title: Variant RH alleles and Rh immunisation in patients with sickle cell disease.
abstract: BACKGROUND
  Alloimmunisation is a major complication in patients with sickle cell disease (SCD) receiving red blood cell (RBC) transfusions and despite provision of Rh phenotyped RBC units, Rh antibodies still occur. These antibodies in patients positive for the corresponding Rh antigen are considered autoantibodies in many cases but variant RH alleles found in SCD patients can also contribute to Rh alloimmunisation. In this study, we characterised variant RH alleles in 31 SCD patients who made antibodies to Rh antigens despite antigen-positive status and evaluated the clinical significance of the antibodies produced.
  
  
  METHODS
  RHD and RHCE BeadChip™ from BioArray Solutions and/or amplification and sequencing of exons were used to identify the RH variants. The serological features of all Rh antibodies in antigen-positive patients were analysed and the clinical significance of the antibodies was evaluated by retrospective analysis of the haemoglobin (Hb) levels before and after transfusion; the change from baseline pre-transfusion Hb and the percentage of HbS were also determined.
  
  
  RESULTS
  We identified variant RH alleles in 31/48 (65%) of SCD patients with Rh antibodies. Molecular analyses revealed the presence of partial RHD alleles and variant RHCE alleles associated with altered C and e antigens. Five patients were compound heterozygotes for RHD and RHCE variants. Retrospective analysis showed that 42% of antibodies produced by the patients with RH variants were involved in delayed haemolytic transfusion reactions or decreased survival of transfused RBC.
  
  
  CONCLUSIONS
  In this study, we found that Rh antibodies in SCD patients with RH variants can be clinically significant and, therefore, matching patients based on RH variants should be considered.
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Emilia
authors: E
authors: Sippert
authors: Fujisan, Fortaleza, Brazil.
authors: Claudia R
authors: CR
authors: Fujita
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Debora
authors: D
authors: Machado
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Glaucia
authors: G
authors: Guelsin
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Ane C
authors: AC
authors: Gaspardi
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Jordão
authors: J
authors: Pellegrino
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Simone
authors: S
authors: Gilli
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Sara S T O
authors: SS
authors: Saad
authors: National Institute of Science and Blood Technology, Campinas Centre Blood, UNICAMP, Campinas, Brazil.
authors: Lilian
authors: L
authors: Castilho
mesh_terms: D000483:Alleles; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000628:therapy; D001788:Blood Grouping and Crossmatching; D017707:Erythrocyte Transfusion; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000097:blood* / Q000276:immunology; D008297:Male; D012204:Rh-Hr Blood-Group System / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D007518:Isoantibodies; C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen