HETEROGENEITY OF HLA-B35 - OLIGOTYPING AND DIRECT SEQUENCING FOR B35 SUBTYPES REVEALS A HIGH MISMATCHING RATE IN B35 SEROLOGICALLY COMPATIBLE KIDNEY AND BONE MARROW DONOR RECIPIENT PAIRS

We used a simple HLA-B35 PCR/SSO-oligotyping procedure, combined with exon 3 direct sequencing for the analysis of B35 subtype frequencies i n our population, and for the evaluation of the degree of B35-subtype compatibility in serologically matched unrelated bone marrow and Kidne y transplant pairs, B3501 was the most frequent allele (0.6), followe d by B3503 (0.19), B*3502 (0.13), B*3508 (0.07), and B*3505 (<0.01). HLA-B35-subtype matching of donors and recipients was strongly depende nt on the stringency of ABDRB1 matching. Among 10 kidney donor/recipie nt pairs, only 30% were B35-subtype-matched. Due to the lack of ABDRB1 haplotype matching, this low degree of matching was not better than w hat would be expected on the basis of the subtype frequency distributi on in the population. In contrast, HLA-B35 subtype compatibility was h igher in unrelated bone marrow donor/recipient pairs that were serolog ically ABDR-matched: 30 of the 62 (48.4%) B35-positive combinations te sted were B35-subtype-compatible. When all patient/donor plus donor/do nor combinations (n=160) were taken into account, 46% of the ABDR-matc hed pairs were B35-subtype-compatible. When only pairs that were DRB1/ DRE3/DRB5-subtype-matched by oligotyping (n=62) were considered, 71% w ere B35-subtype-compatible. The fact that a significant percent of pat ient/donor pairs matched by conventional HLA-typing are found incompat ible, as shown here for B35, explains the difficulties in assessing th e beneficial effect of HLA matching in transplantation.