total of 146,055 ANAs were detected, of which 224 patients (0.15%) exhibited anti-Golgi antibody staining. In total, 39.4% of diagnosed patients had autoimmune diseases (AIDs). Of the AIDs, 26 (46.4%) were rheumatoid arthritis (RA). This is a very high rate and another remarkable point is that 17 (65.3%) of these patients had seronegative RA. High-titre results (1 ≥ 1/320) were more common in patients with AID. Anti-Ro52 was prevalent in 50% of extractable nuclear antigen (ENA)-positive patients, making it a remarkable finding. The majority of individuals with high-titre anti-Golgi antibodies had AID, particularly RA. The majority of these patients also tested negative for anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF). Finally, high-titre anti-Golgi antibodies may be an important serologic marker for seronegative RA in the Turkish population.

Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials.

INTRODUCTION: Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses of the 52-week, randomised, phase 3 TULIP-1 and TULIP-2 trials. METHODS: Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy. Whole-blood expression of 18 017 genes using genome-wide RNA sequencing (RNA-seq) (pooled TULIP; anifrolumab, n=244; placebo, n=258) and 184 plasma proteins using Olink and Simoa panels (TULIP-1; anifrolumab, n=124; placebo, n=132) were analysed. We compared treatment groups via gene set enrichment analysis using MetaBase pathway analysis, blood transcriptome modules, in silico deconvolution of RNA-seq and longitudinal linear mixed effect models for gene counts and protein levels. RESULTS: Compared with placebo, anifrolumab modulated >2000 genes by week 24, with overlapping results at week 52 and 41 proteins by week 52. IFNAR1 blockade with anifrolumab downregulated multiple type I and II IFN-induced gene modules/pathways and type III IFN-λ protein levels, and impacted apoptosis-associated and neutrophil extracellular trap-associated transcriptional pathways, innate cell activating chemokines and receptors, proinflammatory cytokines and B-cell activating cytokines. In silico deconvolution of RNA-seq data indicated an increase from baseline of mucosal-associated invariant and γδT cells and a decrease of monocytes following anifrolumab treatment. DISCUSSION: Type I IFN blockade with anifrolumab modulated multiple inflammatory pathways downstream of type I IFN signalling, including apoptotic, innate and adaptive mechanisms that play key roles in SLE immunopathogenesis.

The casual relationship between autoimmune diseases and multiple myeloma: a Mendelian randomization study.

Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048-1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.

Peripheral helper T cells in human diseases.

Peripheral helper T cells (Tph) are a specialized subset of CD4+ T cells with the ability to help B cells and induce antibody production. Although usually located in ectopic lymphoid-like structures (ELS), inside the peripheral blood, Tph cells can also be identified. The aberrant proliferation and functions of Tph cells are commonly found in the patients with disease. In this review, first we will summarize the biological characteristics of Tph cells, such as the expression of surface molecules, transcription factors and cytokines, and discuss its B cell help functions. Tph cells also have roles in a wide range of human diseases, including autoimmune diseases, infectious diseases, malignancies etc. Therefore, there is a strong interest in targeting Tph cells to improve treat strategies of human diseases.

Inefficient recruitment of DDX39B impedes pre-spliceosome assembly on FOXP3 introns.

Forkhead box P3 (FOXP3) is the master fate-determining transcription factor in regulatory T (Treg) cells and is essential for their development, function and homeostasis. Mutations in FOXP3 cause immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, and aberrant expression of FOXP3 has been implicated in other diseases such as multiple sclerosis and cancer. We previously demonstrated that pre-mRNA splicing of FOXP3 RNAs is highly sen-sitive to levels of DExD-box polypeptide 39B (DDX39B) and here we investigate the mechanism of this sensitivity. FOXP3 introns have cytidine (C)-rich/uridine (U)-poor polypyrimidine (py) tracts that are responsible for their inefficient splicing and confer sensitivity to DDX39B. We show that there is a deficiency in the assembly of commitment complexes (CCs) on FOXP3 introns, which is consistent with the lower affinity of U2AF2 for C-rich/U-poor py tracts. Our data indicate an even stronger effect on the conversion of CCs to pre-spliceosomes. We propose that this is due to an altered conformation that U2AF2 adopts when it binds to C-rich/U-poor py tracts and that this conformation has a lower affinity for DDX39B. As a consequence, CCs assembled on FOXP3 introns are defective in recruiting DDX39B and this leads to inefficient assembly of pre-spliceosome complexes.

Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

LncRNAs involvement in pathogenesis of immune-related disease via regulation of T regulatory cells, an updated review.

The pathophysiology of several illnesses, including cancer and autoimmune diseasesdepends on human regulatory T cells (Tregs), and abnormalities in these cells may function as triggers for these conditions. Cancer and autoimmune, and gynecological diseases are associated with the differentiation of the proinflammatory T cell subset TH17 and its balance with the production of Treg. Recently, long non-coding RNAs (lncRNAs) have become important regulatory molecules in a wide range of illnesses. During epigenetic regulation, they can control the expression of important genes at several levels by affecting transcription, post-transcriptional actions, translation, and protein modification. They might connect with different molecules, such as proteins, DNA and RNA, and their structural composition is intricate. Because lncRNAs regulatebiological processes, including cell division, death, and growth, they are linked to severaldiseases. A notable instance of this is the lncRNA NEAT1, which has been the subject of several investigations to ascertain its function in immune cell development. In the context of immune cell development, several additional lncRNAs have been connected to Treg cell differentiation. In this work, we summarize current findings about the diverse functions of lncRNAs in Treg cell differentiation and control of the Th17/Treg homeostasis in autoimmune disorders, cancers, as well as several gynecological diseases where Tregs are key players.