Free ?-hemoglobin as biomarker for diagnosing and stratifiying severity of ?-thalassemia and other hemoglobin-related disorders

The normal development of red blood cells requires a coordinated synthesis of the hemoglobin (Hb) subunits, the ?- and ?-globins in the case of adult hemoglobin (Hb A). Unlike the ?-hemoglobin chains (?-Hb) which are soluble and form homologous tetramers, the free ?-hemoglobin chains (?-Hb) are highly instable, may form precipitates and act as active oxidants.The molecular chaperone of ?-Hb, the « Alpha-Hemoglobin Stabilizing Protein » (AHSP) was reported to specifically bind to ?-Hb to form a stable soluble heterodimer but not to the ?-Hb or to tetrameric Hb A. Hence the role of AHSP could be to prevent free ?-Hb from aggregation until the encounter of other ?, ? or ? chains. In the red blood cell of ?-thalassemic patients, AHSP acts as a scavenger against the pool of free ?-chain but may be overwhelmed by a defective production or level of availability of ?-like chains. The free ?-chain pool may thus reflect the severity of a ?-thalassemia syndrome.rnCurrently, the diagnosis of ?-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 ?-thalassemia also depends on the nature of the mutation. More generally one may need to consider the overall imbalance between the ? and ? family of globin chains. Currently, the only technique to quantify the relative excess of free ?-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. rnrnThus, the invention relates to a method for diagnosing and/or staging a hemoglobin-related disorder, such as ?-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.rnrnScientific publication(s):rnAm J Hematol., 2017 Oct, Vasseur C. et al., Elevated soluble ?-hemoglobin pool in sickle cell anemia, doi: 10.1002/ajh.24835rnBJH, 2017 Apr, Vasseur C. et al., Red blood cells free ?-hemoglobin pool: a biomarker to monitor the ?-thalassemia intermedia variability. The ALPHAPOOL StudyrnAm J Hematol., 2011 Feb, Vasseur C. et al., Evaluation of the free ?-hemoglobin pool in red blood cells: a new test providing a scale of ?-thalassemia severity, doi: 10.1002/ajh.21918

Keywords: Anemia, Thalassemia, Sickle Cell Disease, Hemoglobin-related disorders, ELISA, HTRF, Immunoassay
Patent Application number: European Procedure (Patents) (EPA) - 24 Avr. 2009 - 09 305 352.8
Inventors:
GALACTEROS FrédéricVASSEUR Corinne
Publications:
Am J Hematol. 2017 Oct;92(10):E593-E595. doi: 10.1002/ajh.24835. Epub 2017 Jul 24.Br J Haematol. 2017 Oct;179(1):142-153. doi: 10.1111/bjh.14800. Epub 2017 Jun 23.Am J Hematol. 2011 Feb;86(2):199-202. doi: 10.1002/ajh.21918.

Reference:

BIO08398-D1

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    Patent filling date: 24-04-2009
    Rare disease: No
    Second indication: No

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