liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Salivary IgA antibodies to cyclic citrullinated peptides (CCP) in rheumatoid arthritis
Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
Euro-Diagnostica AB, Malmö, Sweden.
Linköpings universitet, Institutionen för klinisk och experimentell medicin, Reumatologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.ORCID-id: 0000-0002-0153-9249
2013 (Engelska)Ingår i: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 218, nr 2, s. 232-237Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2013. Vol. 218, nr 2, s. 232-237
Nyckelord [en]
Citrullinated peptides, IgA, Rheumatoid arthritis, Saliva, Mucosal immunity
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-90205DOI: 10.1016/j.imbio.2012.04.011ISI: 000315312000013OAI: oai:DiVA.org:liu-90205DiVA, id: diva2:612354
Anmärkning

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)||

Tillgänglig från: 2013-03-21 Skapad: 2013-03-21 Senast uppdaterad: 2017-12-06
Ingår i avhandling
1. Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis
Öppna denna publikation i ny flik eller fönster >>Circulating and Mucosal Antibodies to Citrullinated Antigens in Rheumatoid Arthritis
2014 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2014. s. 78
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1404
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-105987 (URN)10.3384/diss.diva-105987 (DOI)978-91-7519-342-7 (ISBN)
Disputation
2014-05-15, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2014-04-15 Skapad: 2014-04-15 Senast uppdaterad: 2019-11-19Bibliografiskt granskad

Open Access i DiVA

fulltext(391 kB)1215 nedladdningar
Filinformation
Filnamn FULLTEXT03.pdfFilstorlek 391 kBChecksumma SHA-512
cd82fc57b0e13d8cde37b52facbc4e6c58247fd2a89dab41d3121f184218b91439a3ee8069c765cf04f1fdf2e8ef6326151022612113bb8e4a8b6a95cf13cf9f
Typ fulltextMimetyp application/pdf

Övriga länkar

Förlagets fulltext

Personposter BETA

Svärd, AnnaKastbom, AlfSkogh, Thomas

Sök vidare i DiVA

Av författaren/redaktören
Svärd, AnnaKastbom, AlfSkogh, Thomas
Av organisationen
Institutionen för klinisk och experimentell medicinHälsouniversitetetReumatologiReumatologiska kliniken i Östergötland
I samma tidskrift
Immunobiology
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 1217 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

doi
urn-nbn

Altmetricpoäng

doi
urn-nbn
Totalt: 202 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf