A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient
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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.
We measured IgM-class anti-human IgG and anti-human IgA antibodies in his serum by sandwich enzyme-linked immunosorbent assay (ELISA).
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.
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.
KeywordsAID deficiency anaphylactic reaction IgM-class anti-human IgG antibody hyper-IgM syndrome
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.
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.
Compliance with Ethical Standards
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.
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