The normal development of red blood cells requires a coordinated synthesis of the hemoglobin (Hb) subunits, the α- and β-globins in the case of adult hemoglobin (Hb A). Unlike the β-hemoglobin chains (β-Hb) which are soluble and form homologous tetramers, the free α-hemoglobin chains (α-Hb) are highly instable, may form precipitates and act as active oxidants.The molecular chaperone of α-Hb, the « Alpha-Hemoglobin Stabilizing Protein » (AHSP) was reported to specifically bind to α-Hb to form a stable soluble heterodimer but not to the β-Hb or to tetrameric Hb A. Hence the role of AHSP could be to prevent free α-Hb from aggregation until the encounter of other β, δ or γ chains. In the red blood cell of β-thalassemic patients, AHSP acts as a scavenger against the pool of free α-chain but may be overwhelmed by a defective production or level of availability of β-like chains. The free α-chain pool may thus reflect the severity of a β-thalassemia syndrome.
Currently, the diagnosis of β-thalassemia is still based on the hematological parameters of the patients and the molecular diagnosis is obtained by PCR techniques to identify point mutations for most at-risk populations. The severity of the β-thalassemia also depends on the nature of the mutation. More generally one may need to consider the overall imbalance between the α and β family of globin chains. Currently, the only technique to quantify the relative excess of free α-Hb is to carry out globin biosynthesis in vitro in the presence of a radioactive amino-acid. Therefore, there is a need for a method for easily diagnosing and/or staging a hemoglobin-related disorder without using molecular or radioactive technique.
Thus, the invention relates to a method for diagnosing and/or staging a hemoglobin-related disorder, such as β-thalassemias, in a subject in need thereof. The invention also relates a method for monitoring a treatment against said hemoglobin-related disorder in a subject in need thereof.
Scientific publication(s):
Am J Hematol., 2017 Oct, Vasseur C. et al., Elevated soluble α-hemoglobin pool in sickle cell anemia, doi: 10.1002/ajh.24835
BJH, 2017 Apr, Vasseur C. et al., Red blood cells free α-hemoglobin pool: a biomarker to monitor the β-thalassemia intermedia variability. The ALPHAPOOL Study
Am J Hematol., 2011 Feb, Vasseur C. et al., Evaluation of the free α-hemoglobin pool in red blood cells: a new test providing a scale of β-thalassemia severity, doi: 10.1002/ajh.21918