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

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 highperformance 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.