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

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...

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Autores principales: Too, Chun Lai, Murad, Shahnaz, Hansson, Monika, Alm, Linda Mathsson, Dhaliwal, Jasbir Singh, Holmdahl, Rikard, Jakobsson, Per‐Johan, Alfredsson, Lars, Klareskog, Lars, Rönnelid, Johan, Padyukov, Leonid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681166/
https://www.ncbi.nlm.nih.gov/pubmed/27483449
http://dx.doi.org/10.1002/art.39827
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author Too, Chun Lai
Murad, Shahnaz
Hansson, Monika
Alm, Linda Mathsson
Dhaliwal, Jasbir Singh
Holmdahl, Rikard
Jakobsson, Per‐Johan
Alfredsson, Lars
Klareskog, Lars
Rönnelid, Johan
Padyukov, Leonid
author_facet Too, Chun Lai
Murad, Shahnaz
Hansson, Monika
Alm, Linda Mathsson
Dhaliwal, Jasbir Singh
Holmdahl, Rikard
Jakobsson, Per‐Johan
Alfredsson, Lars
Klareskog, Lars
Rönnelid, Johan
Padyukov, Leonid
author_sort Too, Chun Lai
collection PubMed
description 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 [P (corr)] = 1.06 × 10(−8)) and CitCII355–378 (17% versus 13%, P (corr) = 0.02) were significantly higher, while the frequencies of antibodies to Vim2–17 (25% versus 32%, P (corr) = 1.91 × 10(−4)), Fibβ62–81b (15% versus 30%, P (corr) = 2.47 × 10(−22)), and Eno5–21 (23% versus 50%, P (corr) = 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.
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spelling pubmed-66811662019-08-09 Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis Too, Chun Lai Murad, Shahnaz Hansson, Monika Alm, Linda Mathsson Dhaliwal, Jasbir Singh Holmdahl, Rikard Jakobsson, Per‐Johan Alfredsson, Lars Klareskog, Lars Rönnelid, Johan Padyukov, Leonid Arthritis Rheumatol Rheumatoid Arthritis 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 [P (corr)] = 1.06 × 10(−8)) and CitCII355–378 (17% versus 13%, P (corr) = 0.02) were significantly higher, while the frequencies of antibodies to Vim2–17 (25% versus 32%, P (corr) = 1.91 × 10(−4)), Fibβ62–81b (15% versus 30%, P (corr) = 2.47 × 10(−22)), and Eno5–21 (23% versus 50%, P (corr) = 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. John Wiley and Sons Inc. 2016-11-28 2017-01 /pmc/articles/PMC6681166/ /pubmed/27483449 http://dx.doi.org/10.1002/art.39827 Text en © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Rheumatoid Arthritis
Too, Chun Lai
Murad, Shahnaz
Hansson, Monika
Alm, Linda Mathsson
Dhaliwal, Jasbir Singh
Holmdahl, Rikard
Jakobsson, Per‐Johan
Alfredsson, Lars
Klareskog, Lars
Rönnelid, Johan
Padyukov, Leonid
Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title_full Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title_fullStr Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title_full_unstemmed Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title_short Differences in the Spectrum of Anti–Citrullinated Protein Antibody Fine Specificities Between Malaysian and Swedish Patients With Rheumatoid Arthritis: Implications for Disease Pathogenesis
title_sort differences in the spectrum of anti–citrullinated protein antibody fine specificities between malaysian and swedish patients with rheumatoid arthritis: implications for disease pathogenesis
topic Rheumatoid Arthritis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6681166/
https://www.ncbi.nlm.nih.gov/pubmed/27483449
http://dx.doi.org/10.1002/art.39827
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