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Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA
A. Haraguchi1, H. Yamada2, M. Kondo3, K. Okazaki4, J.-I. Fukushi5, A. Oyamada6, Y. Yoshikai7, Y. Nakashima8
- Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
- 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.
- Kondo Clinic for Orthopaedics and Rheumatology, Fukuoka, Japan.
- Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
- Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
- Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
- Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
- Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan.
CER10788
2018 Vol.36, N°4
PI 0612, PF 0618
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PMID: 29465353 [PubMed]
Received: 05/09/2017
Accepted : 27/11/2017
In Press: 14/02/2018
Published: 19/07/2018
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.
