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.
Highlights
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
After verifying that there was no association between these IL-7 gene variants and low pre-ART CD4+ T-cell counts (CD4+ T-cell ≤ 200 cells/μL) (Figure S1-C, cases versus controls), we investigated whether there was any association with poor ART-associated immune response (Figure S1-C, Immunological nonrecoverers (INR) versus immunological recoverers (IRs))
Whereas an increase in IL-7 production has www.nature.com/scientificreports been proposed as part of the homeostatic response to T-cell depletion[16] and relates lower pre-ART IL-7 levels to faster CD4+ T cell recovery[18], other studies suggest an association between lower concentrations of the IL-7/IL-7R axis with an insufficient ability to restore the number of CD4+ T cells in response to ART14,21
Summary
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. One of the objectives of antiretroviral treatment (ART) is to improve the prognosis of HIV-infected subjects due to the decrease of HIV replication below detectable levels and due to CD4+ T-cell count recovery, achieving cell counts that preclude patients from the risk of opportunistic infections. While this goal is achieved in a substantial proportion of patients, up to 30% of infected subjects who successfully suppress viremia below the limit of detectability do not obtain sufficient CD4+ T-cell gains[2]. IL-7 and IL-7R plasma levels were evaluated in baseline samples of HIV-infected subjects who first began ART and again after 48 and 144 weeks of follow-up under the ART regimen
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