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Alloimmunization risk associated with amino acid 223 substitution in the RhD protein: analysis in the light of molecular modeling.
de Brevern, Alexandre G; Floch, Aline; Barrault, Aurélie; Martret, Jennifer; Bodivit, Gwellaouen; Djoudi, Rachid; Pirenne, France; Tournamille, Christophe.
Afiliación
  • de Brevern AG; INSERM UMR_S 1134, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. Antilles, Paris.
  • Floch A; Laboratory of Excellence GR-Ex, Paris.
  • Barrault A; Institut National de la Transfusion Sanguine (INTS), Paris.
  • Martret J; Laboratory of Excellence GR-Ex, Paris.
  • Bodivit G; Etablissement Français du Sang Ile de France, Créteil, France.
  • Djoudi R; IMRB-INSERM U955 Team 2 "Transfusion et Maladies du Globule Rouge", Créteil, France.
  • Pirenne F; UPEC, Université Paris Est-Créteil, Créteil, France.
  • Tournamille C; Etablissement Français du Sang Ile de France, Créteil, France.
Transfusion ; 58(11): 2683-2692, 2018 11.
Article en En | MEDLINE | ID: mdl-30284289
BACKGROUND: Partial D status is a major concern for transfusion and pregnancy, due to the possibility of carriers becoming immunized. When known carriers of a D variant have never been exposed to complete D, they are assumed to have D partial status based on the position of the amino acid substituted. New approaches for predicting immunization risk are required. We built a three-dimensional (3D) structural model to investigate the consequences of substitutions of Amino Acid 223 involved in a large number of D variants. STUDY DESIGN AND METHODS: Homology modeling was performed with multiple templates. The model was evaluated by comparing the interactions of the known p.Phe223Val variant (RHD*08.01) and a new p.Phe223Ser variant (RHD*52) to RhD reference allele (p.Phe223). The consequences predicted by modeling the variants were compared with serologic data. RESULTS: The 3D structural model was generated from two related protein structures and assessed with state-of-the-art approaches. An analysis of the interactions of the variant Residue 223 in the proposed 3D model highlighted the importance of this position. Modeling predictions were consistent with the serologic and clinical data obtained for the D antigen with a substitution of Amino Acid 223. CONCLUSION: We used a 3D structural model to evaluate the effect of the p.Phe223 substitution on the conformation of the RhD protein. This model shed light on the influence of substitutions on the structure of the RhD protein and the associated alloimmunization risk. These initial findings indicate that the p.Phe223Ser variant can be considered partial.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Globulina Inmune rho(D) / Sustitución de Aminoácidos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transfusion Año: 2018 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Globulina Inmune rho(D) / Sustitución de Aminoácidos Tipo de estudio: Etiology_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Transfusion Año: 2018 Tipo del documento: Article