title: HLA-DRB1 polymorphism is associated with Kell immunisation.
abstract: K immunisation is observed in some polytransfused patients and pregnant women but does not occur in all cases of K incompatibility. This study analysed the role of genetic background in this selective response to K antigen by investigating HLA-DRB1 alleles associated with K immunisation in a southern European population. HLA-DRB1 genotyping was performed by polymerase chain reaction sequence-specific oligonucleotide/sequence-specific primer procedures in 54 K immunised patients and 200 healthy controls. The frequency of HLA-DRB1*11 was significantly higher in K immunised patients than healthy controls: 31 of 54 (57%) vs. 56 of 200 (28%) (P(c) < 0.001). In the remaining K immunised HLA-DRB1*11-negative patients, the frequency of HLA-DRB1*13 was increased: 14 of 23 (61%) vs. 49 of 144 in healthy controls (34%) (P < 0.02). The combined frequency of the two HLA-DRB1 alleles (HLA-DRB1*11 and HLA-DRB1*13) was 83% in K immunised patients when compared with 52% in healthy controls (P(c) < 0.001). K and k differ by a single amino acid T193 (M). The DRB1*11 and DRB1*13 alleles share a HLA-DRB1 gene sequence containing S in position 13, D in 70 and A in 74, and coding for the P4 pocket within the HLA-DR binding groove. This feature of the HLA-DRB1 gene could be involved in the K peptide presentation through a polymorphism ligand specific for the T193 (M) of K. In conclusion, this study demonstrated a high frequency of HLA-DRB1*11 or HLA-DRB1*13 alleles in K immunised patients, which could be due to specific K peptide presentation by HLA-DR molecules.
authors.affiliation: EFS Alpes-Méditerranée, Biology, Marseille, France. jacques.chiaroni@efs.sante.fr
authors.forename: Jacques
authors.initials: J
authors.lastname: Chiaroni
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dettori
authors.forename: Virginie
authors.initials: V
authors.lastname: Ferrera
authors.forename: Dominique
authors.initials: D
authors.lastname: Legrand
authors.forename: Mhammed
authors.initials: M
authors.lastname: Touinssi
authors.forename: Pierre
authors.initials: P
authors.lastname: Mercier
authors.forename: Philippe
authors.initials: P
authors.lastname: de Micco
authors.forename: Denis
authors.initials: D
authors.lastname: Reviron
mesh_terms: D000483:Alleles; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D001803:Blood Transfusion; D000939:Epitopes / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics* / Q000276:immunology; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy
chemical_list: D000942:Antigens, Bacterial; D000954:Antigens, Surface; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C508422:HLA-DRB1*11 antigen; C506473:HLA-DRB1*13 antigen; C030659:K antigens; D007626:Kell Blood-Group System