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

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.

• Authors: Xia Jiang, Leendert A Trouw, Tineke J van Wesemael, Jing Shi, Camilla Bengtsson, Henrik Källberg, Vivi Malmström, Lena Israelsson, Hulda Hreggvidsdottir, Willem Verduijn, Lars Klareskog, Lars Alfredsson, Tom W J Huizinga, Rene E M Toes, Karin Lundberg, Diane van der Woude
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 73 Issue 10 Pg. 1761-8 (Oct 2014) ISSN: 1468-2060 [Electronic] England
• PMID: 24812286 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• ANKRD1 protein, human
• Autoantibodies
• HLA-DRB1 Chains
• Immunoglobulin G
• Muscle Proteins
• Nuclear Proteins
• Peptides, Cyclic
• Repressor Proteins
• cyclic citrullinated peptide
• PTPN22 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 22

Topics

• Adolescent
• Adult
• Aged
• Alleles
• Arthritis, Rheumatoid (etiology, genetics, immunology)
• Autoantibodies (blood)
• Case-Control Studies
• Cohort Studies
• Female
• Genetic Predisposition to Disease
• Genotype
• HLA-DRB1 Chains (genetics)
• Humans
• Immunoglobulin G (blood)
• Male
• Middle Aged
• Muscle Proteins (immunology)
• Nuclear Proteins (immunology)
• Peptides, Cyclic (immunology)
• Protein Tyrosine Phosphatase, Non-Receptor Type 22 (genetics)
• Repressor Proteins (immunology)
• Risk Factors
• Smoking (adverse effects, immunology)
• Young Adult