The Pathogenesis of Ankylosing Spondylitis: an Update

AbstractPurpose of ReviewAnkylosing spondyloarthritis (AS) is a chronic inflammatory disease that involves the axial joints and entheses. Extra-spinal manifestations such as anterior uveitis, psoriasis, and colitis also occur frequently. This review on the pathogenesis of AS includes an update on the recent discoveries within the field.Recent FindingsHLA-B*27 is still considered of major importance in the pathogenesis, and it has recently been shown to profoundly affect the gut microbiome and its metabolites and the handling of bacteria during infection. Biochemical and biophysical properties of HLA-B*27 influence its ability to misfold, to induce an endoplasmic reticulum stress response, and to promote autophagy/unfolded protein responses (UPR). HLA-B*27 free heavy chains may induce inflammation through T cells, NK cells, and myeloid cells. Induction of UPR genes results in release of tumor necrosis factor- α (TNF-α), interleukin-17 (IL-17), IL-23, and interferon-γ and increase in T helper (Th) 17 cells. Several other HLA-B and non-B molecules have been associated with AS, although their role in the pathogenesis is unknown.SummaryGenotypes of endoplasmic reticulum aminopeptidases (ERAP) 1 and 2 have been associated with alterations in the antigenic pool expressed by HLA-B*27 molecules. In the gut, innate immune cells type 3 (ILC3) influence T cell expression of IL-17 and IL-22. Gamma-delta ( γ/δ) T cells are induced by IL-23 to produce IL-17. IL...
Source: Current Rheumatology Reports - Category: Rheumatology Source Type: research

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Authors: Carli L, Calabresi E, Governato G, Braun J Abstract Spondyloarthritis (SpA) is the umbrella term for a broad spectrum of inflammatory rheumatic diseases with typical but also rather different clinical manifestations, limited laboratory abnormalities and characteristic imaging features. For classification purposes, a so-called non-radiographic form (nr-axSpA) is differentiated from a radiographic one (r-axSpA) which is almost identical to the classical ankylosing spondylitis (AS) that is genetically strongly associated with the major histocompatibility complex class 1 antigen HLA-B27. In axSpA, the axial sk...
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Pfizer Inc. (NYSE: PFE) announced the United States (U.S.) Food and Drug Administration (FDA) has approved ABRILADA™ (adalimumab-afzb), as a biosimilar to Humira® (adalimumab),(1) for the treatment of certain patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn's disease, ulcerative colitis and plaque psoriasis.(2)
Source: World Pharma News - Category: Pharmaceuticals Tags: Featured Pfizer Business and Industry Source Type: news
Objectives: To test the hypothesis that familial Mediterranean fever (FMF)-associated autoinflammation may exaggerate the tendency toward adaptive immunopathology or spondyloarthritis (SpA)-associated disorders including major histocompatibility complex (MHC) class I associated disorders but not classical MHC class II-associated disorders that exhibit transplacental autoimmunity including myasthenia gravis and pemphigus.Methods: Seven thousand seven hundred forty-seven FMF patients and 10,080 age- and sex-matched controls in the Clalit Health Services medical database were identified and compared in terms of prevalence of ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionThe safety profile of adalimumab was consistent with previous findings and no new safety signals were observed.
Source: Advances in Therapy - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 15 November 2019Source: Autoimmunity ReviewsAuthor(s): José María G. Ruiz de Morales, Lluís Puig, Esteban Daudén, Juan D. Cañete, José Luis Pablos, Antonio Olveira Martín, Carlos González Juanatey, Alfredo Adán, Xavier Montalbán, Natalia Borruel, Guillermo Ortí, Esther Holgado Martín, Carolina García-Vidal, Cynthia Vizcaya Morales, Víctor Martín Vázquez, Miguel Ángel González-GayAbstractInterleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research
Conclusions: Evidence from clinical trials support that there are no differences in efficacy or safety of continuing the treatment with Infliximab BRP or exchanging into its biosimilar in patients with medical conditions approved in EsSalud. Financial analysis shows that the biosimilar introduction produce savings in purchasing institutional budget. Therefore, based on cost-opportunity principle, exchanging into biosimilar in patients receiving the original Infliximab, is a valid therapeutic alternative in the Peruvian Social Security.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Authors: El Jammal T, Gerfaud-Valentin M, Sève P, Jamilloux Y Abstract In the past ten years, the better understanding of the pathophysiological mechanisms underlying inflammatory and autoimmune diseases has led to the emergence of many targeted therapies. Among them, the Janus kinase inhibitors are acting upstream in the inflammatory cascade of several key cytokines in disorders such as rheumatoid arthritis, ulcerative colitis or psoriasis. At the moment, these three diseases represent the only indications validated by the FDA and the EMA of the use of JAK inhibitors apart from hematology. Preclinical data ...
Source: Revue de Medecine Interne - Category: Internal Medicine Tags: Rev Med Interne Source Type: research
Abstract OBJECTIVE: To compare the efficacy of secukinumab with that of placebo across the updated Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and Outcome Measures in Rheumatology (GRAPPA-OMERACT) individual PsA core domains using pooled data from 4 phase 3 psoriatic arthritis (PsA) studies and 1 phase 3 ankylosing spondylitis (AS) study. METHODS: Data were pooled from 2049 patients with PsA participating in 4 on-label phase 3 PsA studies (FUTURE 2-5), and the efficacy of each GRAPPA-OMERACT PsA core domain (musculoskeletal disease activity, skin disease activity, pain, patient glob...
Source: J Rheumatol - Category: Rheumatology Authors: Tags: J Rheumatol Source Type: research
Conclusion: This study is the largest to date analyzing the potential influence of neighborhood deprivation on ADs. Our results indicate that neighborhood deprivation may affect risk of ADs, independent of individual level sociodemographic characteristics. For health care policies, both individual and neighborhood level approaches seem to be of importance.
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
Abstract OBJECTIVE: The aim of this study was to compare patients with ankylosing spondylitis with psoriasis (ASP) and without psoriasis (AS), to axial PsA (axPsA) patients. METHODS: Two adult cohorts were recruited from the AS clinic: ASP and AS. These two cohorts were compared with two adult cohorts recruited from the PsA clinic: axPsA (radiographic sacroiliitis: ⩾bilateral grade 2 or unilateral grade 3 or 4); and Peripheral PsA. All patients were followed prospectively according to the same protocol. The demographic, clinical and radiographic variables were compared. Adjusted means were used to account f...
Source: Pain Physician - Category: Anesthesiology Authors: Tags: Rheumatology (Oxford) Source Type: research
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