Tuberculosis (TB) and HIV infection are independently associated with elevated serum concentrations of tumour necrosis factor receptor type 1 and β2-microglobulin, respectively

Abstract

SUMMARY The aim of this study was to identify immune markers that are independently associated with HIV infection or TB in vivo. Using commercially available assays, we measured concentrations of five immune markers in sera from 175 out-patients attending medical clinics in Cote D'Ivoire and Ghana, West Africa. Patients were categorized into groups with TB only (TB+HIV−, n = 55), TB and HIV co-infection (TB+HIV+, n = 50), HIV infection only (TB−HIV+, n = 35), or neither infection (TB−HIV−, n = 35). TB+HIV+ and TB−HIV+ groups were matched for blood CD4+ lymphocyte count. Mean ±  s.d. concentrations of β2-microglobulin were similarly increased in both the TB−HIV+ (5·3 ± 2·1 μg/ml, P < 0·0001) and the TB+HIV+ (5·0 ± 1·5 μg/ml, P < 0·0001) groups compared with the TB−HIV− group (2·2 ± 1·8 μg/ml), but were only slightly increased in the TB+HIV− group (3·2 ± 1·8 μg/ml, P = 0·01). In contrast, mean serum concentrations of soluble tumour necrosis factor receptor type I (sTNF-RI) were similarly elevated in the TB+HIV− (1873 ± 799 pg/ml, P < 0·0001) and TB+HIV+ (1797 ± 571 pg/ml, P < 0·0001) groups compared with uninfected subjects (906 ± 613 pg/ml), but there was only a small increase in sTNF-RI in the TB−HIV+ group (1231 ± 165 pg/ml, P = 0·03). Both TB and HIV infection were associated with substantial elevation of serum concentrations of soluble CD8, soluble CD54, and sTNF-R type II. Analysis of additional samples from groups of TB+HIV− and TB+HIV+ patients receiving anti-TB treatment showed significant and equal reductions in mean serum sTNF-RI concentrations, but no significant change in mean β2-microglobulin. Thus, serum β2-microglobulin and sTNF-RI serve as relatively independent markers of HIV infection and TB, respectively, in studies of co-infected persons.