MICROSATELLITE TYPING: A RAPID METHOD FOR DETECTING BONE MARROW TRANSPLANT COMPATIBILITY

Abstract

The success of engraftment in bone marrow transplantation is dependent upon antigen compatibility between donor and recipient. The gene products of the major histocompatibility complex, also known as human leukocyte antigen (HLA), and minor histocompatibility antigens (mHAg) are recognized by T lymphocytes and are associated with inducing an immune response. Antigen compatibility is the primary factor in prevention of graft versus host disease (GVHD). Traditionally, compatibility between donor and recipient has been tested by HLA typing using serologic methods and more recently by molecular methods. Serologic methods are often not sensitive enough to detect differences at the HLA loci and molecular methods do not detect relevant differences outside the HLA region. Where additional histocompatibility loci may be located, this study examined the use of microsatellite typing at nine loci, within and near the HLA region, to determine if it would be a more accurate and rapid method of detecting compatibility between related bone marrow donors and recipients. Ninety-two sibling pairs were typed using both HLA and microsatellite methods. To determine concordance in matching sibling pairs, results from the two methods were compared. First, 4 microsatellite markers located between the regions of DQB1 and HLA-A (2700 kb) were compared to HLA data. Second, all 9 microsatellite markers extending from D6S291 (centromeric) to D6S276 (telomeric) (12-14 MB) were compared to HLA typing. When microsatellite markers between HLA-A and HLA-DQ were compared with HLA typing, microsatellite typing was concordant in 80 cases, while 12 cases showed discordant results. Microsatellite typing was concordant with HLA in 71 cases, while 21 cases showed discordant results when microsatellite markers extending from D6S291 to D6S276 were compared with HLA results. For each sibling pair that was discordant, the clinical data showed that the engrafted patients developed GVHD. The data indicated that microsatellite markers, which cover a greater distance than HLA alone, were more sensitive in detection of incompatibilities. Microsatellite typing is 20% more efficient in detecting sibling pair mismatches. Microsatellite typing along with HLA typing is a more sensitive method to detect HLA associated mismatches than HLA typing alone. This data supports the use of microsatellite testing before transplantation to identify discordant alleles between siblings in the regions flanking the MHC and within the HLA typed region.