Allelic Variations in Genes Modulating Immune Function: Impact on Infections in Organ Transplantation

Susceptibility to infection after solid organ transplantation (SOT) reflects interactions among epidemiologic exposures, allograft-specific factors, pharmacologic immunosuppression and host innate and adaptive immune functions. Substantial variability in susceptibility to viral, bacterial, and fungal infections occurs among recipients despite comparable immunosuppressive regimens. Accumulating evidence demonstrates that allelic variation, including single nucleotide polymorphisms, occurs in genes involved in multiple aspects of innate immune function and influence infectious risk after SOT. These genes encode pattern recognition receptors, complement components, phagocyte and natural killer cells functions, soluble opsonins, and cytokines. These variants are associated with altered susceptibility to bacterial, invasive fungal, and viral infections including cytomegalovirus, Epstein-Barr virus, BK polyomavirus, and hepatitis viruses. The contribution of allelic variation to infectious susceptibility remains incompletely defined. Identification of high-risk genotypes may enable individualized infectious surveillance, tailored antimicrobial prophylaxis, and host-directed interventions to advance precision transplantation.