HLA-B*15 allele SNPs predict the serologically defined HLA-B15 split antigens

B. Duygu, B.M. Matern, C.M.H. Meertens, C.E.M. Voorter, M.G.J. Tilanus

Friday 16 march 2018

10:15 - 10:20h at Willem Burger Foyer

Categories: Basic, Session (poster)

Parallel session: Poster session 8: Basic translational research

Human leukocyte antigens (HLA) allow the immune system to discriminate self from non-self. Identification of HLA types of patients and donors is important for successful transplantation since HLA mismatches can trigger immune responses and antibody production. For a long time, HLA typing has been performed by serological typing methods, which measure cell reactivity against HLA antigens using a panel of sera containing well-characterized anti-HLA antibodies. This method enabled identification of the different serological HLA antigens including HLA-B15, which is a broad antigen group for B62, B63, B70 (B71 and B72), B75, B76, B77 split antigens (B15 subtypes). However, the scarcity of sera with specific anti-HLA antibodies makes the method inefficient to discriminate a high variety of HLA antigens. The advancements in DNA based technologies has led to a switch from serologic typing to high resolution DNA typing methods, but these DNA sequencing techniques assign all B15 antigens to the HLA-B*15 allele group. However, the presence of antibodies in the patient against split B15 antigens urges the identification of HLA-B*15 allele subtypes of the donor since the presence of Donor Specific Antibodies is an important contra-indication for kidney transplantation. Hence, we aimed to identify specific nucleotide motifs for each B15 subtype based on single nucleotide polymorphisms (SNP). We aligned the available full-length DNA sequences of B*15 alleles with assigned serological subtypes as defined in the HLA dictionary. This alignment leads to the identification of specific nucleotide motifs of each B15 split antigens at 10 different regions in exons 2 and 3 of B*15 alleles. A dataset of 107 B*15 alleles was used to verify that the nucleotide patterns were able to predict correct subtypes according to the expert assignment (HLA dictionary) and 97 were concordant. Moreover, the serological subtypes of two new B*15 alleles are identified and confirmed by serological typing. Next, we predicted for 110 B*15 alleles the serologic equivalents out of 128 B*15 alleles with unknown serological specificities (IPD-IMGT/HLA), only 18 alleles revealed inconclusive nucleotide patterns at the identified positions. Thus, this fast and reliable method enables prediction of B15 serological equivalents, of importance in case Donor Specific Antibodies are present, to prevent kidney transplant rejection.