Genetic Polymorphisms in Chemokine Receptor 5, Interleukin 10 and Monocyte Chemoattractant Protein 1 Contribute to Cytomegalovirus Reactivation and Disease after Allogeneic Stem Cell Transplantation.

Human Cytomegalovirus (HCMV) infection is still one of the most challenging complications after allogeneic stem cell transplantation (alloSCT). Here, we demonstrate that defined single nucleotide polymorphisms (SNPs) are associated with the susceptibility to HCMV infection after alloSCT.

Genotyping of 83 patients (with HCMV reactivation) and 71 controls (no HCMV reactivation) was performed. All donors and SCT recipients were Caucasians. Patients suffered from chronic myeloproliferative disorders (n = 16) and AML /ALL /SAA /NHL /MDS (n = 117). For 21 patients, underlying disease could not be determined retrospectively. Genotyping was performed by Pyroseqencing^TM on the PSQ^TM HS96A System (Biotage AB, Uppsala Sweden) or on ABI 7900 ABI PRISM® Sequence Detection System using TaqMan® Assay-By-Design^TM and Assay-On-Demand ^TM (Applied Biosystems).

By Armitage’s-Trend-Test, no significant association for 78 /87 markers and the occurrence of HCMV reactivation or disease (p > 0.05) was found. However, 9 markers showed a significant association with HCMV reactivation and /or disease. These markers are located in CCR5, MCP 1and IL10. If comparing individuals with HCMV-DNAemia versus no reactivation regardless of disease, 5 markers showed a significant association (in MCP 1and IL10). Two markers of MCP 1were significantly associated with HCMV reactivation, but none of the markers analyzed in CCR5 and IL10. Thus, we presume that HCMV reactivation is associated with polymorphisms in MCP1, whereas disease might be related to polymorphisms in CCR5 and IL10. Analyzing the clinical parameters, we found an association between CD34 selection and HCMV reactivation (p = 0.0378) or HCMV disease (p = 0.001). Furthermore, severe acute GvHD was significantly related to HCMV disease (p = 0.0015), chronic GvHD was significantly associated to HCMV disease only if reactivation versus disease was compared (p = 0.034). Treatment with corticosteroids led to HCMV reactivation (p = 0.036). In conclusion, screening of alloSCT patients for the presence of defined polymorphisms may help to predict the individual risk of HCMV reactivation and disease, and thus justifying additional antiviral prophylaxis.