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A case of variant hemoglobin (Hb Agenogi) with type 2 diabetes mellitus showed high HbA1c levels measured by immunoassay due to enhanced antigenicity

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Abstract

HbA1c is a widely utilized biomarker for the management of diabetes mellitus. The presence of variant hemoglobins might interfere with HbA1c measurement using different methods. We herein describe Hb Agenogi (β90Glu → Lys) with type 2 diabetes mellitus whose HbA1c measured by immunoassay (IA) showed falsely high levels while HbA1c measured by high-performance liquid chromatography (HPLC) in the standard mode (SM) showed falsely low levels. To clarify the cause of the falsely high-IA-HbA1c levels, HbA1c was measured by various methods. Glycated albumin was slightly higher than the reference range. HbA1c measured by HPLC in the variant mode, affinity assay and enzymatic assay showed the range (mean ± 2SD: 6.0–6.8%) in this case. However, HbA1c measured by several HPLC-SMs showed falsely low levels (4.1–4.4%). IA-HbA1c using an antibody manufactured by Fujirebio Inc. showed falsely high levels (7.3–8.2%); whereas, IA-HbA1c using an antibody manufactured by Roche Ltd. showed the expected range (6.2–6.5%). In the case of Hb Agenogi, IA-HbA1c using an antibody manufactured by Fujirebio yielded falsely high levels. The mutation at codon 90 of the β-globin chain might enhance antigenicity of the N-terminal peptide region and, therefore, lead to falsely high-HbA1c levels in IA-HbA1c.

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Acknowledgements

The authors would like to acknowledge the following institutions for their assistance in performing HbA1c measurements in this case of Hb Agenogi: Arkray Inc., Tosoh Co., Sekisui Medical Co., Bio-Rad Laboratories, Inc., Kyowa Medex Co., Fujirebio Inc., Nihon Kohden Co., Roche Diagnostics K.K., and Ortho Clinical Diagnostics Inc.

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Authors and Affiliations

  1. Department of Internal Medicine, Yamane Hospital, Hamada, Shimane, Japan

    Yuko Yamane & Michihiro Tsumori

  2. Department of Laboratory Medicine, New Tokyo Hospital, Matsudo, Chiba, Japan

    Midori Ishibashi

  3. Department of Internal Medicine, Hakuhokai Central Hospital, 4-23-1 Higashisonodacho, Amagasaki, Hyogo, 661-0953, Japan

    Masafumi Koga

Authors
  1. Yuko Yamane
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  2. Michihiro Tsumori
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  3. Midori Ishibashi
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  4. Masafumi Koga
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Correspondence to Masafumi Koga.

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The authors declare that they have no conflict of interest.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients prior to their participation in this study.

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Yamane, Y., Tsumori, M., Ishibashi, M. et al. A case of variant hemoglobin (Hb Agenogi) with type 2 diabetes mellitus showed high HbA1c levels measured by immunoassay due to enhanced antigenicity. Diabetol Int 10, 138–142 (2019). https://doi.org/10.1007/s13340-018-0383-x

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  • DOI: https://doi.org/10.1007/s13340-018-0383-x

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