Robert O. Endres

101-P: IDENTIFICATION OF NOVEL ASSOCIATIONS BETWEEN DRB1∗01 AND DRB5 USING MOLECULAR METHODS

Aim Linkage disequilibrium between HLA-DRB1, DRB3/4/5, and DQB1 has been well described in immunology literature. DRB1 ∗ 03, ∗ 11, ∗ 12, ∗ 13, ∗ 14 are linked to DRB3; DRB1 ∗ 04, ∗ 07, ∗ 09 are linked to DRB4; and DRB1 ∗ 15, ∗ 16 are linked to DRB5. The genes encoding DRB1 ∗ 01, ∗ 08, ∗ 10 are normally not linked with any DRB3/4/5 genes. We present two examples of individuals expressing a DRB1 ∗ 01, DRB5, DQB1 ∗ 05 association. Methods Subjects were typed at the HLA-DRB1, DRB3/4/5, and DQB1 loci using either polymerase chain reaction with sequence-specific primers or sequence base typing methods. Data on previously typed patients and donors was mined from the laboratory HistoTrac database. Results Of the unrelated subjects previously typed at DRB1, DRB3/4/5, and DQB1, 428 expressed at least one DRB1 ∗ 01 allele, and 16.6% of these (71/428) expressed at least one DRB5 allele. Of those subjects expressing DRB5, 78.9% (56/71) typed as DRB1 ∗ 01:01, 11.3% (8/71) as DRB1 ∗ 01:02, and 9.8% (7/71) as DRB1 ∗ 01:03. Only two subjects (2.8%, 2/71) possessing DRB5 and either DRB1 ∗ 01:01or DRB1 ∗ 01:02, lacked the expected DRB1 ∗ 15 or ∗ 16 second allele commonly associated with it. None of the 635 potential donors for transplant patients that expressed at least one DRB1 ∗ 01 allele were found to express a DRB5 allele without a DRB1∗15 or ∗ 16 allele. Based on the DRB1, DRB3/4/5, and DQB1 genotpes of the two individuals identified to express DRB5 alleles which were not associated with DRB1 ∗ 15 or ∗ 16, it appeared that DQB1 ∗ 05:01 was also present in the DRB1 ∗ 01 haplotypes associated with DRB5 ∗ 01:01(DRB1 ∗ 01/DRB5 ∗ 01:01/DQB1 ∗ 05:01and DRB1 ∗ 07/DRB4/DQB1 ∗ 02:02). At high resolution, one typed as DRB1 ∗ 01:02, and the other typed as DRB1 ∗ 01:01. Conclusions The etiology of the newly described association between DRB1 ∗ 01 and DRB5 is currently unknown. Given the dynamic nature of gene interaction, relying on established DRB1, DRB3/4/5, DQB1 associations is insufficient, as this case study exemplifies.