Genetics of graft‐versus‐host disease, I. A locus on Chromosome 1 influences development of acute graft‐versus‐host disease in a major histocompatibility complex mismatched murine model

Department of Biology, Indiana University-Purdue University at Indianapolis, IN, USA.
Immunology (Impact Factor: 3.8). 02/1999; 96(2):254-61. DOI: 10.1046/j.1365-2567.1999.00626.x
Source: PubMed


Graft-versus-host disease (GVHD) is the major complication occurring after bone marrow transplantation. The severity of GVHD varies widely, with this variation generally being attributed to variation in the degree of disparity between host and donor for minor histocompatibility antigens. However, it is also possible that other forms of polymorphism, such as polymorphisms in immune effector molecules, might play a significant role in determining GVHD severity. In order to investigate this hypothesis, we are studying the genetic factors that influence GVHD development in a murine model. We here report the first results of this analysis, which demonstrate that a locus on Chromosome 1 of the mouse, and possibly also a locus on Chromosome 4, exert considerable influence over the development of one aspect of acute GVHD - splenomegaly - in a parent-->F1 murine model. These results demonstrate that non-MHC genes can exert quite significant effects on the development of GVHD-associated pathology and that gene mapping can be used as a tool to identify these loci. Further analysis of such loci will allow identification of the mechanism whereby they influence GVHD and may lead in the future to improved selection of donors for human bone marrow transplantation.

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    • "Over 80 QTLs are listed at the mouse genome database (36) and a number of cis and trans eQTLs have been characterized (37). Among them, several QTLs are involved with complex inflammatory reaction, such as graft vs. host disease (38) lupus (39), modifier of LPS-response (40), and susceptibility to tuberculosis (41). "
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    • "Some non-MHC loci that modify alloresponse were shown to be minor antigens coded in the mouse by Mtv [13]. Several groups have reported that recognition of a host vSAG (viral superantigens) (Mls1a and Mls2a) by donor T cells may determine the manifestations of GVHD in several parental/F1 strain combinations [14] [15], others indicate roles of non-MHC non-Mls genes in MLR [16] [17] and in GVHD [18] [19] [20] [21]. "
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