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Ann Rheum Dis. 2014 Oct;73(10):1761-8. doi: 10.1136/annrheumdis-2013-205109. Epub 2014 May 8.

Anti-CarP antibodies in two large cohorts of patients with rheumatoid arthritis and their relationship to genetic risk factors, cigarette smoking and other autoantibodies.

Author information

1
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
2
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
3
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
4
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
5
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Center for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.

Abstract

INTRODUCTION:

In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. In this study, we have analysed the relationships among anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA.

METHODS:

Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by inhouse ELISAs among RA cases in the Leiden Early Arthritis Clinic (n=846) and in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (n=1985) cohorts. ORs for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in meta-analysis in RA subsets defined by the presence/absence of anti-CarP and anticyclic citrullinated peptide (anti-CCP) antibodies.

RESULTS:

In both cohorts, anti-CarP antibody positivity was mainly detected in the anti-CCP-positive population (49%-73%), but also in the anti-CCP-negative population (8%-14%). No associations between anti-CarP antibodies and HLA-DRB1 shared epitope alleles could be identified, while there were data to support an association between anti-CarP-FCS and HLA-DRB1*03. Further analyses did not reveal any specific associations of anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes or smoking.

CONCLUSIONS:

Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. There were no significant associations among anti-CarP antibodies and HLA-DRB1 alleles, PTPN22 or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation.

KEYWORDS:

Autoantibodies; Epidemiology; Gene Polymorphism; Rheumatoid Arthritis

Comment in

PMID:
24812286
DOI:
10.1136/annrheumdis-2013-205109
[Indexed for MEDLINE]
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