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Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
Euro-Diagnostica AB, Malmö, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.ORCID iD: 0000-0002-0153-9249
2013 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 218, no 2, 232-237 p.Article in journal (Refereed) Published
Abstract [en]

Circulating IgG anti-cyclic citrullinated peptide antibodies (CCP) are highly specific for rheumatoid arthritis (RA) and prognostic of poor outcome. Serum IgA anti-CCP occurs in a subset of IgG-positive cases and relates to still more aggressive disease. Mucosal IgA-class antibodies, however, are generally associated with anti-inflammatory actions and systemic tolerance induction. In the present study, unstimulated salivary samples from 63 patients with established RA and 20 healthy persons were analysed by enzyme-linked immunoassay for the presence of IgA anti-CCP antibodies. To ensure antigen specificity, IgA-reactivity with the corresponding uncitrullinated antigen, cyclic arginine peptide (CAP), was analysed and anti-CCP/anti-CAP ratios calculated. Retrospective data regarding disease activity and radiological outcome were achieved via medical records. Salivary IgA anti-CCP was found in 14/63 (22%) patients and one (5%) control (positive test = anti-CCP/anti-CAP ratio andgt; 1.5). Salivary IgA reactivity was dose-dependently inhibited by pre-incubation with soluble CCP to a degree strongly correlating with anti-CCP/anti-CAP ratio. In salivary IgA anti-CCP positive patients, joint erosions within 6 years of diagnosis was significantly lower (p = 0.043), and at the time for diagnosis there was a trend towards lower erythrocyte sedimentation rate (p = 0.071) and C-reactive protein (p = 0.085). Contrasting to circulating IgG and IgA anti-CCP, our results imply that salivary IgA antibodies may be associated with a less severe outcome of RA. Hypothetically, this relates to an anti-inflammatory and protective immunomodulating role of secretory IgA-class autoantibodies against citrullinated antigens presented at mucosal surfaces.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 218, no 2, 232-237 p.
Keyword [en]
Citrullinated peptides, IgA, Rheumatoid arthritis, Saliva, Mucosal immunity
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-90205DOI: 10.1016/j.imbio.2012.04.011ISI: 000315312000013OAI: oai:DiVA.org:liu-90205DiVA: diva2:612354
Note

Funding Agencies|Centre for Clinical Research in Dalarna||Swedish Research Council|2008-2832|Swedish Association Against Rheumatism||King Gustaf Vth 80-Year Foundation||County Council of Ostergotland Research Foundations||Medical Research County Council of South-East Sweden (FORSS)||

Available from: 2013-03-21 Created: 2013-03-21 Last updated: 2017-12-06
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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