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A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis
Rheumatology Clinic, Falun Hospital, Falun.
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
Spenshult Rheumatology Centre, Oskarström, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
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2011 (English)In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 7, 1265-1272 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

Place, publisher, year, edition, pages
Journal of Rheumatology , 2011. Vol. 38, no 7, 1265-1272 p.
Keyword [en]
ANTICYCLIC CITRULLINATED PEPTIDE ANTIBODIES, VIMENTIN, EARLY ARTHRITIS, RHEUMATOID ARTHRITIS, IgA
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-70512DOI: 10.3899/jrheum.101086ISI: 000293041600009OAI: oai:DiVA.org:liu-70512DiVA: diva2:440120
Note

Funding Agencies|Center for Clinical Research in Dalarna||Swedish Research Council||Swedish Society Against Rheumatism||Gustaf Vth 80-year Foundation||Karin Svensson, Siv Olsson||Gunnar Trosell Foundations for rheumatology research||Reinhold Sund Foundation||Tore Nilson Foundation||Abbott||

Available from: 2011-09-12 Created: 2011-09-12 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis
Open this publication in new window or tab >>Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation and subsequent destruction of cartilage and bone. The etiology is largely unknown, although genetic as well as environmental factors are involved. The manifestations and consequences of RA differ between individuals. This makes it important to find early markers for the disease course, in order to enable the most suitable treatment. IgG antibodies to cyclic citrullinated peptides (CCP) have high specificity for RA, but only around 60% of RA patients test positive for IgG anti-CCP.

The aim of this thesis was to evaluate the usefulness of serum IgA anti-CCP as a diagnostic maker compared to IgG anti-CCP, and to assess IgA versus IgG anti-CCP status in relation to smoking habits and genetic background. Another aim was to evaluate signs of mucosal immunization by analyzing salivary IgA anti-CCP.

IgA anti-CCP was present in a subgroup of RA patients with high levels of IgG anti-CCP and a slightly more severe disease course. Similar results were found regarding IgA class antibodies to modified citrullinated vimentin (MCV). IgG anti-MCV had slightly higher sensitivity for RA than IgG anti-CCP, thus identifying a group of IgG anti-CCP negative patients with an unfavourable disease course. However, the lower diagnostic specificity of IgG anti-MCV limits its usefulness.

Among 63 patients with established RA, salivary IgA anti-CCP was found in 22% and was associated with a more favourable outcome regarding erosive joint disease at follow-up. IgA anti-CCP in serum was strongly associated with smoking, and the earlier known interaction between smoking and shared epitope (SE) was here shown to be valid only for subjects positive for IgA anti-CCP in combination with IgG anti-CCP.

In conclusion, IgG anti-CCP is still the most useful serologic marker of RA, but IgA anti-CCP should be further investigated as a prognostic marker. The association between smoking and IgA anti-CCP strongly indicates a pathogenic role for smoking and IgA anti-CCP, supporting the possibility that RA may originate from chronic airway irritation. The less erosive disease in patients positive for salivary IgA anti-CCP indicates a protective role of secretory IgA anti-CCP.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 78 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1404
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-105987 (URN)10.3384/diss.diva-105987 (DOI)978-91-7519-342-7 (ISBN)
Public defence
2014-05-15, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
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Available from: 2014-04-15 Created: 2014-04-15 Last updated: 2015-08-31Bibliographically approved

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Kastbom, AlfReckner-Olsson, ÅsaSkogh, Thomas

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