Journal Article

POS0046 AUTOINFLAMMATORY GENETIC VARIANTS ARE OVER-REPRESENTED IN ANKYLOSING SPONDYLITIS AND PSORIATIC ARTHRITIS COMPARED TO RHEUMATOID ARTHRITIS AND PSORIASIS

Dohey, A., Codner, D., Rahman, P., LI, Q.

2023

Overview

Ankylosing Spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory diseases of undetermined etiology. Both entities exhibit features of autoimmunity (exhibited by clonal expansion of T cell populations) and autoinflammation, as noted by the aberrant activity of innate and innate-like cells [1]. In this study, we screen for genetic variants associated with known autoinflammatory disease in patients with AS, PsA, and compare it to rheumatoid arthritis (RA) and psoriasis (Ps). The UK genome biobank identified exomes of AS, PsA, RA, and Ps patients. Autoinflammatory genes were selected from the blueprint autoinflammatory syndrome panel [2]. Twenty thousand nine hundred five missense mutations were identified from the 47 autoinflammatory genes in the blueprint panel and screened in these four cohorts. Mutational burden, mutation number, and mutation rate in these 47 genes were calculated. Exonic mutations of 1264 in AS, 886 in PsA, 5361 in RA and 5567 in Ps patients from the UK biobank were enrolled and analyzed in this study. The number of autoinflammatory variants identified was 937 in AS, 780 in PsA, 2081 in RA and 2015 in Ps. The average mutation rate in 47 genes is around 0.26 for these four diseases. The autoinflammatory panel's average mutation burden was not significantly different between these diseases (116 in AS and PsA, 118 in RA and Ps). However, when we accounted for the number of individuals screened, AS and PsA had a higher mean number of autoinflammatory variants than RA and Ps. Specifically, AS and PsA patients had a mean number of 0.741 and 0.880 variants per individual, respectively, compared to 0.388 and 0.362 for RA and Ps, respectively. This study strengths the role of autoinflammation in AS and PsA as we report an overabundance of autoinflammatory variants in AS and PsA compared to RA and psoriasis. Consideration of autoinflammatory etiology may impact current diagnostic and therapeutic approaches. [1]Mauro D, Thomas R, Guggino G, Lories R, Brown MA, Ciccia F. Ankylosing spondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. 2021 Jul;17(7):387-404. doi: 10.1038/s41584-021-00625-y. Epub 2021 Jun 10. PMID: 34113018. [2]https://blueprintgenetics.com/tests/panels/immunology/autoinflammatory-syndrome-panel/ NIL. Quan Li: None declared, Amanda Dohey: None declared, Dianne Codner: None declared, Proton Rahman Speakers bureau: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Consultant of: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis. Table 1Autoinflammatory variants in AS, PsA, RA and PsDiseaseNo. of PatientsNo. of Autoinflammatory VariantsAverage No. of Autoinflammatory Variants per patientAS12649370.741PsA8867800.880RA536120810.388Ps556720150.362

• Publisher: Elsevier B.V,Elsevier Limited
• Subject: Ankylosing spondylitis / Autoimmune diseases / Autoimmunity / Biobanks / Disease / Etiology / Genetic diversity / Genetics/Epigenetics / Genomes / Inflammatory diseases / Innate immunity / Lymphocytes T / Missense mutation / Mutation / Mutation rates / Psoriasis / Psoriatic arthritis / Rheumatoid arthritis / Spondyloarthritis