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Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA

1, 2, 3, 4, 5, 6, 7, 8

  1. Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
  2. Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka; Kondo Clinic for Orthopaedics and Rheumatology, Fukuoka; Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.
  3. Kondo Clinic for Orthopaedics and Rheumatology, Fukuoka, Japan.
  4. Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
  5. Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
  6. Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
  7. Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  8. Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.

CER10788 Submission on line
2018 Vol.36, N°4 - PI 0612, PF 0618
Full Papers

Rheumatology Article

 

Abstract

OBJECTIVES:
Since the presence of IgM antibodies is a hallmark of ongoing immune response, we aimed to identify immunologically active rheumatoid arthritis (RA) patients by detecting IgM anti-citrullinated protein antibody (ACPA) levels.
METHODS:
IgM ACPA levels were determined in the serum of 176 RA patients by enzyme-linked immunosorbent assay, in which parameters of reactivity against citrullinated and non-citrullinated peptides were compared to ensure the specificity. Influence of IgM rheumatoid factor (RF) on IgM ACPA detection was examined by removing IgG, using protein G-conjugated beads, or by purifying ACPA, using citrullinated peptide-conjugated beads.
RESULTS:
Although IgM specific for citrullinated proteins was detected in some patients (11%), IgM molecules reactive to both citrullinated and non-citrullinated peptides were detected in a substantial number of patient samples (12%). IgM ACPA-positive reactions were associated with the presence of IgG ACPA and IgM RF. Surprisingly, protein G-mediated removal of IgG from the serum eliminated positivity for IgM ACPA, suggesting that IgG ACPA-IgM RF complex was being detected. This assumption was confirmed by the detection of IgM RF in the eluate of protein G beads and citrullinated peptide-conjugated beads.
CONCLUSIONS:
In an attempt to detect IgM ACPA, we mostly revealed false positive reactions due to the presence of IgM molecules, which were not specific for citrullinated proteins, and IgG ACPA-IgM RF immune complex. The latter complex had been proposed to play a role in the pathogenesis of RA, and here, for the first time, we have demonstrated its presence in the sera of RA patients.

PMID: 29465353 [PubMed]

Received: 05/09/2017 - Accepted : 27/11/2017 - In Press: 14/02/2018 - Published: 19/07/2018