Potential of MALDI-TOF mass spectrometry to overcome the interference of hemoglobin variants on HbA1c measurement.

Abstract

Hemoglobin (Hb) variants remain an important cause of erroneous HbA1c results. We present an approach to overcome the interference of Hb variants on HbA1c measurements using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Samples containing or not containing Hb variants were analyzed for HbA1c using an MALDI-TOF MS system (QuanTOF) and a boronate affinity comparative method (Ultra2). For QuanTOF, two sets of HbA1c values were obtained through α- and β-chain glycation. A robust correlation between the glycation degrees of the α- and β-chains was found, and HbA1c values derived from α- and β-chain glycation correlated well with the Ultra2 results. Statistically significant differences (p<0.01) were found for all the Hb variants tested. When using the conventional β-chain glycation to determine HbA1c, clinically significant differences were only found among samples containing β-chain variants detected by QuanTOF (i.e., Hb J-Bangkok, Hb G-Coushatta, and Hb G-Taipei). In contrast, based on α-chain glycation, no clinically significant differences were found for these three variants. In addition to conventional β-chain glycation, α-chain glycation can be used to calculate HbA1c values. The interference of Hb variants on HbA1c quantification can be overcome by employing the glycation of the globin chain without a genetic variant to estimate HbA1c values.