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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1519159
This article is part of the Research Topic Novel Biomarkers for Early Diagnosis, involved in Autoimmune and Autoinflammatory Diseases View all 4 articles

Association of ERAP1 and ERAP2 gene polymorphisms and ERAP2 protein with the susceptibility and severity of rheumatoid arthritis in the Ukrainian population

Provisionally accepted
Iryna Kril Iryna Kril 1,2Andrzej Wiśniewski Andrzej Wiśniewski 2Agnieszka Tarnowska Agnieszka Tarnowska 2Khrystyna Lishchuk-Yakymovych Khrystyna Lishchuk-Yakymovych 1Yaryna Bojko Yaryna Bojko 1Piotr Kusnierczyk Piotr Kusnierczyk 2Valentyna V Chopyak Valentyna V Chopyak 1Izabela Nowak Izabela Nowak 2*
  • 1 Department of Clinical Immunology and Allergology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
  • 2 Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

The final, formatted version of the article will be published soon.

    Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. Although RA is chiefly associated with HLA class II, nevertheless some HLA class I associations have also been observed. These molecules present antigenic peptides to CD8+ T lymphocytes and natural killer cells. HLA-I molecules bind their peptide cargo (8–10 amino acids long) in the endoplasmic reticulum. Peptides longer than 10 amino acids are trimmed by the endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 to fit the peptide binding groove of the HLA-I molecule. Here, we investigated the possible association of ERAP1 and ERAP2 polymorphisms with RA, and also any possible correlation between serum levels of the ERAP2 protein with disease severity. We found significant associations of ERAP1 rs30187, rs27044, and rs26618, as well as ERAP2 rs2248374, with susceptibility to RA. ERAP1 rs26653 and ERAP2 rs2248374 were also associated with the Disease Activity Score (DAS28), and some polymorphisms were also associated with anti-citrullinated protein or anti-mutated citrullinated vimentin antibodies. RA patients secreted higher concentrations of ERAP2 than controls. Patients with mild disease activity (DAS28 < 3.2) released a concentration of ERAP2 four times lower than that of patients with severe disease activity (DAS28 > 5.1). We detected a higher level of ERAP2 in rheumatoid factor (RF)-positive patients than in RF-negative patients. ERAP2 concentration above 5.85 ng/mL indicated a severe phase of RA. In conclusion, some ERAP1 and ERAP2 polymorphisms seem to be related to susceptibility to RA or the severity of the disease. The ERAP2 protein tested in serum could be a valuable biomarker of RA severity.

    Keywords: Rheumatoid arthritis, MHC I class, ERAP1, ERAP2, Single nucleotide polymorphisms

    Received: 29 Oct 2024; Accepted: 30 Dec 2024.

    Copyright: © 2024 Kril, Wiśniewski, Tarnowska, Lishchuk-Yakymovych, Bojko, Kusnierczyk, Chopyak and Nowak. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Izabela Nowak, Department of Clinical Immunology, Laboratory of Immunogenetics and Tissue Immunology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland

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