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MHC class III polymorphisms in selection of donors for BMT
M T Dorak1, E A Chalmers, A M Sproul
1Department of Haematology, Glasgow Royal Infirmary, UK.
Bone Marrow Transplantation
|January 1, 1993
Summary
Class III typing improves matching for bone marrow transplants by identifying discrepancies missed by HLA and class II DNA matching. This ensures better MHC haplotype identity in unrelated donor selection.
Area of Science:
- Immunogenetics
- Transplantation immunology
Background:
- Current unrelated donor selection relies on HLA serological typing, class II DNA analysis, and MLR testing.
- Despite matching at DNA level for class II loci, a significant number of unrelated pairs remain MLR reactive.
Purpose of the Study:
- To evaluate the role of class III typing in determining MHC identity.
- To assess if class III typing can improve the accuracy of unrelated donor selection for bone marrow transplantation (BMT).
Main Methods:
- Investigated 86 donor/recipient pairs (14 unrelated) using C4, Bf, HSP70, and TNF DNA probes.
- Analyzed HLA serological matching, class II RFLP (DRB/DQB), MLR reactivity, and class III loci polymorphism.
Main Results:
- Phenotypically HLA-matched siblings were identical at the polymorphic C4 locus.
- Nine of 14 HLA serologically matched, MLR non-reactive unrelated pairs showed class III mismatching.
- Four of these mismatched pairs were DRB/DQB RFLP matched, highlighting limitations of current methods.
Conclusions:
- Serological identity, DRB/DQB RFLP matching, and negative MLR do not guarantee whole MHC haplotype identity in unrelated pairs.
- Class III loci typing is a reliable marker for whole MHC haplotype identity due to their linkage to both HLA regions.