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Th9 cells, a subset of T-helper cells producing interleukin-9 (IL-9), play a vital role in the adaptive immune response and have diverse effects in different diseases. Regulated by transcription factors like PU.1 and IRF4, and cytokines such as IL-4 and TGF-β, Th9 cells drive tissue inflammation. This review focuses on their emerging role in immunopathophysiology. Th9 cells exhibit immune-mediated cancer cell destruction, showing promise in glioma and cervical cancer treatment. However, their role in breast and lung cancer is intricate, requiring a deeper understanding of pro- and anti-tumor aspects. Th9 cells, along with IL-9, foster T cell and immune cell proliferation, contributing to autoimmune disorders. They are implicated in psoriasis, atopic dermatitis, and infections. In allergic reactions and asthma, Th9 cells fuel pro-inflammatory responses. Targeting Foxo1 may regulate innate and adaptive immune responses, alleviating disease symptoms. This comprehensive review outlines Th9 cells' evolving immunopathophysiological role, emphasizing the necessity for further research to grasp their effects and potential therapeutic applications across diseases. PLAIN LANGUAGE SUMMARY: The immune system relies on CD4+ T cells, specifically Th9 cells, which produce Interleukin-9 (IL-9) to combat infections. Th9 cells have distinct functions regulated by various factors and are implicated in diseases, including cancer. Preclinical studies suggest Th9 cells could target tumors, but their role in cancer remains intricate. In lung and breast cancer, Th9 cells influence tumor growth and immune responses. Glioma research explores inducing Th9 cells to inhibit brain tumor growth. Th9 cells exhibit both positive and negative associations with colorectal cancer, lymphoma, and melanoma. Investigation into Th9 cells extends to autoimmune diseases like Graves' disease, inflammatory bowel disease, psoriasis, lupus, scleroderma, rheumatoid arthritis, and multiple sclerosis, where they may contribute to inflammation. In atopic dermatitis, elevated IL-9 levels correlate with disease severity, indicating Th9 cells' involvement in inflammation and cell activation. The complexity of Th9 cells underscores the necessity for disease-specific therapies. Understanding Th9 cells and IL-9 is pivotal for developing targeted treatments, emphasizing the nuanced role these cells play in diverse diseases and the potential for tailored therapeutic approaches. [ABSTRACT FROM AUTHOR]

Purpose of review: We evaluate available evidence for the role of inflammation in depression. We reappraise literature involving systemic inflammation, neuroinflammation and neurotransmission and their association with depression. We review the connection between depression, autoimmunity and infectious diseases. We revise anti-inflammatory treatments used in depression. Recent Findings: Peripheral inflammatory markers are present in a subset of patients with depression and can alter common neurotransmitters in this population but there is no clear causality between depression and systemic inflammation. Infectious conditions and autoimmune illnesses do not have a clear correlation with depression. Certain medications have positive evidence as adjunctive treatments in depression but studies are heterogenic, hence they are sparsely used in clinical settings. Summary: The current evidence does not fully support inflammation, infections or autoimmunity as possible etiologies of depression. The available studies have numerous confounders that obscure the findings. Anti-inflammatory agents may have potential for treatment of depression, but further research is needed to clarify their usefulness in routine clinical practice. [ABSTRACT FROM AUTHOR]

Monitoring anti-drug antibodies (ADAs) to infliximab and adalimumab is critical to treatment management in various autoimmune disorders. The growing need for proactive therapeutic monitoring further requires the detection of ADAs in the presence of measurable concentrations of infliximab or adalimumab. To provide robust analytical assays for clinical application, we evaluated two automated immunoassays developed using ImmunoCAP™ technology and based on the bridging format to measure serum ADAs to infliximab and adalimumab respectively. Without an acid-dissociation step, these research prototype assays can detect a positive control monoclonal ADA towards infliximab and adalimumab, ranging from < 25 ng/ml to 10,000 ng/mL. Both assays exhibit imprecision less than 20% at different ADA titer levels and can distinguish ADAs towards different drug targets. In method comparison using authentic patient samples, the quantitative results of the ADA assays are not directly comparable to two existing clinical immunoassays for ADAs (correlation coefficient rs = 0.673 for infliximab ADAs; rs = 0.510 for adalimumab ADAs), presumably due to the lack of commutable ADA standards and the polyclonal nature of ADAs. Nevertheless, there is qualitative agreement between the methods when evaluating putative positive and negative patient samples (overall agreement 0.83 for infliximab ADAs; 0.76 for adalimumab ADAs). Biotin and high levels of rheumatoid factors may interfere with the performance of the automated assays due to competitive binding with the biotinylated drug and non-specific formation of bridging complexes. The two ImmunoCAP assays can provide new analytical methods for proactive therapeutic monitoring of adalimumab and infliximab. [ABSTRACT FROM AUTHOR]

ABSTRACT Vitiligo is an autoimmune disorder characterized by chronic depigmentation and milk‐white patches on the skin. Skin infiltration by autoreactive CD8+ T cells causes melanocyte destruction in vitiligo. Multiple risk factors, particularly immune‐related inflammatory factors, are involved in the disappearance of melanocytes. LL37 is a classic damage‐associated molecular pattern molecule that is involved in the development of various autoimmune diseases. An enhanced expression of LL37 in vitiligo is known; however, the exact role of LL37 in melanocyte loss has not yet been elucidated. In the present study, we detected increased LL37 expression in vitiligo serum and lesions. Furthermore, we confirmed that cultured keratinocytes released LL37 after treatment with H2O2. Moreover, the LL37‐DNA complex enhanced the secretion of CXCL9, CXCL10, and CXCL16 from keratinocytes via the TLR9‐MyD88 signaling pathway and facilitated the migration of CD8+ T cells. Altogether, our study demonstrates that LL37 released from keratinocytes binds to DNA and contributes to melanocyte destruction under oxidative stress‐induced autoimmunity in vitiligo. [ABSTRACT FROM AUTHOR]

Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery–Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Sjögren’s disease (SjD) is a systemic autoimmune disorder characterized by dry eyes and mouth caused by chronic inflammation and is often accompanied by various extra-glandular manifestations, including fatigue and diffuse pain. Although the pathogenesis of the disease remains elusive, several factors (e.g. environmental, genetic and hormonal factors, abnormal metabolic status) are associated with this condition. Accumulating evidence suggests a potential role of cholesterol metabolism in immune and non-immune modulation in various diseases. In this review, we summarize the current findings on the associations between cholesterol metabolism and SjD.

Abstract Turner syndrome (TS) results from the loss of one X chromosome in phenotypic females, leading to a range of complications such as short stature, cardiovascular issues, autoimmune disorders, metabolic imbalances, osteoporosis, neurocognitive deficits, hearing loss, abnormalities in endocrine functions, infertility, disruptions in bone metabolism, and neurocognitive deficits. These diverse clinical manifestations necessitate a comprehensive and multidisciplinary approach to diagnosis and management. Growth hormone therapy stands out as a fundamental treatment for addressing the challenges associated with TS. Ongoing clinical and genomic advancements contribute to an evolving understanding of TS, shedding light on its complexities and potential therapeutic interventions. Despite progress, further research is crucial to identify candidate pathways and critical biomarkers that can alleviate the syndrome’s burden. By uncovering these insights, we aim to empower individuals with TS, enhancing their overall functioning and quality of life. In this review, we have explored the prevalent co-morbidities associated with TS, drawing insights from the current literature.

Turner syndrome (TS) results from the loss of one X chromosome in phenotypic females, leading to a range of complications such as short stature, cardiovascular issues, autoimmune disorders, metabolic imbalances, osteoporosis, neurocognitive deficits, hearing loss, abnormalities in endocrine functions, infertility, disruptions in bone metabolism, and neurocognitive deficits. These diverse clinical manifestations necessitate a comprehensive and multidisciplinary approach to diagnosis and management. Growth hormone therapy stands out as a fundamental treatment for addressing the challenges associated with TS. Ongoing clinical and genomic advancements contribute to an evolving understanding of TS, shedding light on its complexities and potential therapeutic interventions. Despite progress, further research is crucial to identify candidate pathways and critical biomarkers that can alleviate the syndrome's burden. By uncovering these insights, we aim to empower individuals with TS, enhancing their overall functioning and quality of life. In this review, we have explored the prevalent co-morbidities associated with TS, drawing insights from the current literature. [ABSTRACT FROM AUTHOR]

Objectives: To know the frequency and characteristics of neurological manifestations of probable immune origin occurring after exposure to COVID-19 vaccination. In addition, to pre-study the usefulness of the Spanish pharmacovigilance system and lymphocyte transformation test in establishing causality. Methods: Retrospective case study, including patients admitted to the Neurology department from January 2021 to May 2022 with a probable neuroimmune disorder. Demographic, clinical and COVID-19 vaccination antecedent data were collected from medical records. Results: Froma total of 108 patients, 30 were excluded due to a different etiological diagnosis after follow-up. Thirty-six patients (46.2%) had received the COVID-19 vaccine in the previous 3 months (21.8% during the previous month). BioNTech-Pfizer vaccine was the most frequent in this group (63.9%). 69/108 were female and mean age 51.2 years (SD 22.59), with no significant difference with not recentlyvaccinated (U-Mann Whitney, p = 0.256). The neurological syndromes found were (vaccinated/total): polyradiculoneuropathy (8/16), encephalitis (5/11), multiple sclerosis relapse (5/16), optic neuritis (1/4), myelitis (3/6), cranial neuropathy (6/10), aseptic meningitis (1/3) and others (7/11). Acute immunosuppressive treatment was administered in 61.1% of cases and 47.2% presented complete clinical improvement, without significant differences with non-vaccinated patients (chisquare, p = 0.570). Eleven vaccinated patients were studied in the pharmacovigilance office for possible adverse drug reaction. Causality according to the Spanish pharmacovigilance system (SPVS) algorithm was "Related" to COVID-19 vaccine (score = 4) in 11 cases with positive in vitro study (lymphocyte transformation test) to polyethylene glycol-2000 and polysorbate-80 in 4 cases. Conclusion: Neuroimmune disorders appearing after administration of COVID-19 vaccine do not seem to present important differentiating clinical and/or evolutive features. Delayed hypersensitivity to vaccine excipients could be one of the pathophysiological mechanisms, and lymphocyte transformation test is a useful tool to identify it. [ABSTRACT FROM AUTHOR]

The majority of people with autoimmune disorders, including those with rheumatoid arthritis, osteoarthritis, and tendonitis report pain, stiffness, and inflammation as major contributors to their worse quality of life in terms of overall health. Of all the available treatment options, COX inhibitors are the ones that are utilized most frequently to ease the symptoms. Various signaling cascades have been reported to be involved in the pathogenesis of rheumatoid arthritis which includes JAK/STAT, MAPK, and NF-kB signaling pathways, and several allopathic inhibitors (tofacitinib and baricitinib) have been reported to target the components of these cascades and have received approval for RA treatment. However, the prolonged use of these COX inhibitors and other allopathic drugs can pose serious health challenges due to their significant side effects. Therefore, searching for a more effective and side effect–free treatment for rheumatoid arthritis has unveiled phytochemicals as both productive and promising. Their therapeutic ability helps develop potent and safe drugs targeting immune-inflammatory diseases including RA. Various scientific databases were used for searching articles such as NCBI, SpringerLink, BioMed Central, ResearchGate, Google Scholar, Scopus, Nature, Wiley Online Library, and ScienceDirect. This review lists various phytochemicals and discusses their potential molecular targets in RA treatment, as demonstrated by various in vitro, in vivo (pre-clinical), and clinical studies. Several pre-clinical and clinical studies suggest that various phytochemicals can be an alternative promising intervention for attenuating and managing inflammation-associated pathogenesis of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: It remains unclear about the pathogenesis of intracranial aneurysms (IAs) in the setting of autoimmune disorders (ADs). However, the underlying systemic inflammatory characteristics of ADs may affect IAs through shared inflammatory pathways. Therefore, this study was conducted to explore the relationship between ADs and IAs and assess causal effects. Methods: In this study, 6 common ADs were included to explore their causal relationship with IAs. Besides, a bidirectional two-sample univariable Mendelian randomization (UVMR) analysis was performed. In addition, the primary analysis was performed by the inverse variance weighted (IVW) and Bayesian weighted Mendelian randomization (BWMR) method, and a series of sensitivity analyses were performed to assess the robustness of the results. Further, the data related to ADs and IAs were collected from open genome-wide association study studies (GWASs) and the Cerebrovascular Disease Knowledge Portal (CDKP) (including 11,084 cases and 311,458 controls), respectively. These analyses were conducted based on both the East Asian and European populations. Moreover, 6 ADs were subject to grouping according to connective tissue disease, inflammatory bowel disease, and thyroid disease. On that basis, a multivariate MR (MVMR1) analysis was further performed to explore the independent causal relationship between each AD and IAs, and an MVMR 2 analysis was conducted to investigate such potential confounders as smoking, alcohol consumption, and systolic blood pressure. Finally, these results were verified based on the data from another GWAS of IAs. Results: The UVMR analysis results demonstrated that systemic lupus erythematosus (SLE) was associated with a high risk of IAs in the East Asian population (IVW OR, 1.06; 95%CI, 1.02–1.11; p  =  0.0065, UVMR), which was supported by the results of BWMR (OR, 1.06; 95%CI, 1.02–1.11; p  =  0.0067, BWMR), MVMR1 (OR, 1.06; 95%CI, 1.01–1.10; p  =  0.015, MVMR1), MVMR2 (OR, 1.05; 95%CI, 1.00–1.11; p  =  0.049, MVMR2), and sensitivity analyses. The results in the validation group also suggested a causal relationship between SLE and IAs (IVW OR, 1.04; 95% CI, 1.00–1.09; p  =  0.046). The reverse MR analysis results did not reveal a causal relationship between IAs and ADs. Conclusion: In this MR study, SLE was validated to be a risk factor for IAs in the East Asian population. Therefore, the management of IAs in patients with SLE should be highlighted to avoid stroke events. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes (T1D) and celiac disease are the most common related autoimmune disorders. There is clinical and pathological overlap between CD and type 1 diabetes T1D, two autoimmune illnesses. Approximately 8% of people with T1D had a mean prevalence of CD. Since T1D patients may not exhibit the classic intestinal symptoms of CD, active case discovery is advised in this higher-risk population. Sensitive and particular serologies, such as tissue transglutaminase (tTG) IgA, deaminated gliadin peptide (DGP) IgA, and IgG, are used for screening. Aim: The study aimed to find the relation between celiac disease biomarkers variation in diabetic type 1. Methods: This retrospective study included all patients diagnosed with CD from January 2022 to June 2023 at King Fahad Hospital in Al-Baha City, Saudi Arabia. Results: The study included 209 participants; of them 56.5% were males, and the average age of the participants was 13.2±6.1 years. Nearly half of the particpants (52.2%) were diagnosed as they have Diabetic type 1. Most of the participants were seronegative for biomarkers of celiac disease. No statistically significant difference between demographic data and seropositivity for celiac diseases. There was a higher proportion of seropositivity among non-diabetic participants compared to those diagnosed with T1D with no significant difference. Conclusion and recommendation: The prevalence of seropositivity for CD markers was low among patients diagnosed with T1D, however, healthcare professionals must be mindful of screening these patients to prevent the potential risks associated with CD, such as microvascular complications and other related health issues. [ABSTRACT FROM AUTHOR]

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin's lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn's disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin's lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care. [ABSTRACT FROM AUTHOR]

Introductıon: This retrospective study evaluated women in whom transvaginal cervical cerclage (TCC) was performed in a previous pregnancy but delivered without cervical intervention in the most recent pregnancy. The primary aim was to underline the importance of etiology based management protocols on favorable pregnancy outcomes in patients with a history of TCC. Methods: We retrospectively evaluated 34 patients with at least one failed TCC for the treatment of cervical insufficiency (CI) but who gave birth without TCC in their most recent pregnancies. Results: All patients were evaluated preconceptionally and examined for maternal risk factors. At least one risk factor was present in all cases. The autoimmune antibody positivity rate was 41.2%. Twelve patients had Hashimoto thyroiditis, two had systemic lupus erythematosus, two had pernicious anemia, and two had anti-phospholipid antibody syndrome. 32 had homozygous or heterozygous methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms, while 11 were homozygous or heterozygous for factor 5 Leiden or prothrombin-20210A gene mutations. Conclusion: The elimination and management of risk factors for cervical ripening and dilatation are important for preventing unnecessary cervical interventions. [ABSTRACT FROM AUTHOR]

Alternative splicing is the process of producing variably spliced mRNAs by choosing distinct combinations of splice sites within a messenger RNA precursor. This splicing enables mRNA from a single gene to synthesize different proteins, which have different cellular properties and functions and yet arise from the same single gene. A family of splicing factors, Serine-arginine rich proteins, are needed to initiate the assembly and activation of the spliceosome. Serine and arginine rich splicing factor 1, part of the arginine/serine-rich splicing factor protein family, can either activate or inhibit the splicing of mRNAs, depending on the phosphorylation status of the protein and its interaction partners. Considering that serine and arginine rich splicing factor 1 is either an activator or an inhibitor, this protein has been studied widely to identify its various roles in different diseases. Research has found that serine and arginine rich splicing factor 1 is a key target for neuroprotection, showing its promising potential use in therapeutics for neurodegenerative disorders. Furthermore, serine and arginine rich splicing factor 1 might be used to regulate cancer development and autoimmune diseases. In this review, we highlight how serine and arginine rich splicing factor 1 has been studied concerning neuroprotection. In addition, we draw attention to how serine and arginine rich splicing factor 1 is being studied in cancer and immunological disorders, as well as how serine and arginine rich splicing factor 1 acts outside the central or peripheral nervous system.

Artemisinin and its derivatives are widely recognized as first-line treatments for malaria worldwide. Recent studies have demonstrated that artemisinin-based antimalarial drugs, such as artesunate, dihydroartemisinin, and artemether, not only possess excellent antimalarial properties but also exhibit antitumor, antifungal, and immunomodulatory effects. Researchers globally have synthesized artemisinin derivatives like SM735, SM905, and SM934, which offer advantages such as low toxicity, high bioavailability, and potential immunosuppressive properties. These compounds induce immunosuppression by inhibiting the activation of pathogenic T cells, suppressing B cell activation and antibody production, and enhancing the differentiation of regulatory T cells. This review summarized the mechanisms by which artemisinin and its analogs modulate excessive inflammation and immune responses in rheumatic and skeletal diseases, autoimmune inflammatory diseases, and autoimmune disorders, through pathways including TNF, Toll-like receptors, IL-6, RANKL, MAPK, PI3K/AKT/mTOR, JAK/STAT, and NRF2/GPX4. Notably, in the context of the NF-κB pathway, artemisinin not only inhibits NF-κB expression by disrupting upstream cascades and/or directly binding to NF-κB but also downregulates multiple downstream genes controlled by NF-κB, including inflammatory chemokines and their receptors. These downstream targets regulate various immune cell functions, apoptosis, proliferation, signal transduction, and antioxidant responses, ultimately intervening in systemic autoimmune diseases and autoimmune responses in organs such as the kidneys, nervous system, skin, liver, and biliary system by modulating immune dysregulation and inflammatory responses. Ongoing multicenter randomized clinical trials are investigating the effects of these compounds on rheumatic, inflammatory, and autoimmune diseases, with the aim of translating promising preclinical data into clinical applications.

Background: Aneurysms of visceral abdominal arteries represent less than 3 % of all splanchnic aneurysms. Pathology is poorly understood but recent studies have focused on the role of inflammation which it can be further enhanced by a systemic inflammatory disease. Materials and Methods: A systematic literature review was conducted to highlight the unsolved aspects of this pathology and a total of 43 patients were retrieved to whom we added 1 patient treated at our Institution. Results: Mean age at presentation was 54 years with a peak of incidence between the 6th and the 7th decades of life. No racial, sex, and age differences were observed among the two groups (P=NS). In 10 (23 %) patients an inflammatory disease was associated. However, the risk of rupture was similar between patients affected with an inflammatory disease and those with a sporadic presentation (P=NS). Color ultrasound was seldomly used but its role is questionable especially in an emergency setting because of the well-known limitations. On the other hand, computed tomography angiogram always permitted diagnosis. Surgery is the treatment of choice to prevent emergent surgery. If feasible, an endovascular approach should be used either in elective or emergent setting. However, hemodynamically unstable patients should be promptly operated on with an open approach. There were 4 (9 %) deaths 1 before surgery, 3 during operation. Conclusions: Although in our revision we were unable to demonstrate that patients affected with an autoimmune diseases or chronic inflammatory conditions might have a higher risk of visceral aneurysm rupture, we recommend a proactive screening approach based on regular monitor of these patients for the presence of visceral aneurysms.

Background: Brentuximab Vedotin (BV) has revolutionized the treatment landscape for Hodgkin’s lymphoma, yet its effects on pre-existing autoimmune disorders remain elusive. Methods: Here, we present four cases of patients with concurrent autoimmune conditions—Crohn’s disease, vitiligo, type I diabetes, and minimal change disease—undergoing BV therapy for Hodgkin’s lymphoma. The patients were treated with A-AVD instead of ABVD due to advanced-stage disease with high IPI scores. Results: Our findings reveal the surprising and complex interplay between BV exposure and autoimmune manifestations, highlighting the need for multidisciplinary collaboration in patient management. Notably, the exacerbation of autoimmune symptoms was observed in the first three cases where T-cell-mediated autoimmunity predominated. Additionally, BV exposure precipitated autoimmune thrombocytopenia in the vitiligo patient, underscoring the profound disruptions in immune regulation. Conversely, in the minimal change disease case, a disease characterized by a blend of B- and T-cell-mediated immunity, the outcome was favorable. Conclusions: This paper underscores the critical importance of vigilance toward autoimmune flare-ups induced by BV in patients with concurrent autoimmune conditions, offering insights for tailored patient care.

Abstract Numerous studies establish a significant correlation between autoimmune disorders (AIDs) and prostate cancer (PCa). Our Mendelian randomization (MR) analysis investigates the potential connection between rheumatoid arthritis (RA) and PCa, aiming to confirm causal links between systemic lupus erythematosus (SLE), hyperthyroidism, and PCa. Summary statistics from genome-wide association studies provided data on PCa and three AIDs. MR analysis, using IVW as the main approach, assessed causal relationships, validated by sensitivity analysis. IVW revealed a correlation between genetically anticipated RA and PCa, notably in Europeans (OR = 1.03; 95% CI 1.01–1.04, p = 2*10−5). Evidence supported a lower PCa risk in individuals with SLE (OR = 0.94; 95% CI 0.91–0.97, p = 2*10−4) and hyperthyroidism (OR = 0.02; 95% CI 0.001–0.2, p = 2*10−3). Weighted mode and median confirmed these findings. No pleiotropic effects were observed, and MR heterogeneity tests indicated dataset homogeneity. Our study establishes a causal link between RA, SLE, hyperthyroidism, and PCa.

BackgroundCorticosteroids are anti-inflammatory medications that are used to reduce inflammation and inhibit the immune system in a variety of disorders, including allergies, asthma, systemic lupus erythematous, eczema, inflammatory bowel disease, and swollen joints or muscles. The goal of this study was to assess the level of awareness and sources of information about the side effects of corticosteroids among the general population in Saudi Arabia. MethodsThis observational cross-sectional study was conducted in Saudi Arabia using an electronic questionnaire. A non-probability convenience sampling technique was used. Statistical Package for the Social Sciences (SPSS) was used for data analysis. ResultsThe study included 755 participants from Saudi Arabia (67.3% females and 32.7% males). Around 26.8% reported using corticosteroids, and 73.9% were aware of the side effects of glucocorticoids. Among steroid users (202 participants), the most common conditions were allergies (36.1%), asthma or chronic obstructive pulmonary disease (COPD) (21.8%), and skin diseases (27.7%). The majority of respondents (57.9%) used steroids for less than 2 weeks, and topical application (52.5%) was the most common form. Only 30.7% received information about side effects at the time of prescription. The most reported side effects were truncal obesity, moon face, skin thinning, bruising, and slower wound healing. ConclusionThis study highlights the importance of promoting awareness and knowledge regarding the side effects of corticosteroids in Saudi Arabia. While overall awareness levels were relatively satisfactory, specific side effects require further attention in educational efforts.

Autoimmune disorders (AD) represent a heterogeneous group of multifactorial chronic conditions, which are triggered secondary to the loss of self-antigen tolerance. Their etiology involves genetic, epigenetic, and environmental factors; however, AD cannot be explained by these factors alone. Recent studies have shown increasing stress levels in industrialized countries and also increasing trends in the prevalence of autoimmune diseases. The oral mucosa is extremely responsive to emotional influences such as stress, anxiety and depression. Therefore, oral diseases can appear as a direct expression of emotions or indirectly, due to various psychological mechanisms. The aim of this study is to find and present possible correlations in order to support the hypothesis that psychogenic factors can play a significant role in the etiopathogenesis of autoimmune disorders in the oral cavity. The review is focused on clarifying epidemiology, etiology, pathogenesis, course, clinical signs, and management of oral lichen planus, recurrent aphthous stomatitis, psoriasis, muco-membranous pemphigoid, pemphigus, and erythema multiforme. Existing literature suggests bidirectional links between psychogenic factors and autoimmune diseases, which influence patients' psychological well-being and quality of life. Consequently, research and medical practice must continue investigations related to the proper diagnosis and clinical management of these conditions. The first signs of several diseases first appear in the oral cavity, which means that dentists can play an important role in the early diagnosis and treatment of AD oral. Although the role of psychological factors in the etiopathogenesis of AD is still underestimated, a holistic multidisciplinary approach should be implemented to provide for these health problems an appropriate diagnostic and therapeutic procedures.

Abstract Background There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations.

Children and adolescents with chronic cutaneous conditions are at risk of experiencing adverse psychosocial effects such as anxiety, depression, and loneliness. The well-being of these children's families may also be impacted by their child's condition. It is important for the quality of life of patients and their families to better understand the psychosocial impact caused by pediatric dermatologic conditions and interventions that help mitigate these effects. This review summarizes the psychological impact of the common pediatric dermatological disorders, vitiligo, psoriasis, and alopecia areata, on children and their caregivers. Studies examining quality of life, psychiatric conditions, and other measures of psychosocial impact in children and caregivers, as well as those evaluating the effectiveness of interventions aimed at addressing psychosocial effects, were included. This review highlights the increased risk that children with these conditions have in experiencing adverse psychosocial effects including quality of life impairment, psychological pathology, and social stigmatization. In addition, the specific risk factors within this population that are associated with increased negative effect such as age and severity of disease are discussed. This review demonstrates a need for increased support of these patients and their families and additional research on the effectiveness of current interventions.

Key Clinical Message: Non‐lupus full house nephropathy is a rare entity that is still poorly understood. It can complicate post‐transplant kidneys and result in a de novo process. Treatment is difficult but can be possibly achieved with optimization of immune suppression. Non‐lupus full house nephropathy is a rare entity with an unclear incidence. It describes the kidney biopsy findings of positive deposits for IgG, IgA, IgM, C3, and C1q on immunofluorescence in the absence of the classical diagnostic features of systemic lupus nephritis. This disease entity is becoming more recognized but further studies are still needed to evaluate the incidence, etiologies, and management of this condition. Transplant glomerulopathy is a major cause for renal graft loss. It can present with a wide variety of manifestations; it can cause AKI, CKD, or glomerular inflammations through an immune complex or autoimmune‐mediated damage. [ABSTRACT FROM AUTHOR]

The relentless pursuit of precision medicine has catalyzed the development of molecular and cellular tethered drug delivery systems, a burgeoning field that stands to redefine the paradigms of therapeutic delivery. This review encapsulates the cutting-edge advancements within this domain, emphasizing the engineering of molecular tethers and cellular vectors designed to ferry therapeutics directly to their target sites with unparalleled specificity and efficiency. By exploiting the unique biochemical signatures of disease states, these systems promise a substantial reduction in off-target effects and an enhancement in drug bioavailability, thereby mitigating the systemic side effects that are often associated with conventional drug therapies. Through a synthesis of recent research findings, this review highlights the innovative approaches being explored in the design and application of these tethered systems, ranging from nanotechnology-based solutions to genetically engineered cellular carriers. The potential of these systems to provide targeted therapy for a wide array of diseases, including cancer, autoimmune disorders, and neurological conditions, is thoroughly examined. This abstract aims to provide a succinct overview of the current state and future prospects of molecular and cellular tethered drug delivery systems in advancing the frontiers of precision medicine. [ABSTRACT FROM AUTHOR]

Some 90 autoimmune disorders have been described in medical literature, affecting most of the tissues within the body. Autoimmune disorders may be difficult to treat, and there is a need to develop novel therapeutic strategies for these disorders. Autoimmune disorders are characterised by mitochondrial dysfunction, oxidative stress, and inflammation; there is therefore a rationale for a role for coenzyme Q10 in the management of these disorders, on the basis of its key role in normal mitochondrial function, as an antioxidant, and as an anti-inflammatory agent. In this article, we have therefore reviewed the potential role of CoQ10, in terms of both deficiency and/or supplementation, in a range of autoimmune disorders. [ABSTRACT FROM AUTHOR]

Background: Corticosteroids are anti-inflammatory medications that are used to reduce inflammation and inhibit the immune system in a variety of disorders, including allergies, asthma, systemic lupus erythematous, eczema, inflammatory bowel disease, and swollen joints or muscles. The goal of this study was to assess the level of awareness and sources of information about the side effects of corticosteroids among the general population in Saudi Arabia. Methods: This observational cross-sectional study was conducted in Saudi Arabia using an electronic questionnaire. A non-probability convenience sampling technique was used. Statistical Package for the Social Sciences (SPSS) was used for data analysis. Results: The study included 755 participants from Saudi Arabia (67.3% females and 32.7% males). Around 26.8% reported using corticosteroids, and 73.9% were aware of the side effects of glucocorticoids. Among steroid users (202 participants), the most common conditions were allergies (36.1%), asthma or chronic obstructive pulmonary disease (COPD) (21.8%), and skin diseases (27.7%). The majority of respondents (57.9%) used steroids for less than 2 weeks, and topical application (52.5%) was the most common form. Only 30.7% received information about side effects at the time of prescription. The most reported side effects were truncal obesity, moon face, skin thinning, bruising, and slower wound healing. Conclusion: This study highlights the importance of promoting awareness and knowledge regarding the side effects of corticosteroids in Saudi Arabia. While overall awareness levels were relatively satisfactory, specific side effects require further attention in educational efforts. [ABSTRACT FROM AUTHOR]

The emergence of multi-drug-resistant autoimmune diseases poses a significant risk to human health and has garnered global attention. In this study, metformin and sulfasalazine have been used as starting materials or control. This research has successfully designed a hundred compounds, to assess their efficacy against two autoimmune disease pathogens: type 1 diabetes and rheumatoid arthritis. The DFT method was engaged to calculate the vibrational frequencies and Frontier Molecular orbitals (FMOs) of the selected compounds. The reactivity and selectivity of the selected compounds are analyzed using parameters like MEP and global reactivity descriptors, which are calculated and interpreted. The Density of state (DOS) of the molecule has been plotted and interpreted. Furthermore, docking results showed favorable interactions of the designed compound D385 with catalytically important amino acid residues. The interactions of the best active D385 when compared with the template and the standard drugs show similar binding sites. DFT studies further confirm the presence of HOMO orbital centered on the isoxazole ring further highlighting its importance for receptor-ligand hydrogen and hydrophobic interactions. The molecular dynamics simulations and MM/GBSA analysis reveal that the inhibitory nature of the designed compound D385 is a proven inhibitor of diabetes type 1 and rheumatoid arthritis inhibitor activities. Our study suggested that the designed compounds showed comparable results to that of metformin and sulfasalazine and may be used for further experimental studies. It can also be used as a pipeline to search for and design new potential autoimmune disease inhibitors. The most promising candidates from computational trials can be examined in a wet laboratory experiment before moving on to clinical trials. [ABSTRACT FROM AUTHOR]

Background: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.1), type 2 EBNA2 shares only ~ 50% amino acid identity with type 1 and thus may have distinct binding partners, human genome binding locations, and functions. Results: In this study, we examined genome-wide EBNA2 binding in EBV-1 and EBV-2 transformed human B cells to identify shared and unique EBNA2 interactions with the human genome, revealing thousands of type-specific EBNA2 ChIP-seq peaks. Computational predictions based on hTF motifs and subsequent ChIP-seq experiments revealed that both type 1 and 2 EBNA2 co-occupy the genome with SPI1 and AP-1 (BATF and JUNB) hTFs. However, type 1 EBNA2 showed preferential co-occupancy with EBF1, and type 2 EBNA2 preferred RBPJ. These differences in hTF co-occupancy revealed possible mechanisms underlying type-specific gene expression of known EBNA2 human target genes: MYC (shared), CXCR7 (type 1 specific), and CD21 (type 2 specific). Both type 1 and 2 EBNA2 binding events were enriched at systemic lupus erythematosus (SLE) and multiple sclerosis (MS) risk loci, while primary biliary cholangitis (PBC) risk loci were specifically enriched for type 2 peaks. Conclusions: This study reveals extensive type-specific EBNA2 interactions with the human genome, possible differences in EBNA2 interaction partners, and a possible new role for type 2 EBNA2 in autoimmune disorders. Our results highlight the importance of considering EBV type in the control of human gene expression and disease-related investigations. [ABSTRACT FROM AUTHOR]

Purpose: Owing to adverse event following immunization (AEFI) related to autoimmune disorders and coronavirus disease 2019 (COVID-19) vaccines sharing common biological mechanisms, identifying the risk of AEFIs associated with COVID-19 vaccines remains a critical unmet need. We aimed to assess the potential safety signals for 16 AEFIs and explore co-reported adverse events (AEs) and drugs using the global database of the World Health Organization, VigiBase. Methods: We assessed the occurrence of 16 AEFIs following COVID-19 vaccination through the Standardized MedDRA Queries group "Immune-mediated/Autoimmune Disorders" from MedDRA and performed a disproportionality analysis using reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CIs). Results: We identified 25,219 events associated with COVID-19 vaccines in VigiBase. Although rare, we detected four potential safety signals related to autoimmune disorders following COVID-19 vaccination, including ankylosing spondylitis or psoriatic arthritis (ROR 1.86; 95% CI 1.53–2.27), inflammatory bowel disease (ROR 1.77; 95% CI 1.60–1.96), polymyalgia rheumatica (ROR 1.42; 95% CI 1.30–1.55), and thyroiditis (ROR 1.40; 95% CI 1.30–1.50), with positive IC025 values. The top co-reported AEs were musculoskeletal disorders, and immunosuppressants were the most representative co-reported drugs. Conclusion: In addressing the imperative to comprehend AEFI related to autoimmune disorders following COVID-19 vaccination, our study identified four potential safety signals. Thus, our research underscores the importance of proactive safety monitoring for the identification of the four AEFIs following COVID-19 vaccination, considering the associated advantages. [ABSTRACT FROM AUTHOR]

The interplay between the immune system and the metabolic state of a cell is intricate. In all phases of an immune response, the corresponding metabolic changes shall occur to support its modulation, in addition to the signalling through the cytokine environment and immune receptor stimulation. While autoimmune disorders may develop because of a metabolic imbalance that modulates switching between T‐cell phenotypes, the effects that the interaction between T and B cells have on one another's cellular metabolism are yet to be understood in disease context. Here, we propose a perspective which highlights the potential of targeting metabolism to modulate T‐ and B‐cell subtypes populations as well as T–B and B–T cell interactions to successfully treat autoimmune disorders. Specifically, we envision how metabolic changes can tip the balance of immune cells interactions, through definite mechanisms in both health and disease, to explain phenotype switches of B and T cells. Within this scenario, we highlight targeting metabolism that link inflammation, immunometabolism, epigenetics and ageing, is critical to understand inflammatory disorders. The combination of treatments targeting immune cells that cause (T/B) cell phenotype imbalances, and the metabolic pathways involved, may increase the effectiveness of treatment of autoimmune disorders, and/or ameliorate their symptoms to improve patients' quality of life. [ABSTRACT FROM AUTHOR]

Large granular lymphocytic (LGL) leukemia is a rare lymphoproliferative disorder characterized by an expansion of clonal T or NK lymphocytes. Neutropenia-related infections represent the main clinical manifestation. Even if the disease follows an indolent course, most patients will ultimately need treatment in their lifetime. Interestingly, LGL leukemia is characterized by a high frequency of autoimmune disorders with rheumatoid arthritis being the most frequent. This review covers the pathophysiology, clinic-biological features and the advances made in the treatment of LGL leukemia. A special focus will be made on the similarities in the pathophysiology of LGL leukemia and the frequently associated rheumatic disorders. Recent advances in the phenotypic and molecular characterization of LGL clones have uncovered the key role of JAK-STAT signaling in the pathophysiology linking leukemic cells expansion and autoimmunity. The description of the molecular landscape of T- and NK-LGL leukemia and the improved understanding of the associated rheumatic disorders open the way to the development of new targeted therapies effective on both conditions. [ABSTRACT FROM AUTHOR]

Objectives: To know the frequency and characteristics of neurological manifestations of probable immune origin occurring after exposure to COVID-19 vaccination. In addition, to pre-study the usefulness of the Spanish pharmacovigilance system and lymphocyte transformation test in establishing causality.Methods: Retrospective case study, including patients admitted to the Neurology department from January 2021 to May 2022 with a probable neuroimmune disorder. Demographic, clinical and COVID-19 vaccination antecedent data were collected from medical records.Results: From a total of 108 patients, 30 were excluded due to a different etiological diagnosis after follow-up. Thirty-six patients (46.2%) had received the COVID-19 vaccine in the previous 3 months (21.8% during the previous month). BioNTech-Pfizer vaccine was the most frequent in this group (63.9%). 69/108 were female and mean age 51.2 years (SD 22.59), with no significant difference with not recently-vaccinated (U-Mann Whitney, p = 0.256). The neurological syndromes found were (vaccinated/total): polyradiculoneuropathy (8/16), encephalitis (5/11), multiple sclerosis relapse (5/16), optic neuritis (1/4), myelitis (3/6), cranial neuropathy (6/10), aseptic meningitis (1/3) and others (7/11). Acute immunosuppressive treatment was administered in 61.1% of cases and 47.2% presented complete clinical improvement, without significant differences with non-vaccinated patients (chi-square, p = 0.570). Eleven vaccinated patients were studied in the pharmacovigilance office for possible adverse drug reaction. Causality according to the Spanish pharmacovigilance system (SPVS) algorithm was “Related” to COVID-19 vaccine (score ≥ 4) in 11 cases with positive in vitro study (lymphocyte transformation test) to polyethylene glycol-2000 and polysorbate-80 in 4 cases.Conclusion: Neuroimmune disorders appearing after administration of COVID-19 vaccine do not seem to present important differentiating clinical and/or evolutive features. Delayed hypersensitivity to vaccine excipients could be one of the pathophysiological mechanisms, and lymphocyte transformation test is a useful tool to identify it.

Cardiovascular disease is the leading cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Much of this may be attributed to systemic inflammation resulting in coronary atherosclerosis and myocarditis. Cardiac magnetic resonance imaging is the gold standard for the evaluation of cardiac structure and function, including tissue characterization, which allows for detection of myocardial edema, inflammation, and fibrosis. Advances in parametric mapping and coronary flow reserve measurement techniques have the potential to change the diagnosis, risk stratification, and management of patients with autoimmune rheumatic diseases. We provide an overview of the current evidence and suggest potential future roles for the use of comprehensive cardiac magnetic resonance in patients with autoimmune rheumatic diseases in the field of cardio-rheumatology.

Myelodysplastic syndrome (MDS) represents a spectrum of myeloid disorders occasionally linked to autoimmune diseases. Here, we present a case of a 60-year-old man demonstrating an unusual coexistence of MDS with warm-autoantibody autoimmune hemolytic anemia (wAIHA). Diagnostic evaluation, including positive direct antiglobulin testing, confirmed the autoimmune etiology of his anemia despite his low-risk MDS classification. Prompt initiation of prednisone therapy resulted in significant hematological and clinical improvement, allowing for a conservative management approach without transfusion requirements. This case underscores the importance of identifying the relationship between wAIHA and MDS, particularly in low-risk scenarios. Moreover, these findings suggest the efficacy of corticosteroids in managing autoimmune anemia in the context of concomitant wAIHA and MDS. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica spectrum disease (NMOSD) is a rare autoimmune disorder of the central nervous system characterized by optic neuritis, myelitis, or brain lesions. Its symptoms overlap with those of multiple sclerosis (MS), making a diagnosis of NMOSD challenging. Here, we report a rare case of NMOSD-induced complete spinal cord injury following COVID-19 vaccination. A 52-year-old female patient developed NMOSD-induced complete spinal cord injury after receiving their third dose of the Pfizer–BioNTech COVID-19 vaccine (BNT162b2). Despite the initial diagnosis of complete spinal cord injury, the patient underwent intensive treatment, including rituximab therapy and rehabilitation. As a result, she made a full recovery and transitioned from the ASIA Impairment Scale(AIS)-A to AIS-E. The remarkable neurological recovery from complete spinal cord injury to functional independence highlights the efficacy of a comprehensive treatment approach. In addition, this case emphasizes the need to recognize NMOSD as a potential adverse outcome of COVID-19 vaccination and emphasizes the importance of early diagnosis, timely intervention, and thorough rehabilitation for optimizing patient results. Further case reports and studies are needed to investigate the association between COVID-19 vaccination and the occurrence of NMOSD. [ABSTRACT FROM AUTHOR]

Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the landscape for the treatment of hematological malignancies, solid tumors, and, recently, autoimmune disorders. The BTK receptor is expressed in several hematopoietic cells such as macrophages, neutrophils, mast cells, and osteoclasts. Similarly, the BTK receptor is involved in signaling pathways such as chemokine receptor signaling, Toll-like receptor signaling, and Fc receptor signaling. Due to their unique mechanism, these agents provide a diverse utility in a variety of disease states not limited to the field of malignant hematology and are generally well-tolerated. [ABSTRACT FROM AUTHOR]

Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance. [ABSTRACT FROM AUTHOR]

Autoimmune disorders (AD) comprise various heterogeneous pathologies which have been associated with the development of cardiovascular disease (CVD). The pathophysiological mechanisms interrelating these clinical entities are complex and are based on proinflammatory processes mediated by the immune system. Rheumatoid arthritis, systemic lupus erythematosus, and other AD have been described to lead to a systemic inflammatory state capable of leading to endothelial dysfunction, cardiac remodeling, thrombosis, and other deleterious processes which affect the cardiovascular system. In recent years. High-quality clinical and epidemiological evidence has allowed the confirmation of the relationship between AD and CVD, highlighting the duration and inflammatory activity of the AD as key risk factor for cardiovascular events and mortality. It is important that specialists diagnose and evaluate these risk factors in patients with AD, in order to carry out an efficacious and opportune therapeutic approach looking to reduce cardiovascular morbidity and mortality. The objective of this review article is to describe the molecular mechanisms linking AD with CVD, and examine the scientific support establishing the clinical relationship between both pathologies. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a complex multisystem, autoimmune disorder. The disease involves multiple inflammatory and immune pathways, posing several treatment challenges. The role of B cells in the pathogenesis and disease activity of SLE is well described, and treatments targeting B cells are now well established. Despite advances in therapeutics for SLE, the clinical course of SLE can be associated with significant morbidity and mortality. For many individuals, the management of SLE requires lifelong immunosuppression. Chimeric antigen receptor (CAR) T cell therapy is an emerging treatment for haematological malignancies that uses CAR T cells to target CD19+ B lymphocytes. CAR T cell therapy has shown promising results in murine models of SLE, and a case report and subsequent case series in people with SLE reporting drug-free remission following CAR T cell therapy against CD19+ B cells have recently been published. This review discusses CAR T cell therapy, comparing it with established B cell depletion therapies, such as rituximab, and exploring its safety, limitations and promise in the management of patients with SLE. [ABSTRACT FROM AUTHOR]

Autoimmune disorders (AD) represent a heterogeneous group of multifactorial chronic conditions, which are triggered secondary to the loss of self-antigen tolerance. Their etiology involves genetic, epigenetic, and environmental factors; however, AD cannot be explained by these factors alone. Recent studies have shown increasing stress levels in industrialized countries and also increasing trends in the prevalence of autoimmune diseases. The oral mucosa is extremely responsive to emotional influences such as stress, anxiety and depression. Therefore, oral diseases can appear as a direct expression of emotions or indirectly, due to various psychological mechanisms. The aim of this study is to find and present possible correlations in order to support the hypothesis that psychogenic factors can play a significant role in the etiopathogenesis of autoimmune disorders in the oral cavity. The review is focused on clarifying epidemiology, etiology, pathogenesis, course, clinical signs, and management of oral lichen planus, recurrent aphthous stomatitis, psoriasis, muco-membranous pemphigoid, pemphigus, and erythema multiforme. Existing literature suggests bidirectional links between psychogenic factors and autoimmune diseases, which influence patients' psychological well-being and quality of life. Consequently, research and medical practice must continue investigations related to the proper diagnosis and clinical management of these conditions. The first signs of several diseases first appear in the oral cavity, which means that dentists can play an important role in the early diagnosis and treatment of AD oral. Although the role of psychological factors in the etiopathogenesis of AD is still underestimated, a holistic multidisciplinary approach should be implemented to provide for these health problems an appropriate diagnostic and therapeutic procedures. [ABSTRACT FROM AUTHOR]

Background: Stiff Person Syndrome Spectrum Disorders (SPSD) are a group of rare neurological disorders that can present alongside other autoimmune conditions. However, not much is known about the breadth of non-neurological autoantibodies seen in SPSD nor the observed prevalence of co-existing autoimmune comorbidities and their impact on SPSD. Objective: This study aimed to investigate the prevalence of non-neurological autoantibodies and associated conditions in a large cohort of people with SPSD. Methods: A retrospective review of 205 patients with suspected/definitive SPSD seen at Johns Hopkins Hospital from 1997 to 2023 was performed as part of an ongoing, observational study. Relevant demographics, clinical data (e.g., SPSD phenotypes, comorbid conditions, and dates of diagnoses), and laboratory values were collected from electronic medical records. Lab values were excluded if completed within 6 months of receiving intravenous immunoglobin treatment. Summary statistics were performed and assessment for any associations between autoimmune comorbidities and disease burden (modified Rankin score [mRS] and ambulation status) was performed. Results: The majority of participants had classic SPS (66%), followed by SPSplus (18%) and PERM (6%) with less than 5% each of the remaining phenotypes and suspected SPS. The average age at symptom onset in this cohort was 44.1 ± 14.5 years (mean ± standard deviation). The majority of the cohort was white (66%) and female patients (75%). The mean mRS was 2.5, and over 70% required assistive devices for ambulation. The most commonly identified nonneurological autoantibodies were anti-nuclear (ANA) (31%), thyroperoxidase (30%), thyroglobulin (20%), and anti-parietal cell (18%) autoantibodies. The most common comorbid autoimmune conditions were autoimmune thyroiditis (38%), insulin-dependent diabetes mellitus (26%), and pernicious anemia (10%). Having more autoimmune comorbidities was weakly associated with higher mRS and a greater need for ambulatory assistance. Conclusion: The results of this study will hopefully help promote awareness of which autoantibody and medical comorbidity clinicians should be aware of and monitor people with SPSD. Further research is needed to identify if poorly controlled non-neurological autoimmune disorders contribute to disease burden in SPSD and/or if the timing of being diagnosed with one of these conditions plays a role in future disability. [ABSTRACT FROM AUTHOR]

Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a "normal" version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA, and many more are under development. No GE product has been approved globally; however, critical regulatory agencies are encouraging their entry, as evidenced by the FDA issuing a guideline specific to GE products. The potential of GE in treating diseases far supersedes any other modality conceived in history. Still, it also presents unparalleled risks—from off-target impact, delivery consistency and long-term effects of gene-fixing leading to designer babies and species transformation that will keep the bar high for the approval of these products. These challenges will come to the light of resolution only after the FDA begins approving them and opening the door to a revolution in treating hundreds of untreatable diseases that will be tantamount to a revolution in the making. This article brings a perspective and a future analysis of GE to educate and motivate developers to expand GE products to fulfill the needs of patients. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the world's most common treatable neuropathy which usually responds to immunosuppressive treatment. Autologous hematopoietic stem cell transplantation (aHSCT) is an intense way of inducing immunosuppression. Objective: We analyze the evolution of CIDP patients treated with aHSCT in our center. Methods: Between 2018 and 2023, persons with CIDP were prospectively autografted employing the "Mexican method" to conduct grafts on an outpatient basis, employing cyclophosphamide 200 mg/Kg and rituximab 1000 mg. The protocol is registered in ClinicalTrials.gov identifier NCT02674217. Results: In our center 21 autologous transplant cases were completed in 2018-2023. Seven patients provided data to assess the efficacy of the procedure. Positive responses (stabilization and/or improvement) were observed in all seven patients: Five reported improvements in the Inflammatory Neuropathy Cause and Treatment (1NCAT) score and one reported stabilization. In the Inflammatory Rasch-Built Overall Disability Scale (I-RODS) score. Median INCAT score was 5 (range 1-9), whereas median I-RODS score was 24 (range 11 -29). Five patients (71%) reported improvement in the INCAT score, one reported stabilization and one informed worsening; concerning the l-RODS score 5 (71%) informed improvement, whereas two reported stabilization. Conclusion: aHSCT conducted fully in an outpatient basis, employing the conditioning regimen of the "Mexican method" appears to be a feasible therapeutic option for persons with CIDP. Additional studies are needed to confirm these observations. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 can trigger autoimmune central nervous system (CNS) diseases in genetically susceptible individuals, a mechanism poorly understood. Molecular mimicry (MM) has been identified in other viral diseases as potential triggers of autoimmune CNS events. This study investigated if MM is the process through which SARS-CoV-2 induces the breakdown of immune tolerance. The frequency of autoimmune CNS disorders was evaluated in a prospective cohort with patients admitted to the COVID-19 Intense Care Unity (ICU) in Rio de Janeiro. Then, an in silico analysis was performed to identify the conserved regions that share a high identity between SARS-CoV-2 antigens and human proteins. The sequences with significant identity and antigenic properties were then assessed for their binding capacity to HLA subtypes. Of the 112 patients included, 3 were classified as having an autoimmune disorder. A total of eleven combinations had significant linear and three-dimensional overlap. NMDAR1, MOG, and MPO were the self-antigens with more significant combinations, followed by GAD65. All sequences presented at least one epitope with strong or intermediate binding capacity to the HLA subtypes selected. This study underscores the possibility that CNS autoimmune attacks observed in COVID-19 patients, including those in our population, could be driven by MM in genetically predisposed individuals. [ABSTRACT FROM AUTHOR]

A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system. [ABSTRACT FROM AUTHOR]