The Pathogenesis Of Immune Reconstitution Inflammatory Syndrome Of AIDS Patients Receiving Highly Active Antiretroviral Therapy

Objective:our research aimed at studying the changes of the cytokines before and after receiving HAART in IRIS patients, exploring the effects of cytokines to the development of IRIS, the influence of NFAT and its target genes to IRIS development and progression, and providing evidence for the clinical IRIS diagnosis and treatment.Methods:(1) Screen differentially expressed genes of the IRIS patients by using Agilent Whole Human Genome Oligo Microarray, and preliminarily determine the main types of immune cells and the main signal pathway of the IRIS patients.(2)Summarize the changes of the plasms immune molecules and cytokines of IL4, IL6, IFNy, IL10, IL18, IL12p40, MCP-1, IL8, IL17A in IRIS patients before and receiving HAART;(3) we studyed the genes expression of NFAT1, NFAT2, NFAT4and its major target genes IL6, IL8, TNFa, IL1β,IL10, IL2, IL18in peripheral blood CD3+T cells of IRIS patients through fluorescence quantitative PCR, and explored the changes of these genes.Results:The mean time of HAART when IRIS happened was31days, and the concentration of IL4, IL12p40, IL18was higher in IRIS patients than non-IRIS patients before receiving HAART(P<0.05); when HAART at1month, IRIS patients’plasma IL4, IL6, IFNy, IL12p40, IL18, MCP-1were higher than the non-IRIS and were statistically significant (P<0.05). The IRIS patients had higher plasma concentration of L6, IL4, ILO, IL12p40when receiving HAART1month than0month(P>0.05). And the genes exxpression of NFAT1, IL6, IL8, TNFa of CD3+T cells increased after1month of HAART in IRIS patients, while the non-IRIS patients had lower expression of NFAT4, NFAT2, NFAT1, IL1β, IL6, IL8, IL10, IL2, IL18than HAART beginning. And the IRIS patients had lower expression of NFAT1, IL6, IL8than the non-IRIS patients at HAART beginning, while HAART1month later, the expression of NFAT1, NFAT2, NFAT4, IL6, IL8, TNFa, IL1β, IL10, IL2, IL18were all higher in the IRIS patients than the non-IRIS patients.Conclusion:(1)The study suggested high concentration of IL4, IL12p40， IL18can predict the risk of IRIS.(2)IL4, IL6, IFNy, IL12p40, IL18, MCP-1may paly a role in the pathogenesis of IRIS.(3) the increasing gene expression of NFAT1may promote the expression of cytokines, such as IL6, IL8, TNFa, which may increase the occurance of IRIS.