Plasma levels of CRP, neopterin and IP-10 in HIV-infected individuals with and without pulmonary tuberculosis

Introduction: Tuberculosis (TB) is a major cause of morbidity and death worldwide, and disproportionally affects people with HIV. Many cases still remain undiagnosed, and rapid and effective screening strategies are needed to control the TB epidemics. Immunological biomarkers may contribute. Methods: Plasma samples from healthy individuals (n: 12) and from HIV-infected individuals with (n: 21) and without pulmonary TB (n: 122) were tested for C-reactive protein (CRP), neopterin, and interferon-gammainducible protein-10 (IP-10). Increased levels of biomarkers and WHO 4-symptom-screening were compared with the presence of pulmonary TB. Survival status at 12 months was recorded. Associations with CD4 count, BMI, haemoglobin, disease severity, and mortality were analysed. Results: The plasma levels of the biomarkers were significantly higher in TB-positive (n:21) compared to TBnegative (n:122) subjects. WHO symptoms, increased neopterin (>10 nmol/L) and CRP (>10 mg/L) showed similar sensitivity and different specificity, with increased CRP showing higher and increased neopterin lower specificity. The three markers were inversely correlated to haemoglobin and to CD4, and CRP levels inversely correlated to BMI. The markers were also significantly higher in individuals with subsequent mortality and in individuals with higher mycobacterial load in sputum according to Xpert results (IP-10 and CRP). Conclusion: This study showed significant associations of the biomarkers analysed with TB infection and mortality, that could have potential clinical relevance. Biomarker levels may be included in operational research on TB screening and diagnosis.