HLA-B*44 is associated with a more than twentyfold increase in cyclic citrullinated peptide antibody serum level in Croatian patients with seropositive rheumatoid arthritis

Jure Aljinović, Darko Kero, Daniela Šošo, Marin Petrić, Daniela Marasović Krstulović, Dijana Perković, Esma Čečuk-Jeličić, Sonja Jaman, Dora Dujmović and Ivanka Marinović

PLOS ONE, 2025, vol. 20, issue 12, 1-13

Abstract: Objectives: To determine whether any of the HLA-A*, HLA-B* and HLA-DR* alleles in seropositive rheumatoid arthritis (RA) can be associated with the extreme serum levels of rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (anti-CCP). Methods: This was a retrospective cross-sectional study of adult patients. Demographic data, HLA typing data and RF and anti-CCP levels were collected and analysed. Results: HLA-A*02, HLA-B*44 and HLA-DRB1*04 were more prevalent in patients from the RA cohort compared to healthy controls. Intra-cohort analysis revealed that HLA-B*44 had an increased frequency of a twenty-fold increase in anti-CCP (P = 0.033) and HLA-A*03 had a borderline (P = 0.063) frequency. HLA-A*03 was more frequent in the groups with >3-fold and >10-fold anti-CCP levels, while HLA-DRB1*04 was of borderline significance at >3-fold anti-CCP increase (P = 0.053). HLA-B*08 showed a lower frequency of 3-, 10- and 20-fold increase in anti-CCP serum levels. Carriers of B*44 (OR = 5.58; P = 0.030), DRB1*04 (OR = 3.89; P = 0.027) or A*03 (OR = 2.71; P = 0.023) were statistically significantly more likely to have a 20-fold increase in anti-CCP levels over the diagnostic threshold. None of the alleles increased the likelihood of having high or extreme RF levels. Conclusions: HLA-B*44 is associated with a twenty-fold increase in anti-CCP serum levels. HLA-A*03 and HLA-DRB1*04 have a positive trend towards a twenty-fold increase in anti-CCP levels. Earlier aggressive therapy in these patients can prevent such an extreme increase in antibody levels.

Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0334551

DOI: 10.1371/journal.pone.0334551

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