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The pathogenesis of alopecia areata, a common autoimmune non-scarring alopecia, remains unclear・ Current studies have shown that the loss of immune privilege of hair follicles due to the up-regulation of MHC molecules and the decrease in immunosuppressive molecules leads to the exposure of self-antigens in the affected area・ This triggers the infiltration of immune cells (such as CD8 + T cells, NK cells, plasmacytoma dendritic cells, and mast cells) around the hair bulb ・ Various immune cells and related cytokines participate in the pathogenesis and development of this disease through diverse signaling pathways・ Due to its complex pathogenesis and diverse clinical manifestations, there are challenges in the diagnosis and treatment in clinic・ This paper aims to provide a comprehensive review on recent advances in understanding the immunological pathogenesis of alopecia areata by focusing on mechanisms underlying immune privilege loss around hair follicles and the interaction between various immune cells in the microenvironment for a deeper understanding of its pathogenesis・ It also seeks to explore new research directions and potential treatment strategies. [ABSTRACT FROM AUTHOR]

Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of chronic inflammatory diseases or autoimmune reactions is a major source of concern and affects the quality of life of patients. Chronic inflammatory or autoimmune diseases are associated with many diseases in humans, including asthma, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and cancer. Splenic tyrosine kinase (SYK) is a non–receptor tyrosine kinase that plays an important role in immune receptor signalling in immune and inflammatory responses. Methods: This is a review article in which we searched for keywords "splenic tyrosine kinase", "inflammation" and "autoimmune diseases" in published literature such as Pubmed and Web of Science to collect relevant information and then conducted a study focusing on the latest findings on the involvement of SYK in chronic inflammatory or autoimmune diseases. Results: This paper reviews the regulation of Fcγ, NF–κB, B cell and T cell–related signalling pathways by SYK, which contributes to disease progression in chronic inflammatory and autoimmune diseases such as airway fibrosis, inflammatory skin disease and inflammatory bowel disease. Conclusion: This paper shows that SYK plays an important role in chronic inflammatory and autoimmune diseases. syk targets hematological, autoimmune and other inflammatory diseases and therefore, inhibition of SYK expression or blocking its related pathways may provide new ideas for clinical prevention and treatment of inflammatory or autoimmune diseases. [ABSTRACT FROM AUTHOR]

Autoimmune diseases are characterized by a breakdown of immune tolerance, leading to inflammation and irreversible end-organ tissue damage. Platelet extracellular vesicles are cellular elements that are important in blood circulation and actively participate in inflammatory and immune responses through intercellular communication and interactions between inflammatory cells, immune cells, and their secreted factors. Therefore, platelet extracellular vesicles are the "accelerator" in the pathological process of autoimmune diseases; however, this robust set of functions of platelet extracellular vesicles has also prompted new advances in therapeutic strategies for autoimmune diseases. In this review, we update fundamental mechanisms based on platelet extracellular vesicles communication function in autoimmune diseases. We also focus on the potential role of platelet extracellular vesicles for the treatment of autoimmune diseases. Some recent studies have found that antiplatelet aggregation drugs, specific biological agents can reduce the release of platelet extracellular vesicles. Platelet extracellular vesicles can also serve as vehicles to deliver drugs to targeted cells. It seems that we can try to silence or inhibit microRNA carried by platelet extracellular vesicles transcription and regulate the target cells to treat autoimmune diseases as platelet extracellular vesicles can transfer microRNA to other cells to regulate immune-inflammatory responses. Hopefully, the information presented here will provide hope for patients with autoimmune diseases. Autoimmune diseases patients are characterized by autoimmune disorders, whose immune system cannot distinguish between auto- and foreign-antigens. Autoimmune diseases is the third significant disease threatening human health after cardiovascular disease and cancer. However, the exact etiology of autoimmune diseases has yet to be fully elucidated. Several studies have shown that platelet extracellular vesicle content is elevated in multiple autoimmune disorders and positively correlates with disease activity. However, our knowledge about the details of the mechanisms still remains limited and fragmentary. This article updates the communication function of platelet extracellular vesicles in accelerating autoimmune and inflammatory responses. The interesting thing is every coin has two sides. We put forward a new treatment idea for AD based on the particular volume and powerful intercellular communication function of platelet extracellular vesicles. Inhibition of the communication function of platelet extracellular vesicles seems to be considered in the future, or silence or block miRNA of platelet extracellular vesicles involved in the pathogenesis of AD. We can even use it as a drug carrier to deliver the drug to the relevant target cells, thereby enhancing the role of the medicine in regulating immune response and inhibiting inflammation. This paper not only provides a deeper understanding of the pathogenesis of autoimmune diseases but also provides theoretical support for the use of platelet extracellular vesicles to achieve targeted therapy. [ABSTRACT FROM AUTHOR]

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them. [ABSTRACT FROM AUTHOR]

A comprehensive search of published literature in brain volumetry was conducted in three autoimmune diseases — systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ulcerative colitis (UC) — with the intention of performing a meta-analysis of published data. Due to the lack of data in RA and UC, the reported meta-analysis was limited to SLE. The MEDLINE database was searched for studies from 1988 to March 2022. A total of 175 papers met the initial inclusion criteria, and 16 were included in a random-effects meta-analysis. The reduction in the number of papers included in the final analysis is primarily due to the lack of overlap in measured and reported brain regions. A significantly lower volume was seen in patients with SLE in the hippocampus, corpus callosum, and total gray matter volume measurements as compared to age- and sex-matched controls. There were not enough studies to perform a meta-analysis for RA and UC; instead, we include a summary of published volumetric studies. The meta-analyses revealed structural brain abnormalities in patients with SLE, suggesting that lower global brain volumes are associated with disease status. This volumetric difference was seen in both the hippocampus and corpus callosum and total gray matter volume measurements. These results indicate both gray and white matter involvements in SLE and suggest there may be both localized and global reductions in brain volume. [ABSTRACT FROM AUTHOR]

Simple Summary: We have identified what is most likely a hereditary inflammatory muscle disease within the Dutch dog breed 'Het Nederlandse Kooikerhondje'. The clinical signs are either locomotory, dysphagia, or a combination of these signs. In most dogs, the muscular enzyme creatine kinase (CK) was elevated. Histopathology revealed an inflammatory myopathy. The Dutch Kooiker dog (het Nederlandse Kooikerhondje) is one of nine Dutch dog breeds. As of 1960, a number of heritable diseases have been noted in this breed. One is an inflammatory myopathy that emerged in 1972, with numbers of affected dogs gradually increasing during the last few decades. The objective of this paper is to describe clinical signs, laboratory results, electromyography and histopathology of the muscle biopsies of the affected dogs. Method: Both retrospectively as well as prospectively affected Kooiker dogs were identified and categorized using a Tiered level of Confidence. Results: In total, 160 Kooiker dogs—40 Tier I, 33 Tier II and 87 Tier III—were included. Clinical signs were (1) locomotory problems, such as inability to walk long distances, difficulty getting up, stiff gait, walking on eggshells; (2) dysphagia signs such as drooling, difficulty eating and/or drinking; or (3) combinations of locomotory and dysphagia signs. CK activities were elevated in all except for one dog. Histopathology revealed a predominant lymphohistiocytic myositis with a usually low and variable number of eosinophils, neutrophils and plasma cells. It is concluded that, within this breed, a most likely heritable inflammatory myopathy occurs. Further studies are needed to classify this inflammatory myopathy, discuss its treatment, and unravel the genetic cause of this disease to eradicate it from this population. [ABSTRACT FROM AUTHOR]

Introduction: The Profile of Fatigue and Discomfort–Sicca Symptoms Inventory–Short Form (PROFAD-SSI-SF) is a 19-item patient-reported outcome (PRO) measure to assess pain, fatigue, and dryness in patients with primary Sjögren's syndrome (pSS). This analysis identified concepts important to measure, and evaluated the content validity and measurement properties of the PROFAD-SSI-SF, in patients with pSS. Methods: Qualitative analyses (GSK Study 208396) used transcripts from an online concept elicitation (CE) discussion forum with patients with pSS and interviews with key opinion leaders (KOLs) to finalize a disease model depicting important concepts for patients with pSS. Cognitive debriefing (CD) interviews with patients with pSS were conducted to further evaluate the content validity of the PROFAD-SSI-SF. Quantitative analyses (GSK Study 213253) used post hoc analyses of blinded data from a phase 2 trial to assess PROFAD-SSI-SF measurement properties. Results: The CE discussion forum (N = 46) revealed dryness (oral 87.0%, ocular 73.9%, cutaneous 37.0%, vaginal 23.9%, nasal 15.2%, otic 6.5%), pain (89.1%), and fatigue (87.0%) as the most reported symptoms. KOLs (N = 5) found the concepts identified in the disease model accurate and understandable, and confirmed that PROs used in pSS studies should focus on dryness, joint pain, and fatigue. In the CD interviews (N = 20), of the 19 participants asked, all found the PROFAD-SSI-SF easy to understand, and 14/19 items were considered relevant by ≥ 18/20 participants. The quantitative analyses found an acceptable fit of the PROFAD-SSI-SF factor structure, with adequate internal consistency, test–retest reliability, convergent validity with other PRO measures, known-groups validity with Patient Global Assessment, and ability to detect change in patients with pSS. Conclusion: The final disease model confirmed that the PROFAD-SSI-SF assesses concepts that are relevant and important to patients with pSS. Our findings support the content validity and measurement properties of the PROFAD-SSI-SF as a fit-for-purpose PRO measure appropriate for use in clinical trials in patients with pSS. Clinical Trial Registration number for the phase 2 trial: Clinicaltrials.gov NCT02631538 Plain Language Summary: Primary Sjögren's syndrome (pSS) is a disease where the immune system attacks the body, causing a number of symptoms, most notably dryness (sicca) of the eyes and mouth. The Profile of Fatigue and Discomfort–Sicca Symptoms Inventory–Short Form (PROFAD-SSI-SF) is a questionnaire for patients with pSS that asks about their symptoms. This paper evaluates how relevant the PROFAD-SSI-SF questions are to patients with pSS, and how consistently and accurately the questionnaire can measure changes in their symptoms. We reviewed information about the symptoms and impacts of pSS from an online discussion forum for patients with pSS. Patients said that dryness, fatigue, and pain were the symptoms that most affected their day-to-day lives and well-being. We combined this information with previous research on pSS to design a diagram explaining the key symptoms and day-to-day impacts of pSS, which was reviewed by five experts in pSS. In doing so, we aimed to confirm whether the most important things to patients about living with pSS are asked in the PROFAD-SSI-SF questionnaire. Next, we asked 20 patients with pSS how easy they found the PROFAD-SSI-SF to complete and if any important concepts were missing; they reported that the PROFAD-SSI-SF was easy to fill in and that the important questions were included. Finally, we looked at data from a clinical trial that used the PROFAD-SSI-SF and found it accurately measures changes in symptoms of patients with pSS. This means that the PROFAD-SSI-SF could be used in clinical trials to help assess new medicines for pSS. [ABSTRACT FROM AUTHOR]

This paper presents a model‐based method for clustering multivariate binary observations that incorporates constraints consistent with the scientific context. The approach is motivated by the precision medicine problem of identifying autoimmune disease patient subsets or classes who may require different treatments. We start with a family of restricted latent class models or RLCMs. However, in the motivating example and many others like it, the unknown number of classes and the definition of classes using binary states are among the targets of inference. We use a Bayesian approach to RLCMs in order to use informative prior assumptions on the number and definitions of latent classes to be consistent with scientific knowledge so that the posterior distribution tends to concentrate on smaller numbers of clusters and sparser binary patterns. The paper derives a posterior sampling algorithm based on Markov chain Monte Carlo with split‐merge updates to efficiently explore the space of clustering allocations. Through simulations under the assumed model and realistic deviations from it, we demonstrate greater interpretability of results and superior finite‐sample clustering performance for our method compared to common alternatives. The methods are illustrated with an analysis of protein data to detect clusters representing autoantibody classes among scleroderma patients. [ABSTRACT FROM AUTHOR]

Purpose: This paper is a scoping review of research on multiple sclerosis (MS)‐associated uveitis to determine its epidemiology, pathophysiology, clinical features and treatment. Methods: A comprehensive search of the medical databases MEDLINE (PubMed), EMBASE, Web of Science and Cochrane was carried out on 25 November 2019, to identify papers published between 1980 and 2019 that focus on patients with MS‐associated uveitis. Results: Based on large cohort studies (n ≥ 1000), the prevalence of uveitis in patients with MS is estimated to be 0.53–1.34% (mean = 0.83%), and MS is diagnosed in 0.52–3.20% (mean = 1.30%) of patients with uveitis. The condition is most frequent among middle‐aged women. Patients usually complain of floaters and/or blurred vision, with bilateral intermediate uveitis (with retinal vasculitis) as the most frequent ophthalmological finding. Both MS and intermediate uveitis are associated with HLA‐DRB1*15:01 and IL‐2RA gene polymorphism rs2104286 A > G, suggesting a common genetic background. T cells, and possibly B cells, play an important role in both autoimmune disorders. Multiple sclerosis (MS)‐related uveitis is classically treated as non‐infectious uveitis, with corticosteroids as the first treatment step. Other treatments include immunosuppressants, cryotherapy, laser photocoagulation and vitrectomy. These treatment options have a limited, if any, effect on the course of MS and can be complicated by side‐effects. As treatment strategies for MS have increased in the last decade, it would be interesting to evaluate the efficacy of these new treatments during the course of uveitis. Moreover, the correlation between retinal periphlebitis and MS could be established more accurately with the recently developed techniques of wide‐field fluorescein angiography in a large cohort of MS patients. Conclusion: MS‐associated uveitis is a rare, highly discussed pathology about which much is still unknown. Large epidemiological studies and extrapolation of new MS treatments to this condition are warranted. [ABSTRACT FROM AUTHOR]

CD247, which is also known as CD3ζ, CD3H, CD3Q, CD3Z, IMD25, T3Z and TCRZ, encodes CD3ζ protein, which is expressed primarily in natural killer (NK) and T cells. Since the discovery of the ζ peptide in 1986, it has been continuously investigated. In this paper, we review the composition, molecular mechanisms and regulatory factors of CD247 expression in T cells; and review the autoimmune diseases, tumours and inflammatory diseases associated with CD247, providing a detailed and comprehensive reference for further research on the mechanism of CD247 and related diseases. [ABSTRACT FROM AUTHOR]

Numerous immunotherapeutic agents, such as immune checkpoint inhibitors (ICIs), have been approved for the treatment of genitourinary (GU) malignancies. While ICIs have improved treatment outcomes and expanded treatment options, they can cause immune-related adverse events (irAEs). The scope of irAEs is broad, and this paper aims to review the rheumatologic side effects associated with immunotherapy drugs approved for bladder cancer and renal cell carcinoma. IrAEs are graded by the common terminology criteria for adverse events (CTCAE), which ranges from 1 to 5. The management of irAEs includes corticosteroids or other immunosuppressive therapies, and it may require discontinuation of immunotherapy. Several real world experience studies suggest that most patients with pre-existing autoimmune diseases treated with ICI did not have to discontinue treatment due to immune-mediated side effects. While data suggest autoimmune side effects are manageable, patients with pre-existing autoimmune diseases are often excluded from immunotherapy clinical trials. Better understanding of these irAEs will improve its safety and expand its use in those with underlying autoimmune disease. [ABSTRACT FROM AUTHOR]

Objective: Behçet's disease (BD) is a multisystem inflammatory disease that affects patients along the historic silk road. Thus far, the pathogenesis of the disease has proved elusive due to the complex genetic interactions of the disease. In this paper, we seek to clarify the genetic factors of the disease while also uncovering other diseases of interest that present with a similar genotype as BD. Results: To do this, we employ a convergent functional genomics approach by leveraging the hierarchical similarity tool available in Geneweaver. Through our analysis, we were able to ascertain 7 BD consensus genes and 16 autoimmune diseases with genetic overlap with BD. The results of our study will inform further research into the pathogenesis of Behçet's disease. [ABSTRACT FROM AUTHOR]

Autoimmune diseases (AIDs) are a series of immune-mediated lethal diseases featured by over-activated immune cells attacking healthy self-tissues and organs due to the loss of immune tolerance, which always causes severe irreversible systematical organ damage and threatens human health heavily. To date, there are still no definitive cures for the treatment of AIDs due to their pathogenesis has not been clearly understood. Besides, the current clinical treatments of AIDs majorly rely on glucocorticoids and immune suppressors, which can lead to serious side effects. In the past years, there are increasing studies demonstrating that an imbalance of gut microbiota is intimately related to the pathogenesis of various AIDs, shedding light on the development of therapeutics by targeting the gut microbiota for the management of AIDs. Among all the approaches targeting the gut microbiota, fecal microbiota transplantation (FMT) has attracted increasing interest, and it has been proposed as a possible strategy to intervene in the homeostasis of gut microbiota for the treatment of various diseases. However, despite the reported good curative effects and clinical studies conducted on FMT, the detailed mechanisms of FMT for the effective treatment of those diseases have not been figured out. To fully understand the mechanisms of the therapeutic effects of FMT on AIDs and improve the therapeutic efficacy of FMT treatment, a systematic review of this topic is necessary. Hence, in this review paper, the potential mechanisms of FMT for the treatment of various AIDs were summarized, including promotion, shaping, activation, or inhibition of the host immune system via the interactions between the microorganisms and the gut immune system, gut-brain, gut-liver, gut-kidney axis, and so on. Then, applications of FMT for the treatment of various AIDs were detailed presented. Finally, the current challenges and potential solutions for the development of FMT formulations and FMT therapeutics were comprehensively discussed. • The potential mechanisms of FMT in the treatment of autoimmune diseases were summarized. • Applications of FMT for the treatment of various autoimmune diseases were detailedly reviewed. • The current challenges and potential solutions for the development of FMT therapeutic strategies were comprehensively discussed. [ABSTRACT FROM AUTHOR]

T follicular helper (Tfh) cells with the phenotype of mainly expressing surface molecules C-X-C motif chemokine receptor type 5 (CXCR5), inducible co-stimulator (ICOS), secreting cytokine interleukin-21 (IL-21) and requiring the transcription factor B cell lymphoma 6 (BCL-6) have been recently defined as a new subset of CD4+ T cells. They exist in germinal centers (GCs) of lymphoid organs and in peripheral blood. With the ability to promote B cell development, GC formation and antibody production, Tfh cells play critical roles in the pathogenesis of many autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), etc. The aberrant proliferation and function of Tfh cells will cause the pathological process like autoantibody production and tissue injury. In this paper, we review the recent advances in Tfh cell biology and their roles in autoimmune diseases, with a mention of their use as therapeutic targets, which will shed more light on the pathogenesis and treatment of certain autoimmune diseases. • Tfh cells are defined as a CD4+ T cell subset that promotes B cell maturation and differentiation, antibody production and GC formation. • The pathogenesis of several autoimmune diseases is associated with Tfh cells. • Targeting Tfh cells represents new insights in the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]

The immune system is a complex interconnected network consisting of many parts including organs, tissues, cells, molecules and proteins that work together to protect the body from illness when germs enter the body. An autoimmune disease is a disease in which the body's immune system attacks healthy cells. It is known that when the immune system is working properly, it can clearly recognize and kill the abnormal cells and virus-infected cells. But when it doesn't work properly, the human body will not be able to recognize the virus-infected cells and, therefore, it can attack the body's healthy cells when there is no invader or does not stop an attack after the invader has been killed, resulting in autoimmune disease.; This paper presents a mathematical modeling of the virus-infected development in the body's immune system considering the multiple time-delay interactions between the immune cells and virus-infected cells with autoimmune disease. The proposed model aims to determine the dynamic progression of virus-infected cell growth in the immune system. The patterns of how the virus-infected cells spread and the development of the body's immune cells with respect to time delays will be derived in the form of a system of delay partial differential equations. The model can be used to determine whether the virus-infected free state can be reached or not as time progresses. It also can be used to predict the number of the body's immune cells at any given time. Several numerical examples are discussed to illustrate the proposed model. The model can provide a real understanding of the transmission dynamics and other significant factors of the virus-infected disease and the body's immune system subject to the time delay, including approaches to reduce the growth rate of virus-infected cell and the autoimmune disease as well as to enhance the immune effector cells. [ABSTRACT FROM AUTHOR]