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The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.

The isotype and IgG subclass distribution of anti-carbamylated protein antibodies in rheumatoid arthritis patients.
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van Delft MAM, Verheul MK, Burgers LE, Derksen VFAM, van der Helm-van Mil AHM, van der Woude D, Huizinga TWJ, Toes REM, Trouw LA,


van Delft MAM, Verheul MK, Burgers LE, Derksen VFAM, van der Helm-van Mil AHM, van der Woude D, Huizinga TWJ, Toes REM, Trouw LA, (click to view)

van Delft MAM, Verheul MK, Burgers LE, Derksen VFAM, van der Helm-van Mil AHM, van der Woude D, Huizinga TWJ, Toes REM, Trouw LA,

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Arthritis research & therapy 2017 08 1519(1) 190 doi 10.1186/s13075-017-1392-z
Abstract
BACKGROUND
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. 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.

METHODS
Anti-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.

RESULTS
Anti-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.

CONCLUSIONS
In 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.

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