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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 |
Int J Mol Sci
August 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
VEXAS syndrome (Vacuoles, E1-enzyme, X-linked, Autoinflammation, and Somatic) is a recently identified late-onset autoinflammatory disorder characterized by a unique interplay between hematological and inflammatory manifestations. It results from somatic mutations in the gene, located on the short arm of the X chromosome. Initially, females were considered mere carriers, with the syndrome primarily affecting males over 50.
View Article and Find Full Text PDFJ Hum Immun
September 2025
Department of Pediatrics, Division of Rheumatology/Immunology, Washington University in St. Louis, St. Louis, MO, 63119.
Inborn errors of immunity (IEI) are monogenic disorders of the immune system that frequently present with autoimmunity or autoinflammation, necessitating multi-specialty care. In many cases, patients may present for rheumatologic evaluation prior to a genetic diagnosis, highlighting the need for recognition of an underlying IEI with immune dysregulation. Here, we review IEI that can present with rheumatologic and autoimmune complications and the role of genetic testing for establishing a molecular diagnosis and devising personalized treatment plans to improve patient outcomes.
View Article and Find Full Text PDFAutoimmun Rev
August 2025
Institut Imagine, INSERM U1163, CNRS ERL 8254, Sorbonne Paris-Cité, Laboratoire d'Excellence GR-Ex, Université Paris Cité, Paris, France.
Systemic AutoInflammatory Diseases (SAIDs), AutoImmune Diseases (AIDs), and Primary Immune Deficiencies (PIDs) were formely considered independent, even opposing, conditions. SAIDs were associated with the innate immune system, involving dysregulation of inflammation and recurrent episodes of systemic inflammation without an infectious process. Their original definition did not involve autoreactive cells or autoantibodies.
View Article and Find Full Text PDFmBio
August 2025
Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
Unlabelled: Sensing of viral double-stranded RNA (dsRNA) by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases, but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences.
View Article and Find Full Text PDFJ Transl Autoimmun
December 2025
Laboratory of Clinical Immunology, Infection and Autoimmunity (LICIA), Faculty of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
Inborn Errors of Immunity (IEI) are a heterogeneous group of genetic disorders characterized by increased susceptibility to infections and immune dysregulation, including autoimmunity and autoinflammation. Despite their clinical significance, data on autoimmune manifestations in Moroccan pediatric patients with IEI remain limited. This study aims to investigate the prevalence, spectrum, and clinical patterns of autoimmune manifestations in pediatric patients with IEI in Morocco.
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