Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity.
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http://dx.doi.org/10.1007/s12016-021-08914-w | DOI Listing |
Immunity
December 2024
Institute of Experimental Hematology, School of Medicine, Technical University of Munich, 81675 Munich, Germany; Center for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, 81675 Munich, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Max-Planck Institute of Biochemistry, 82152 Planegg, Germany. Electronic address:
B cell immunity carries the inherent risk of deviating into autoimmunity and malignancy, which are both strongly associated with genetic variants or alterations that increase immune signaling. Here, we investigated the interplay of autoimmunity and lymphoma risk factors centered around the archetypal negative immune regulator TNFAIP3/A20 in mice. Counterintuitively, B cells with moderately elevated sensitivity to stimulation caused fatal autoimmune pathology, while those with high sensitivity did not.
View Article and Find Full Text PDFClin Immunol
November 2024
Meniere's Disease Neuroscience Research Program, Faculty of Medicine & Health, School of Medical Sciences, The Kolling Institute, The University of Sydney, Sydney, New South Wales, Australia; Division of Otolaryngology, Department of Surgery, Instituto de Investigación Biosanitaria, ibs.GRANADA, Granada, Universidad de Granada, Granada, Spain; Sensorineural Pathology Programme, Centro de Investigación Biomédica en Red en Enfermedades Raras, CIBERER, Madrid, Spain.
Background: Meniere disease (MD), an inner ear disorder influenced by genetic and environmental factors, potentially leads to chronic inflammation. This study evaluates whether inflammation in MD patients is driven by allergy or autoinflammation.
Methods: 2-year longitudinal study.
Cells
November 2024
Department of Medicine, Division of Internal Medicine, Lausanne University Hospital (CHUV), University of Lausanne, 1005 Lausanne, Switzerland.
VEXAS syndrome, a monogenic X-linked disorder resulting from mutations in the UBA1 gene, has emerged as a key model for unraveling the links between systemic inflammatory or autoimmune diseases (SIAD) and myelodysplastic syndromes (MD). This syndrome is characterized by the presence of vacuoles, X-linked inheritance, autoinflammation, and somatic mutation patterns, highlighting a unique intersection between genetic and immunological dysregulation. Apart from VEXAS, 10% to 30% of individuals diagnosed with MDS exhibit SIAD phenotypes, a significant increase compared to the 5% incidence in the general population.
View Article and Find Full Text PDFAnn Hum Genet
January 2025
Pediatrics Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Introduction: Activation-induced cytidine deaminase (AID) deficiency is a rare autosomal recessive inborn error of immunity (IEI) characterized by increased susceptibility to infections, autoimmunity, and/or autoinflammation. AID plays an important role in immunoglobulin class switching and somatic hypermutation. AID deficiency patients have very low or absent levels of IgG, IgA, and IgE, while IgM level is elevated.
View Article and Find Full Text PDFArch Rheumatol
September 2024
Department of Pediatrics, Division of Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Türkiye.
Systemic autoinflammatory diseases are a group of disorders characterized by sterile episodes of inflammation resulting from defects in the innate immune system. In contrast to classical autoimmune diseases, where circulating autoantibodies and the adaptive immune system are involved, these conditions involve excessive presence of proinflammatory cytokines leading to inflammatory attacks. Excessive cytokine production, functional mutations in regulatory pathways, excessive interferon production, defects in the nuclear factor-kappa B signaling pathway, abnorARCHmal protein folding, and complement activation are the mechanisms leading to autoinflammatory diseases.
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