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Ann Rheum Dis. 2017 Sep;76(9):1529-1536. doi: 10.1136/annrheumdis-2016-210873. Epub 2017 Mar 23.

Anticollagen type II antibodies are associated with an acute onset rheumatoid arthritis phenotype and prognosticate lower degree of inflammation during 5 years follow-up.

Author information

1
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala Sweden.
2
Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
3
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Abstract

OBJECTIVE:

Antifibrillar collagen type II (anti-CII) antibody-positive patients with rheumatoid arthritis (RA) have early but not late signs of increased inflammation and joint erosions. We wanted to replicate this in a large RA cohort, and to relate to human leukocyte antigen (HLA)-DRB1* alleles.

METHODS:

Anti-CII and anti-cyclic citrullinated peptide (CCP)2 were measured at baseline in 773 patients with RA from the Swedish Epidemiological Investigation in Rheumatoid Arthritis (EIRA) study with clinical follow-up data from the Swedish Rheumatology Quality Register (SRQ) registry, and 1476 with HLA-DRB1* information. Comparisons were done concerning C reactive protein (CRP), erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), Disease Activity Score encompassing 28 joints based on ESR (DAS28), DAS28CRP, pain-Visual Analogue Scale (VAS), global-VAS and Health Assessment Questionnaire Score (HAQ) at eight occasions during 5 years, and association with HLA-DRB1* alleles.

RESULTS:

Anti-CII associated with elevated CRP, ESR, SJC, DAS28 and DAS28CRP at diagnosis and up to 6 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 in anti-CII/anti-CCP2 double-positive patients. Anti-CII was associated with improvements in CRP, ESR, SJC, TJC and DAS28, whereas anti-CCP2 was associated with deteriorations in SJC and DAS28 over time. Anti-CII-positive patients achieved European League Against Rheumatism good or moderate response more often than negative patients. Anti-CII was positively associated with HLA-DRB1*01 and HLA-DRB1*03, with significant interaction, and double-positive individuals had >14 times higher mean anti-CII levels than HLA double negatives. Whereas smoking was associated with elevated anti-CCP2 levels, smokers had 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 anticitrullinated protein peptide autoantibodies. Although not diagnostically useful, early anti-CII determinations predict favourable inflammatory outcome in RA.

KEYWORDS:

DAS28; Outcomes research; Rheumatoid Arthritis

PMID:
28336519
PMCID:
PMC5561381
DOI:
10.1136/annrheumdis-2016-210873
[Indexed for MEDLINE]
Free PMC Article

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