However, we also observed a correlation between neopterin levels and CD4 cell counts in HIV-negative TB patients. Since subnormal CD4 cell counts have been reported in apparently healthy HIV-negative individuals from different countries in sub-Saharan Africa (including the region where our study was conducted [24]), we also analyzed CD4 cell count, neopterin and CRP in healthy controls. association with CD4 cell levels, and decided their predictive capacity as alternate markers of advanced immunosuppression. Methods Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The overall performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Results Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 g/ml, HIV-/TB+ 33 g/ml, controls 0.5 g/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers experienced adequate predictive value SR-2211 for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Conclusion Neopterin levels were high in adults with TB, SR-2211 both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as option assessments for immunosuppression in patients coinfected with HIV and TB. Introduction TB is the most common opportunistic contamination (OI) and cause of death in people living with HIV (PLHIV) globally, with the highest case burden in sub-Saharan Africa [1]. In HIV-positive persons the risk of active TB is usually inversely correlated to CD4 cell levels [2]. Although CD4 cell depletion is usually characteristic of HIV disease, subnormal CD4 cell levels can occur in other conditions [3], which may coexist in PLHIV. This includes active TB [4C6]; however the mechanisms involved in TB-related CD4 lymphocytopenia are unclear. In HIV contamination, the main cause of CD4 cell depletion and disease progression is chronic immune activation [7,8]. Low-grade chronic immune activation is mainly caused by bacterial translocation from your gastrointestinal tract [9]. However, it is also possible that OI:s could contribute to immune activation (IA), thus creating a vicious spiral in HIV-infected subjects with pre-existent immunosuppression [10]. A central component in the pathogenesis of TB is the activation of macrophages by T-cells. We hypothesized that IA may be involved in CD4 cell SR-2211 lymphocytopenia also in HIV-negative individuals with TB. We have recently reported a relationship between CD4 cell levels and disease severity in a cohort of Ethiopian TB patients with and without HIV coinfection [4]. In the present study, we aimed to investigate IA in TB-related CD4 lymphocytopenia by determining plasma levels of neopterin and CRP (reflecting immune activation and systemic inflammation, respectively) in cohort participants in relation to CD4 cell count SR-2211 before and after anti-TB treatment. In addition, we aimed to investigate the potential use of these plasma markers as option tests for assessment of HIV-related immunosuppression in TB/HIV coinfection. Methods Study participants Participants were selected and retrospectively analyzed ATN1 from a prospective cohort study encompassing 1116 TB patients (307 HIV+, 809 HIV-negative; explained SR-2211 in detail previously), with the overall aim to investigate immunosuppression in TB with and without HIV coinfection [4,11]. Patients were recruited and followed up at eight outpatient TB clinics (based in 6 health centers, 1 regional hospital and 1 zonal hospital) in the Oromia region, Ethiopia, between September 2010 and September 2012. Inclusion criteria were: diagnosis of active TB, age 18 years or greater, residence in the medical center uptake area, and consent to HIV screening. Subjects having received ATT for more than 2 weeks for their current episode of TB, or who had been treated for TB within the preceding 6 months were excluded, as were persons with current or previous antiretroviral therapy (ART). A control group of healthy individuals was recruited at a voluntary HIV counseling and testing medical center located at one of the study health centers. HIV-negative subjects without signs or symptoms suggestive of TB or other illness were eligible.