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THU0077 Anti-collagen type ii antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation
  1. VA Manivel1,
  2. M Mullazehi1,
  3. L Padyukov2,
  4. H Westerlind3,
  5. L Klareskog2,
  6. L Alfredsson3,
  7. S Saevarsdottir2,
  8. J Rönnelid1
  1. 1Immunology genetics and Pathology, Uppsala University, Uppsala
  2. 2Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet
  3. 3Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Abstract

Background Anti-collagen II antibody (anti-CII) positive RA patients present with early but not persistent signs of inflammation and joint erosions. This early anti-CII-dependent phenotype coincides with high anti-CII levels around the time of RA diagnosis, whereafter anti-CII levels drop. Our previous studies showed that this phenotype is associated with in vitro cytokine production by monocytes, activation of granulocytes, and enhanced chemokine production by monocyte/granulocyte cocultures, stimulated with anti-CII containing immune complexes. These in vitro findings argue that elevated anti-CII levels at time of RA diagnosis are functionally related to the corresponding acute onset RA phenotype.

Objectives Our previous comparison done in a small RA cohort (n=274) describe that anti-cyclic citrullinated peptide 2 (anti-CCP2) positive patients have a severe long-term prognosis but anti-CII positive patients have transient inflammation. In the present study we wanted to extend this in a large RA cohort with clinical follow-up data, and to relate to HLA-DRB1* alleles.

Methods Anti-CII and anti-CCP2 were measured at baseline in 773 patients from the Swedish Epidemiological Investigations in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality (SRQ) registry, and 1476 patients with HLA-DRB1* information. Comparisons were done concerning CRP, ESR, TJC, SJC, DAS28, DAS28CRP, pain-VAS, global-VAS and HAQ at 8 occasions during 5 years, and association to HLA-DRB1* alleles.

Results Anti-CII was detected in 6.6% (97/1476), and anti-CCP2 in 57.9% (855/1476) of the patients. There was no significant difference in treatment strategy at diagnosis for patients with and without those antibodies. Anti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to six months, whereas anti-CCP2 associated with SJC and DAS28 from 6 months to 5 years, but not earlier. The anti-CII-associated phenotype was strong, and predominated also in anti-CII/anti-CCP2 double positive patients. Compared to baseline levels, anti-CII was asscociated with improvements in CRP, ESR, SJC, TJC and DAS28 over time, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time, compared to antibody negative patients. Anti-CII positive patients achieved EULAR good or moderate response more often than negative patients whereas the opposite was found for anti-CCP2 positive patients (figure). Anti-CII was positively associated with HLADRB1*01 and HLADRB1*03, with significant interaction, and double positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking associated with elevated anti-CCP2 levels, smokers has lower anti-CII levels.

Conclusions Anti-CII seropositive RA represents a distinct phenotype, in many respects representing the converse to the clinical, genetic and smoking associations described for ACPA. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA. The combined analysis of anti-CII and ACPA/anti-CCP2 may be a new two-dimensional tool for predicting the prognosis and chosing therapy in newly diagnosed RA patients.

Disclosure of Interest None declared

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