Relative proteome quantification of alpha, beta, gamma and delta globin chains in early eluting peaks of Bio-Rad variant II ^® CE-HPLC of hemoglobin from healthy and beta-thalassemia subjects in Malaysia

Abstract

This is the first report of QQQ-mass spectrometric identification and quantification of the Hb subunits, alpha, beta, delta and gamma globin peptides, derived from enzymatic-digestion of proteins in the early unknown peaks of the Bio-Rad cation-exchange chromatography of haemoglobin. The objectives were to assess the relationship of the quantity of the free alpha, beta, delta and gamma globin chains with the phenotypic diversity of beta-thalassaemias (β-thal). The results demonstrate that the pools of free globin chains in red blood cells were correlating with the severity of the disease in patients with different phenotypes of β-thal. The mechanism and the regulation of synthesis of free globin chains pool in a normal individual and in patients with different β-thal phenotypes could arise from several mechanisms which will require further investigation. The role of the free globin pool in patients with β-thal for development of novel therapeutic approaches based on these potential targets requires further investigation. Pertinent biomarkers improves the diagnosis of the β-thal, especially in low-income countries where they are most common and allows more effective therapeutic intervention leading to more successful therapeutic outcome.

Highlights

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  Globin chains exist in the fast-eluting unknown HPLC peaks in normal human red blood cells.

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  Larger pools of globin chains in patients with β-thal are correlated with the severity of the disease.

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  Regulation and mechanisms of free globin chains pool in patients with β-thalassemias requiring further investigation.

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  Biomarker with diagnostic and prognostic utility allows more effective therapeutic outcome.