Effect of disparity in the newly identified minor histocompatibility antigen SKH13 on the development of graft-versus-host disease after marrow transplantation from an HLA-identical sibling

We have identified a new HLA 0201-restricted minor histocompatibility antigen encoded by the KIAA0020 gene and recognized by CD8+ cytotoxic T cells (CTL) derived from a patient with chronic GVHD (Brickner et al, submitted). This antigen, termed HA-8, results from a proline (P) to arginine (R) substitution at position 149 of the KIAA0020 protein (position 1 of the antigenic epitope). Peptides containing both R and P at position1 bind HLA A201 when pulsed onto cells in vitro but expression of minigene construcis encoding these peptides demonstrated that only the peptide containing R is appropriately processed and transported into the endoplasmic reticulum. KIAA0020 is broadly expressed in tissues with the highest levels in lung and liver. A PCR-RFLP method for genotyping KIAA0020 was developed and a retrospective analysis was performed to evaluate the effect of HA-8 disparity on GVHD after HLA identical sibling transplant. Genomic DNA samples from 235 Caucasian donor/recipient pairs previously used for the analysis of HA-1 disparity (Tseng et al, Blood 94: 2911, 1999) were used for this study. All patients received methotrexate and cyclosporin for GVHD prophylaxis. Of 235 patients, 25 (10.6%) received an HA-8 incompatible transplant and 210 (89.4%) received an HA-8 compatible transplant. Grade II - IV acute GVHD occurred in 12 (48.0%) of the HA-8 incompatible and 45.2 % of the HA-8 compatible recipients (p =.79). Clinical or pathologi c chronic GVHD was diagnosed in 18/25 (72%) of incompatible recipients compared with 114/210 (54%) compatible recipients (p =.09). These results suggest a potential association of HA-8 disparity with cGVHD. An HLA A2/HA-8 tetramer has been constructed and s being used prospectively to identify HA-8 specific T cells in blood and tissues after allogeneic BMT.