Rheumatoid Arthritis: Pathogenic Roles of Diverse Immune Cells

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease associated with synovial tissue proliferation, pannus formation, cartilage destruction, and systemic complications. Currently, advanced understandings of the pathologic mechanisms of autoreactive CD4+ T cells, B cells, macrophages, inflammatory cytokines, chemokines, and autoantibodies that cause RA have been achieved, despite the fact that much remains to be elucidated. This review provides an updated pathogenesis of RA which will unveil novel therapeutic targets.

Inflammasome and Its Therapeutic Targeting in Rheumatoid Arthritis

Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is critically involved in innate inflammatory response. Excessive or abnormal activation of inflammasomes has been shown to contribute to the development of various diseases including autoimmune diseases, neurodegenerative changes, and cancers. Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease, in which inflammasome activation plays a pivotal role in immune dysregulation and joint inflammation. This review summarizes recent findings on inflammasome activation and its effector mechanisms in the pathogenesis of RA and potential development of therapeutic targeting of inflammasome for the immunotherapy of RA.

Mitigation of Equine Recurrent Uveitis Through Topical Suppressor of Cytokine Signaling-1 Mimetic Peptide: Open Label Safety and Efficacy Pilot Study

Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease, and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness. Notably, suppressor of signaling-1 (SOCS1), which naturally limits the activation of Jak2 through binding interactions, is often deficient in autoimmune disease patients. Significantly, we previously showed that topical administration of a SOCS1 peptide mimic (SOCS1-KIR) mitigated induced rodent uveitis. In this pilot study, we test the potential to translate the therapeutic efficacy observed in experimental rodent uveitis to equine patient disease. Through bioinformatics and peptide binding assays we demonstrate putative binding of the SOCS1-KIR peptide to equine Jak2. We also show that topical, or intravitreal injection of SOCS1-KIR was well tolerated within the equine eye through physical and ophthalmic examinations. Finally, we show that topical SOCS1-KIR administration was associated with significant clinical ERU improvement. Together, these results provide a scientific rationale, and supporting experimental evidence for the therapeutic use of a SOCS1 mimetic peptide in RU.

Autoimmune Polyglandular Syndrome Type 3-D

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies against cell nuclei and involves many organ systems in the body. The etiopathology of SLE is thought to involve complex and multifactorial interactions between genetic variation and environmental factors. Hyperthyroidism is a disease due to increased thyroid hormone function followed by signs and symptoms that affect the body's metabolic system. Graves' disease is an autoimmune disease characterized by the presence of antibodies to TSHR (TRAb). Several coexisting autoimmune diseases have been classified under different syndromes. Case Presentation: A woman, 29 years-old, came to office with complaint of chest palpitation. Patient had history of fever, joint pain, hair loss, and malar rash. Patient had been diagnosed with hyperthyroidism for 4 years and regularly taking propylthiouracil 100 mg and propranolol 10 mg. Titer ANA Test 1/100, Anti ds-DNA 68.08, C3-Complement 93 (N: 83-193), C4-Complement 11.2 (N: 15-57), Free T3 7.79 (N: 1.71-3.71), Free -T4 2.50 (N: 0.70-1.48), TSHs 0.0001 (N: 0.350-4.94), TRAb 3.38 (N: < 1.75). Patient was diagnosed with systemic lupus erythematosus (SLE) and graves’ disease. Patient treated with methimazole 10 mg, propranolol 10 mg, myfortic 360 mg, and methylprednisolone 4 mg. Conclusion: Autoimmune Polyendocrine Syndromes (APS) was at first characterized as different endocrine organ diseases related to an immune system disease in a subject. Hence, affiliation between illnesses in APS was noted not to be irregular but in specific combinations in which a few non-endocrine immune system diseases were moreover portion of the disorders.

Pediatric Autoimmune Encephalitis Following COVID-19 Infection

Similar to the pathogenesis of autoimmune disease, SARS-CoV-2 (COVID-19) infection has been shown to be associated with dysregulated and persistent inflammatory reactions and production of some antibodies. We report 3 pediatric patients found to have serum SARS-CoV-2 antibodies who presented with neurologic findings suggestive of postinfectious autoimmune-mediated encephalitis. All 3 cases showed lymphocytic pleocytosis on cerebrospinal fluid studies and marked improvement in neurologic symptoms after high-dose intravenous corticosteroids. The manifestations of SARS-CoV-2 infection in the pediatric population are still an evolving area of study, and these cases suggest autoimmune-mediated encephalitis as yet another SARS-CoV-2 related complication.

Recurrence of Anti-semaphorin-3B Mediated Membranous Nephropathy after Kidney Transplantation

Background: Membranous nephropathy (MN) is rare in pediatric patients, although its diagnosis may be underestimated in children who are responsive to corticosteroid therapy prescribed for a suspicion of minimal change disease. It is most often associated with an autoimmune disease, predominantly lupus. We previously reported the occurrence of early onset membranous nephropathy associated with Semaphorin 3B in 9 children and 2 adults. Methods: Biopsies were performed on native kidney and at 1 and 5 months after transplantation. Semaphorin 3B antigen was detected in immune deposits by immunohistochemistry and confocal microscopy on paraffin-embedded biopsies. Anti-Semaphorin antibodies were detected by Western blot and analyzed sequentially. Results: We report the first case of early recurrence after transplantation in a 7-year old boy who presented with severe nephrotic syndrome and advanced kidney failure. There was no evidence of hereditary or associated autoimmune disease. Abundant, almost coalescent deposits were seen by electron microscopy and bright granular, subepithelial staining was observed for Semaphorin 3B antigen. Western blot analysis of serum revealed antiSemaphorin 3B antibodies. Recurrence of MN occurred 25 days after transplantation and manifested as nephrotic range proteinuria despite conventional immunosuppressive therapy. Kidney biopsies confirmed histological MN recurrence with colocalization of Semaphorin 3B antigen and IgG (1). The patient was treated with rituximab. Anti-Semaphorin 3B antibodies, which were detected at transplantation, were not detected 40 days after rituximab. Conclusion: This case provides evidence that anti-Semaphorin 3B antibodies are pathogenic and should be monitored in patients with membranous nephropathy.

Polyglandular Autoimmune Syndrome Type 3D : A Case Report

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies against cell nuclei and involves many organ systems in the body. The etiopathology of SLE is thought to involve complex and multifactorial interactions between genetic variation and environmental factors. Hyperthyroidism is a disease due to increased thyroid hormone function followed by signs and symptoms that affect the body's metabolic system. Graves' disease is an autoimmune disease characterized by the presence of antibodies to TSHR (TRAb). Several coexisting autoimmune diseases have been classified under different syndromes. Autoimmune Polyglandular Syndrome (PGAS),Case Presentation: A woman, 29 years-old, came to office with complaint of chest palpitation. Patient had history of fever, joint pain, hair loss, and malar rash. Patient had been diagnosed with hyperthyroidism for 4 years and regularly taking propylthiouracil 100 mg and propranolol 10 mg. Titer ANA Test 1/100, Anti ds-DNA 68.08, C3-Complement 93 (N: 83-193), C4-Complement 11.2 (N: 15-57), Free T3 7.79 (N: 1.71-3.71), Free -T4 2.50 (N: 0.70-1.48), TSHs 0.0001 (N: 0.350-4.94), TRAb 3.38 (N: &lt; 1.75). Patient was diagnosed with systemic lupus erythematosus (SLE) and grave's disease. Patient treated with methimazole 10 mg, propranolol 10 mg, myfortic 360 mg, and methylprednisolone 4 mg.Conclusion: Autoimmune Polyendocrine Syndromes (APS) was at first characterized as different endocrine organ diseases related to an immune system disease in a subject. Hence, affiliation between illnesses in APS was noted not to be irregular but in specific combinations in which a few non-endocrine immune system diseases were moreover portion of the disorders.

Exposure to silicates and systemic autoimmune-related outcomes in rodents: a systematic review

Background Autoimmunity can result from the interplay between genetic background and effects of environmental and/or occupational exposure to hazardous materials. Several compounds, including silica dust, have been linked with systemic autoimmunity and systemic autoimmune diseases, based on epidemiological evidence. For asbestos, a strong link with systemic autoimmune diseases does not yet exist, however, several studies have documented features of autoimmunity following asbestos exposure. Even so, human studies are limited in their ability to identify and examine isolated exposures, making it difficult to demonstrate causation or to assess pathogenic mechanisms. Therefore, this systematic review examines the existing animal evidence regarding autoimmunity and exposure to silicates (silica and asbestos). Methods PubMed and EMBASE were systematically searched for peer-reviewed studies examining systemic autoimmune disease-related outcomes after silicate exposure in rodents. Literature databases were searched up to September 2021 for studies written in English and where the full text was available. Search strings were established based on a PECO (Population, Exposure, Comparator, Outcome) format. After title, abstract, and full-text screening, thirty-four studies were identified for further analysis. Quality assessment through ToxR tool and qualitative analysis of the results was performed. Results Although there was significant heterogeneity in the included studies in terms of exposure protocol and genetic background of the rodent models used, it was noted that both genetic background and exposure to silicates [(crystalline) silica and asbestos] are highly relevant to the development of (sub-) clinical systemic autoimmune disease. Conclusion Parallels were observed between the findings from the animal (this review) and human (epidemiological) studies, arguing that experimental animal models are valuable tools for examining exacerbation or development of autoimmune disease after silicate exposure. However, genetic background and synergism between exposures should be considered in future studies.