Changes in the balance of Th17/Treg cells and oxidative stress markers in patients with HIV‑associated pulmonary tuberculosis who develop IRIS

Abstract

Tuberculosis (TB) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) infection and is one of the primary causes of death from AIDS. The increased accessibility to highly active antiretroviral therapy (HAART) has significantly improved the clinical outcome of patients with HIV infection. However, following ART, rapid restoration of the immune system leads to immune reconstitution inflammatory syndrome (IRIS). Oxidative stress and innate immunity play a role in TB-associated IRIS (TB-IRIS). The present study investigated the changes that occur in oxidative stress markers and T helper (Th)17/regulatory T (Treg) cell balance and their significance in IRIS patients with HIV-associated pulmonary TB. A total of 316 patients with HIV-associated pulmonary TB were treated with HAART and followed up regularly for 12 weeks. Those who developed IRIS were included in the IRIS group (n=60), while the remaining patients were included in the non-IRIS group (n=256). The changes in plasma oxidative stress markers superoxide dismutase (SOD) and malondialdehyde (MDA) were detected with the ELISA, and the ratio of Th17 to Treg cells in whole blood were analyzed before and after treatment through the flow cytometric assay. Following treatment, MDA and Th17 cells levels were significantly increased while SOD and Treg cells levels were decreased in the IRIS group (P<0.05) compared with before treatment. In the non-IRIS group, a non-significant decrease was observed in SOD levels (P>0.05), while the MDA levels significantly decreased compared with before treatment (P<0.05) and the Th17 and Treg cells levels were both significantly increased (P<0.05). After treatment, compared with the non-IRIS group, the IRIS group showed a significant increase in MDA and Th17 cells and decrease in SOD and Treg cells levels (P<0.05). In addition, Th17 cells levels were positively correlated with MDA but negatively correlated with SOD levels. Treg levels were negatively correlated with MDA and positively correlated with SOD levels (P<0.05). The area under the curve values of serum MDA and SOD, Th17 and Treg levels predicting the occurrence of IRIS were 0.738, 0.883, 0.722 and 0.719, respectively (P<0.05). These results indicated that the above parameters have certain diagnostic value for the occurrence of IRIS. The occurrence of IRIS in patients with HIV-associated pulmonary TB may be associated with oxidative stress and Th17/Treg cell imbalance.

The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV

“…There are no concrete answers regarding GSH as a therapy option for the management of IRIS at the moment. However, a 2023 study followed 316 patients in China over 12 weeks of HAART therapy and found increases in malondialdehyde (MDA) and Th17 cell counts and decreases in superoxide dismutase (SOD) and Treg levels [ 71 ]. This constellation of findings indicates that GSH supplementation may be a viable treatment option for patients with IRIS or as a prophylactic agent in patients starting HAART.…”

Glutathione in HIV-Associated Neurocognitive Disorders

“…In IRIS, the immune response is overly robust and causes injury to the host. Patients with IRIS will have increased malondialdehyde levels, increased Th17 cell counts, decreased superoxide dismutase levels, and decreased Treg cell counts [ 115 ]. Our lab also found that glutathione seems to stabilize Th17 cell counts, evidenced by stabilized IL-17 levels after liposomal glutathione supplementation [ 56 ].…”