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A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient

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Abstract

Purpose

A 42-year-old man with hyper-IgM syndrome type 2 caused by activation-induced cytidine deaminase (AID) deficiency developed a severe anaphylactic reaction to intravenous immunoglobulin. The purpose of this study was to clarify the cause of the anaphylactic reaction of the patient.

Methods

We measured IgM-class anti-human IgG and anti-human IgA antibodies in his serum by sandwich enzyme-linked immunosorbent assay (ELISA).

Results

The sandwich ELISA assay revealed that serum from the patient, but not the controls, reacted to three different IgG products and purified human IgA. This indicated that the patient had IgM-class anti-human IgG and IgA antibodies in his serum, which associated with the anaphylactic reactions after the administration of IgG products. The anti-IgG antibody was likely to be the main cause of the reactions because an IgA-depleted IgG product also induced a severe reaction in this case and showed high absorbance in the ELISA system, similar to other IgG products containing more IgA.

Conclusions

This is the first report of IgM-class anti-human IgG associated with an anaphylactic reaction to an IgG infusion. The anaphylactic reactions were very severe in this case, probably because IgM-class antibodies are potent activators of the complement pathway.

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Acknowledgments

This work was supported in part by the Ministry of Defense, Japan; the Research on Measures for Intractable Diseases Project (H29-013, H26-037, H23-012): matching fund subsidy from the Ministry of Health, Labour and Welfare, Japan; the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (17913039, 26293250, 15 K09640); the Practical Research for Rare/Intractable Diseases from Japan Agency for Medical Research and Development, AMED; the Japan Foundation for Pediatric Research; the Jeffrey Modell Foundation; and the Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics.

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Authors and Affiliations

  1. Department of Pediatrics, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-0042, Japan

    Yuki Tsujita, Kohsuke Imai, Kenichi Honma, Chikako Kamae & Shigeaki Nonoyama

  2. Department of Community Pediatrics, Perinatal and Maternal Medicine, Tokyo Medical and Dental University (TMDU), Tokyo, Japan

    Kohsuke Imai

  3. Kyushu University Beppu Hospital, Beppu, Japan

    Takahiko Horiuchi

Authors
  1. Yuki Tsujita
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  2. Kohsuke Imai
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  3. Kenichi Honma
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  4. Chikako Kamae
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  5. Takahiko Horiuchi
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  6. Shigeaki Nonoyama
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Contributions

KI and SN contributed to study conception and design; YT wrote the manuscript and SN and KI reviewed the manuscript; KH performed the ELISA to detect the IgM-type anti IgG antibody; YT preformed the ELISA to detect the IgM-type anti-IgA, IgM-type anti-IgM, IgM-type anti-BSA, IgE-type anti-IgG, and IgA antibody; TH designed assays to measure C3a and C5a and YT performed those assays; KI, KH, CK, and SN contributed to interpretation of data; YT performed the statistical analysis; SN provided clinical samples and data; and all authors reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Yuki Tsujita.

Ethics declarations

The experiments in this study were done after written informed consent had been obtained and according to the permits issued by the Institutional Review Board of National Defense Medical College (permit number 1275).

Research Involving Human Participants

All procedures performed in the study were in accordance with the Helsinki principles, and the study was approved by the Institutional Review Board of the National Defense Medical College.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Electronic supplementary material

ESM 1

Detection of IgE-class anti-human IgG and anti-human IgA and IgM-class anti-IgM in the serum by sandwich ELISA. Data indicate spectrophotometric absorption at 450 nm. Data shown in the figures are the mean ± standard error obtained in one experiment performed in doublet. A IgE-class anti-human IgG was measured using IgG products as coating antibody. B IgE-class anti-human IgA was measured using purified human IgA as the coating antibody. C IgM-class anti-human IgM was measured using purified human IgM as the coating antibody. D IgM-class anti-bovine serum albumin was measured using bovine serum albumin (BSA) as coating protein to exclude the presence of nonspecific IgM-class antibody. (PDF 106 kb)

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Tsujita, Y., Imai, K., Honma, K. et al. A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient. J Clin Immunol 38, 144–148 (2018). https://doi.org/10.1007/s10875-017-0466-7

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  • DOI: https://doi.org/10.1007/s10875-017-0466-7

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