An Observational Case-Control Study to Determine Human Immunodeficiency Virus and Host Factor Influence on Biomarker Distribution and Serodiagnostic Potential in Adult Pulmonary Tuberculosis

Influence of host factors, including human immunodeficiency virus (HIV) co-infection, on the distribution and diagnostic potential of previously evaluated biomarkers of pulmonary tuberculosis (PTB), such as anti-antigen 60 (A60) immunoglobulin (Ig) G, anti-A60 IgA, and C-reactive protein (CRP), remain unclear. Anti-A60 IgG, anti-A60 IgA, and CRP in PTB and non-PTB patient sera (n = 404, including smear-positive/negative, culture-positive (SPCP/SNCP) and HIV+ve/-ve) were measured by enzyme-linked immunoassay and statistically analysed. In multinomial logistic regression, expectoration, chest pain, wasting, and culture count positively associated with CRP (p < 0.001), while smear count positively associated with anti-A60 IgG (p = 0.090). Expectoration and enlarged lymph nodes negatively associated with anti-A60 IgA (p = 0.018). Biomarker distribution and diagnostic potential varied significantly by symptoms and bacilli burden, and across different PTB subpopulations. CRP was correlated poorly with anti-A60 antibodies, while anti-A60 IgA and IgG were correlated in non-tuberculosis (TB) and SPCP patients (p < 0.001). When combined, anti-A60 IgG and CRP best discriminated SPCP/HIV-ve from non-TB (AUC: 0.838, 95% CI: 0.783⁻0.894), while anti-A60 IgA and CRP performed best in discriminating HIV+ve PTB from non-TB (AUC: 0.687, 95% CI: 0.598⁻0.777). Combined CRP and anti-A60 antibodies had significantly reduced accuracy in SNCP and SNCP/HIV+ve compared to SPCP/HIV-ve subpopulations. The complex relationships between host factors and biomarkers suggest their limited utility, especially in SNCP/HIV+ve subpopulations, highlighting the importance of examining host response and immune biomarkers across relevant patient subpopulations.