Abstract

IntroductionOur objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence.MethodsA total of 72 RA and 72 control sera were analyzed for binding using enzyme-linked immunosorbent assay to citrulline- or homocitrulline-containing type I and II collagen carboxyterminal telopeptides, as well as to cyclic citrullinated peptide (CCP) and to mutated citrullinated vimentin (MCV). Specificities of the antibodies were tested using inhibition-ELISA.ResultsOf the RA sera, 39 (54%) and 41 (57%) were positive for binding to CCP and MCV, respectively. Further, 34 (47%) and 30 (42%) of the patients had specific antibodies binding to and being inhibited by citrulline-containing type I collagen telopeptides and by citrulline-containing type II collagen carboxyterminal telopeptides, respectively. The corresponding figures regarding homocitrulline-containing type I and homocitrulline-containing type II collagen telopeptides were 16 (22%) and 14 (19%). Most of the patients, who were seropositive for citrullinated peptides, showed binding in multiple assays. A total of 10 (14%) RA patients were positive for all the tested peptide pairs, while 28 (39%) of them had antibodies that contained overlapping specifities between citrulline and homocitrulline in the same peptide sequence.ConclusionsAntibodies to both citrulline and homocitrulline containing type I and II collagen telopeptides can be found in sera of RA patients. These antibodies are not constant from one RA patient to another, but contain separate or overlapping specificities within the same peptide sequence varying between individuals. Our results suggest some relationship between citrulline and homocitrulline-recognizing antibodies, since homocitrulline antibodies exist mainly in individuals seropositive to anti-CCP and anti-MCV.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-014-0515-z) contains supplementary material, which is available to authorized users.

Highlights

  • Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence

  • neutrophil extracellular traps (NETs) are present in periodontitis [11] and by containing citrullinated proteins they may be involved in anti-citrullinated protein antibodies (ACPA) formation and trigger subsequent development of RA [12,13]

  • A total of 39 (54%) and 41 (57%) of the patient sera bound the respective antigens in direct enzyme-linked immunosorbent assay (ELISA) for anti-cyclic citrullinated peptide (CCP) and anti-mutated citrullinated vimentin (MCV)

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Summary

Introduction

Our objective was to find out if there are antibodies binding to homocitrulline-containing type I and II collagen carboxyterminal telopeptides in sera of patients with rheumatoid arthritis (RA), and if these antibodies cross-react with citrulline and homocitrulline in the same peptide sequence. Anti-CCP, measures the binding of the sera to a mixture of several citrullinated peptides. These peptides have been chosen to give an optimal distinction between controls and patients with RA [6]. The product of lysine carbamylation is homocitrulline, a structural homolog of citrulline. Antibodies against both citrullinated and carbamylated antigens were found to be present simultaneously in sera of RA patients [9]. NETs are present in periodontitis [11] and by containing citrullinated proteins they may be involved in ACPA formation and trigger subsequent development of RA [12,13]

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