IL-7/IL-7R gene variants impact circulating IL-7/IL-7R homeostasis and ART-associated immune recovery status

Abstract

A relationship between polymorphisms in genes encoding interleukin 7 (IL-7) and its cellular receptor (IL-7R) and antiretroviral therapy (ART)-associated immune recovery in HIV subjects has been previously reported. However, details of this relationship remain unclear, and the association of these polymorphisms with circulating IL-7/IL-7R levels is scarce. Here, we explored whether IL-7/IL-7R axis was associated with quantitative CD4+ T-cell recovery in HIV-infected subjects. IL-7/IL-7R polymorphisms were assessed by genotyping, and multiple inheritance models were used to estimate both, their association with low pre-ART CD4+ T-cell counts and incomplete immune recovery status after 48 weeks of suppressive ART. Integrated data from genetic variants association and soluble plasma IL-7/IL-7R quantification suggest that IL-7/IL-7R genotype expression could alter the homeostatic balance between soluble and membrane-bound receptors. The haplotype analyses indicates that allele combinations impacts pre-ART circulating CD4+ T-cell counts, immune recovery status and the absolute increment of CD4+ T-cell counts. The knowledge about how IL-7/IL-7R axis is related to quantitative CD4+ T-cell recovery and immune recovery status after initiating ART could be useful regarding T-cell reservoirs investigations in HIV subjects.