title: The association of CD81 polymorphisms with alloimmunization in sickle cell disease.
abstract: The goal of the present work was to identify the candidate genetic markers predictive of alloimmunization in sickle cell disease (SCD). Red blood cell (RBC) transfusion is indicated for acute treatment, prevention, and abrogation of some complications of SCD. A well-known consequence of multiple RBC transfusions is alloimmunization. Given that a subset of SCD patients develop multiple RBC allo-/autoantibodies, while others do not in a similar multiple transfusional setting, we investigated a possible genetic basis for alloimmunization. Biomarker(s) which predicts (predict) susceptibility to alloimmunization could identify patients at risk before the onset of a transfusion program and thus may have important implications for clinical management. In addition, such markers could shed light on the mechanism(s) underlying alloimmunization. We genotyped 27 single nucleotide polymorphisms (SNPs) in the CD81, CHRNA10, and ARHG genes in two groups of SCD patients. One group (35) of patients developed alloantibodies, and another (40) had no alloantibodies despite having received multiple transfusions. Two SNPs in the CD81 gene, that encodes molecule involved in the signal modulation of B lymphocytes, show a strong association with alloimmunization. If confirmed in prospective studies with larger cohorts, the two SNPs identified in this retrospective study could serve as predictive biomarkers for alloimmunization.
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010-2970, USA.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Tatari-Calderone
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.forename: Gama P
authors.initials: GP
authors.lastname: Le Bouder
authors.forename: Ramita
authors.initials: R
authors.lastname: Dewan
authors.forename: Naomi L C
authors.initials: NL
authors.lastname: Luban
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lasserre
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Maury
authors.forename: François
authors.initials: F
authors.lastname: Lionnet
authors.forename: Rajagopal
authors.initials: R
authors.lastname: Krishnamoorthy
authors.forename: Robert
authors.initials: R
authors.lastname: Girot
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D017707:Erythrocyte Transfusion; D005260:Female; D015870:Gene Expression; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies; D015398:Signal Transduction; D060225:Tetraspanin 28 / Q000235:genetics* / Q000276:immunology; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: D015415:Biomarkers; C554798:CD81 protein, human; C493739:CHRNA10 protein, human; D007518:Isoantibodies; D011978:Receptors, Nicotinic; D060225:Tetraspanin 28; C075397:RHOG protein, human; D020741:rho GTP-Binding Proteins