Abstract
BackgroundAnti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. At present, the breadth and molecular make-up of the anti-CarP antibody response is ill defined. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients.MethodsAnti-CarP antibody IgM, IgA, and IgG or IgG subclasses were detected by enzyme-linked immunosorbent assay (ELISA) in sera from 373 unselected RA patients and 196 healthy controls. An additional 114 anti-citrullinated protein antibody (ACPA) and anti-CarP IgG double-positive patients were selected to study the concomitant presence of both antibody systems.ResultsAnti-CarP IgG was present in around 45% of the patients and comprised all anti-CarP IgG subclasses. The presence of anti-CarP IgG1 particularly associates with radiological damage. Anti-CarP IgM was detected in 16% of RA patients, even in anti-CarP IgG-positive individuals, and is indicative of an actively ongoing immune response. Around 45% of the patients were positive for IgA which included ACPA-positive cases but also 24% of the ACPA-negative cases. In ACPA and anti-CarP double-positive patients, the distribution and number of isotypes and IgG subclasses was similar for both autoantibodies at the group level, but substantial variation was observed within individual patient samples.ConclusionsIn RA, the anti-CarP antibody response uses a broad spectrum of isotypes and seems to be an actively ongoing immune reaction. Furthermore, the anti-CarP and ACPA autoantibody responses seems to be differentially regulated.
Highlights
Anti-carbamylated protein antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties
The anti-CarP antibody response uses a wide spectrum of isotypes and IgG subclasses Anti-CarP antibody isotypes and IgG subclasses were measured in baseline serum samples of RA patients (n = 373) and in serum samples of healthy controls (n = 196)
At this cut-off we observed that 16.4% of the RA patients were positive for IgM anti-CarP antibodies, while 49.2% and 40.8% were positive for IgG and IgA (Fig. 1a)
Summary
Anti-carbamylated protein (anti-CarP) antibodies have recently been reported to occur in around 45% of rheumatoid arthritis (RA) patients and to have prognostic and diagnostic properties. To understand the anti-CarP antibody immune response and potential immune effector mechanisms it can recruit, we determined the anti-CarP antibody isotype and IgG-subclass usage in RA patients. Rheumatoid arthritis (RA) is a systemic autoimmune disease principally affecting synovial joints [1, 2]. Autoantibodies can be detected in the serum and synovial fluid (SF) of RA patients and may form immune complexes in the joints, leading to the attraction of immune cells through, for example, complement activation [3, 4] which can contribute to chronic inflammation and bone destruction. Anti-carbamylated protein (anti-CarP) antibodies, which target carbamylated proteins, have been detected in RA [6]. Carbamylation is a post-translational modification of proteins in which lysines are converted to homocitrullines by a chemical reaction with cyanate [7, 8]
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