HLA‐DRB1 polymorphism is associated with Kell immunisation

Summary 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.