TREX1 531C/T Polymorphism and Autoantibodies Associated with the Immune Status of HIV-1-Infected Individuals

Abstract

Autoimmune diseases can develop during HIV-1 infection, mainly related to the individual’s immune competence. The study investigated the association of the TREX1 531C/T polymorphism and antinuclear antibodies (ANA) in HIV-1 infection and the time of antiretroviral therapy (ART) used. Cross-sectional and longitudinal assessments were carried out in 150 individuals, divided into three groups: ART-naïve, 5 years and 10 years on ART; ART-naïve individuals were evaluated for 2 years after initiation of treatment. The individuals’ blood samples were submitted to indirect immunofluorescence tests, real-time PCR and flow cytometry. The TREX1 531C/T polymorphism was associated with higher levels of TCD4+ lymphocytes and IFN-α in individuals with HIV-1. Individuals on ART had a higher frequency of ANA, higher levels of T CD4+ lymphocytes, a higher ratio of T CD4+/CD8+ lymphocytes and higher levels of IFN-α than therapy-naïve individuals (p < 0.05). The TREX1 531C/T polymorphism was associated with better maintenance of the immune status of individuals with HIV-1 and ANA with immune restoration in individuals on ART, indicating the need to identify individuals at risk of developing an autoimmune disease.

The Expression Levels of TREX1 and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals

“…Thus, it is possible that the frequencies of the investigated polymorphisms may be associated with HIV-1 infection only in certain ethnic groups. Another example is the TREX1 polymorphism rs11797 (C/T), which was associated with HIV-1 infection in the same population as in the previous study [ 6 ], but not in the study that evaluated the polymorphism in a population of different ethnicities [ 22 ].…”

“…Given that ANA were present in individuals after ART, who had higher IFN-α levels, these individuals may have experienced a more pronounced recovery of immune competence, which proves to be independent of the type of therapeutic regimen used. Other studies have described the association of ART use with the recovery of immune competence and the development of ANA [ 3 , 6 ]. Screening for ANA in individuals with HIV-1 infection who are receiving ART is important for identifying who could be at risk for developing possible autoimmune manifestations [ 6 ].…”

“…Because there is still no treatment available to eradicate the infection, the main control measure is antiretroviral therapy (ART), which promotes a reduction in viral load to undetectable levels, allowing the restoration of the individual’s immune response [ 2 , 3 ]. Unfortunately, ART may contribute to the development of metabolic changes and autoimmune reactions [ 3 , 4 , 5 , 6 ].…”

“…Genetic variations in different cytosolic sensors that may influence the course of autoimmune diseases and viral infections have been investigated [ 18 , 19 ]. Polymorphisms in the TREX1 gene were associated with autoimmune manifestations, such as systemic lupus erythematosus and Sjögren’s syndrome [ 20 , 21 ], and with retrovirus infection [ 6 , 18 , 22 ]. Among the various polymorphisms located in the TREX1 gene, some stand out in HIV-1 infection; the TREX1 rs3135941 (T/C) polymorphism was related to faster progression of the infection [ 23 ], and the TREX1 rs3135945 (G/A) polymorphism was associated with susceptibility to virus infection [ 22 ].…”

“…Among the various polymorphisms located in the TREX1 gene, some stand out in HIV-1 infection; the TREX1 rs3135941 (T/C) polymorphism was related to faster progression of the infection [ 23 ], and the TREX1 rs3135945 (G/A) polymorphism was associated with susceptibility to virus infection [ 22 ]. The TREX1 rs11797 (C/T) variation is associated with the maintenance of the immune status of individuals with HIV-1 [ 6 ]. However, in human T-cell leukemia virus type 1 (HTLV-1) infection, the TREX1 rs11797 (C/T) polymorphism was associated with a high proviral load [ 18 ].…”