Differences in the Spectrum of Anti-Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis.

Abstract

OBJECTIVE:

Antibodies to the citrullinated protein antigens (ACPAs) are important in the diagnosis and pathogenesis of rheumatoid arthritis (RA). However, the prevalence of ACPAs with different fine specificities in different populations is unclear. This study sought to examine the fine specificity of the antibody responses toward citrullinated proteins in RA patients from Malaysia, an area where genetic and environmental determinants of RA are different from those in more frequently studied cohorts of Caucasian subjects.

METHODS:

A multiplex analytic microarray system was used to analyze the occurrence of antibodies to 10 different citrullinated peptides (filaggrin [fil307-324], vimentin [Vim2-17, Vim60-75], fibrinogen [Fibα563-583, Fibα580-600, Fibβ36-52, Fibβ62-81a, Fibβ62-81b], enolase [Eno5-21], and type II collagen [CitCII355-378]) in serum samples from 4,089 RA patients (1,231 Malaysian and 2,858 Swedish) and 827 healthy control subjects (249 Malaysian and 578 Swedish). The positive reaction threshold for each peptide was set separately for each population based on a specificity of 98%.

RESULTS:

Distinct differences in the frequencies of 5 ACPA fine specificities (Vim60-75, Vim2-17, Fibβ62-81b, Eno5-21, and CitCII355-378) were found between the Malaysian and Swedish RA populations, despite a nearly identical percentage of patients in each population who were positive for anti-cyclic citrullinated peptide 2 antibodies. In Malaysian RA patients compared with Swedish RA patients, the frequencies of antibodies to Vim60-75 (54% versus 44%, corrected P [Pcorr ] = 1.06 × 10-8 ) and CitCII355-378 (17% versus 13%, Pcorr  = 0.02) were significantly higher, while the frequencies of antibodies to Vim2-17 (25% versus 32%, Pcorr  = 1.91 × 10-4 ), Fibβ62-81b (15% versus 30%, Pcorr  = 2.47 × 10-22 ), and Eno5-21 (23% versus 50%, Pcorr  = 3.64 × 10-57 ) were significantly lower.

CONCLUSION:

Serum ACPA fine specificities differ between RA patients in different populations, although the total proportions of individuals positive for ACPAs are similar. Differing patterns of ACPA fine specificity could be attributed to variations in genetic and/or environmental factors.

• Authors: Chun Lai Too, Shahnaz Murad, Monika Hansson, Linda Mathsson Alm, Jasbir Singh Dhaliwal, Rikard Holmdahl, Per-Johan Jakobsson, Lars Alfredsson, Lars Klareskog, Johan Rönnelid, Leonid Padyukov
• Journal: Arthritis & rheumatology (Hoboken, N.J.) (Arthritis Rheumatol) Vol. 69 Issue 1 Pg. 58-69 (01 2017) ISSN: 2326-5205 [Electronic] United States
• PMID: 27483449 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Chemical References

• Autoantibodies
• FLG protein, human
• Filaggrin Proteins
• Peptides, Cyclic
• cyclic citrullinated peptide

Topics

• Adolescent
• Adult
• Aged
• Antibody Specificity
• Arthritis, Rheumatoid (immunology)
• Autoantibodies (immunology)
• Case-Control Studies
• Female
• Filaggrin Proteins
• Humans
• Malaysia
• Male
• Middle Aged
• Peptides, Cyclic (immunology)
• Sweden
• Young Adult