Multi-analyte profiling of ten cytokines in South African HIV-infected patients with Immune Reconstitution Inflammatory Syndrome (IRIS)

We determined the expression patterns of 10 cytokines by Luminex multi-analyte profiling in 17 IRIS nested case-control pairs participating in a prospective South African cohort initiating anti-retroviral therapy.Interferon-gamma (IFN-γ) expression was significantly elevated in IRIS cases compared to controls (median 9.88 pg/ml versus 2.68 pg/ml, respectively, P = 0.0057), while other cytokines displayed non-significant differences in expression. Significant correlation was observed between IL-6, IL-10, and IFN-γ expression in the IRIS patients.Significantly increased expression levels of IFN-γ suggest that this cytokine possibly plays a role in IRIS pathology and is a potential diagnostic marker.HIV infection leads to a progressive loss of CD4+ T cells and eventually to the onset of AIDS [1]. Highly active antiretroviral therapy (HAART) results in a dramatic reduction in AIDS-defining illnesses and mortality by inhibiting HIV replication with the subsequent recovery of CD4+ T cell numbers and the restoration of immune function [2-4]. Some patients experience immune reconstitution inflammatory syndrome (IRIS), or immune restoration disease (IRD), as a result of pathological responses induced during immune restoration following the initiation of HAART [5,6]. IRIS is characterized by a paradoxical worsening of a pre-existing, or unmasking of a previously sub-clinical infection in the first weeks of HAART [7]. The immune response that causes IRIS is both excessive and unregulated, as the rapid restoration of immune function after initiating HAART leads to upregulated cell-mediated responses to live or dead infectious organisms or to antigens [2,8]. The resultant inflammation causes symptoms which can be severe. The presence of antigenic stimulus, whether infectious or non-infectious, is reportedly a pre-requisite to developing IRIS, and the incidence of IRIS is likely to be dependent on the underlying infectious burden [9,10]. In South Africa, where an estimated 5.2 mi