Zeitschrift für Knochenforschung
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Using Human Cytomegalovirus Glycoproteins to Prevent Graft versus Host Disease through Downregulation of Major Histocompatibility Complex Class I and Class II: A Novel Approach

Yasmeen AlSaif, Abdelhamid Liacini and Rabab Al Attas

Graft Versus Host Disease (GVHD) is an immune-mediated disease occurs as a complication of allogeneic Hematopoietic Stem Cell Transplantation (HSCT). Differences between donor and recipient Major Histocompatibility Complex (MHC) antigens initiate the disease. The immunocompetent cells of the donor recognize the cells of the immunocompromised host as non-self, thus commencing an immune response against them.

The human Cytomegalovirus (hCMV) is a member of the herpesvirus family that has developed strategies to escape the immune surveillance and defense system via encoding a series of glycoproteins that down regulate host MHC antigens. The Unique Short (US) hCMV glycoproteins US2, US3, US6, US10 and US11 have shown variable capabilities to downregulate MHC class I and II. Theoretically, these capabilities could be utilized to downregulate the expression of host MHC antigens, thus inhibiting the allograft recognition and the subsequent immune response, which would prevent GVHD. In this systematic review, 620 literatures have been identified through a PubMed, Epistemonikos, and Google Scholar search. An inclusion criterion has been applied to these studies, of which 27 have been selected.

This review found that the hCMV glycoproteins act as partner to downregulate MHC class I and class II, CMV glycoproteins regulate destruction of class I MHC molecules, and degrade MHC class II.
The Preferred Reporting Items for Systematic Reviews (PRISMA) Statement has been used to increase the quality of the review, and thus a Population Intervention Comparison Outcome Study design (PICOS) model has been formulated.
The findings of this research could be further studied and validated to offer an alternative approach to the current pharmacological preventive measures of GVHD, possibly without compromising patients’ immunity.