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Anticitrullinated p...
Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants.
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- Rönnelid, Johan (author)
- Uppsala universitet,Klinisk immunologi
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- Hansson, Monika (author)
- Karolinska Institutet
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- Mathsson, Linda (author)
- Uppsala universitet,Klinisk immunologi,Thermo Fisher Sci, Uppsala, Sweden
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Cornillet, Martin (author)
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Reed, Evan (author)
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- Jakobsson, Per-Johan (author)
- Karolinska Institutet
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- Alfredsson, Lars (author)
- Karolinska Institutet
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- Holmdahl, Rikard (author)
- Karolinska Institutet
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Skriner, Karl (author)
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Serre, Guy (author)
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- Lundberg, Karin (author)
- Karolinska Institutet
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- Klareskog, Lars (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-10-25
- 2018
- English.
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:2, s. 203-211
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- INTRODUCTION: The second generation anticycliccitrullinated peptide (anti-CCP2) assay detects the majority but not all anticitrullinated protein/peptide antibodies (ACPA). Anti-CCP2-positive rheumatoid arthritis (RA) is associated with HLA-DRB1* shared epitope (SE) alleles and smoking. Using a multiplex assay to detect multiple specific ACPA, we have investigated the fine specificity of individual ACPA responses and the biological impact of additional ACPA reactivity among anti-CCP2-negative patients.METHODS: We investigated 2825 patients with RA and 551 healthy controls with full data on anti-CCP2, HLA-DRB1* alleles and smoking history concerning reactivity against 16 citrullinated peptides and arginine control peptides with a multiplex array.RESULTS: The prevalence of the 16 ACPA specificities ranged from 9% to 58%. When reactivity to arginine peptides was subtracted, the mean diagnostic sensitivity increased by 3.2% with maintained 98% specificity. Of the anti-CCP2-negative patients, 16% were found to be ACPA positive. All ACPA specificities associated with SE, and all but one with smoking. Correction for arginine reactivity also conveyed a stronger association with SE for 13/16 peptides. Importantly, when all ACPA specificities were analysed together, SE and smoking associated with RA in synergy among ACPA positive, but not among ACPA-negative subjects also in the anti-CCP2-negative subset.CONCLUSIONS: Multiplexing detects an enlarged group of ACPA-positive but anti-CCP2-negative patients with genetic and environmental attributes previously assigned to anti-CCP2-positive patients. The individual correction for arginine peptide reactivity confers both higher diagnostic sensitivity and stronger association to SE than gross ACPA measurement.
Keyword
- ant-ccp
- autoantibodies
- rheumatoid arthritis
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Rönnelid, Johan
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Hansson, Monika
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Mathsson, Linda
-
Cornillet, Marti ...
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Reed, Evan
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Jakobsson, Per-J ...
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show more...
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Alfredsson, Lars
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Holmdahl, Rikard
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Skriner, Karl
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Serre, Guy
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Lundberg, Karin
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Klareskog, Lars
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show less...
- Articles in the publication
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Annals of the Rh ...
- By the university
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Uppsala University
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Karolinska Institutet