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

Akihisa Haraguchi, Hisakata Yamada, Masakazu Kondo, Ken Okazaki, Jun-Ichi Fukushi, Akiko Oyamada, Yasunobu Yoshikai, Yasuharu Nakashima

Research output: Contribution to journalArticle

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Abstract

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.

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.

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.

Original languageEnglish
Pages (from-to)612-618
Number of pages7
JournalClinical and experimental rheumatology
Volume36
Issue number4
Publication statusPublished - Jul 1 2018

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Rheumatoid Factor
Antigen-Antibody Complex
Immunoglobulin M
Rheumatoid Arthritis
Antibodies
Serum
Proteins
Peptides
anti-IgG
anti-IgM
Immunoglobulin G
False Positive Reactions

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA. / Haraguchi, Akihisa; Yamada, Hisakata; Kondo, Masakazu; Okazaki, Ken; Fukushi, Jun-Ichi; Oyamada, Akiko; Yoshikai, Yasunobu; Nakashima, Yasuharu.

In: Clinical and experimental rheumatology, Vol. 36, No. 4, 01.07.2018, p. 612-618.

Research output: Contribution to journalArticle

Haraguchi, A, Yamada, H, Kondo, M, Okazaki, K, Fukushi, J-I, Oyamada, A, Yoshikai, Y & Nakashima, Y 2018, 'Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA', Clinical and experimental rheumatology, vol. 36, no. 4, pp. 612-618.
Haraguchi A, Yamada H, Kondo M, Okazaki K, Fukushi J-I, Oyamada A et al. Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA. Clinical and experimental rheumatology. 2018 Jul 1;36(4):612-618.
Haraguchi, Akihisa ; Yamada, Hisakata ; Kondo, Masakazu ; Okazaki, Ken ; Fukushi, Jun-Ichi ; Oyamada, Akiko ; Yoshikai, Yasunobu ; Nakashima, Yasuharu. / Serum IgG ACPA-IgM RF immune complexes were detected in rheumatoid arthritis patients positive for IgM ACPA. In: Clinical and experimental rheumatology. 2018 ; Vol. 36, No. 4. pp. 612-618.
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abstract = "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.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.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.",
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AU - Haraguchi, Akihisa

AU - Yamada, Hisakata

AU - Kondo, Masakazu

AU - Okazaki, Ken

AU - Fukushi, Jun-Ichi

AU - Oyamada, Akiko

AU - Yoshikai, Yasunobu

AU - Nakashima, Yasuharu

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N2 - 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.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.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.

AB - 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.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.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.

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