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Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis
Umea Univ, Dept Publ Hlth & Clin Med, Div Rheumatol, SE-90185 Umea, Sweden..
Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Thermo Fisher Sci, Uppsala, Sweden..
Umea Univ, Dept Stat, S-90187 Umea, Sweden..
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2016 (English)In: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, 43Article in journal (Refereed) Published
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Abstract [en]

Background: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. Methods: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. Results: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected >= 15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(580-600), filaggrin (CCP-1/Fil(307-324)) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. Conclusions: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.

Place, publisher, year, edition, pages
2016. Vol. 18, 43
Keyword [en]
Rheumatoid arthritis, Rheumatoid factor, Anti-citrullinated peptide antibodies, Pre-symptomatic individuals, Anti-carbamylated protein antibodies, Anti-CCP2 antibodies
National Category
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-280252DOI: 10.1186/s13075-016-0940-2ISI: 000370007700002PubMedID: 26860413OAI: oai:DiVA.org:uu-280252DiVA: diva2:913946
Funder
Swedish Rheumatism AssociationSwedish Research Council, K2013-52X-20307-07-3Swedish Foundation for Strategic Research
Available from: 2016-03-23 Created: 2016-03-09 Last updated: 2017-11-30Bibliographically approved

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Mathsson-Alm, LindaRönnelid, Johan

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