Serum Siderocalin Measured in Patients with TB and HIV

The progression from uninfected or latently infected to active TB is often insidious and has minimal symptoms in the initial months, resulting in delayed diagnosis and poor outcomes.

Mycobacterium tuberculosis produces high-affinity siderophores that play essential roles in iron acquisition and tuberculosis (TB) pathogenesis. In response, host cells secrete a siderophore-binding protein, siderocalin, to limit the bacteria’s access to iron. Human immunodeficiency virus (HIV) infection is well known to be associated with enhanced susceptibility to TB, but it is not clear whether alterations in siderocalin levels contribute to this susceptibility.

A team of scientists working with the Christian Medical College (Vellore, India) quantified serum siderocalin levels were quantified in four sets of individuals: HIV-infected patients with TB (HIVpos, TBpos), non-HIV-infected patients with TB (HIVneg, TBpos), HIV-infected patients without TB (HIVpos, TBneg), and healthy controls (HIVneg, TBneg). Serum samples from recruited patients were stored at −70°C and were used at the end of the study period for estimations.

TB was diagnosed by mycobacterial culture or Xpert MTB/RIF assay. Siderocalin was assayed using the neutrophil gelatinase-associated lipocalin (NGAL) enzyme-linked immunosorbent assay (ELISA) kit. The lower and upper limits of detection were 10 pg/mL and 1,000 pg/mL, respectively. Values outside these limits were recorded as being out of range.

The team reported that in the absence of TB, the median siderocalin concentration in healthy HIV-negative controls and HIV-positive individuals was 453 pg/mL and 268 pg/mL, respectively. TB infection considerably increased the siderocalin concentrations in each group. Specifically, HIVneg, TBpos patients had a median siderocalin concentration of 920 pg/mL, which was significantly higher compared to the HIVneg, TBneg controls. Similarly, HIVpos, TBpos patients had a median siderocalin concentration of 494 pg/mL, much higher than the HIVpos, TBneg controls. In addition, the difference between the mean siderocalin concentrations of HIVneg, TBpos (920 pg/mL) and HIVpos, TBpos (494 pg/mL) patients were found to be statistically significant. The median CD4 count in the HIVpos, TBneg controls were 302 (26–451) cells/μL, and among HIVpos, TBpos subjects was 93 (13–445) cells/μL. The difference in neutrophil counts between the HIVneg, TBneg and HIVneg, TBpos groups was also found to be statistically significant.

The authors concluded that their results indicate that active TB leads to an up-regulation of serum siderocalin regardless of HIV status, whereas HIV infection leads to a down-regulation of serum siderocalin levels in both TBneg and TBpos individuals. Further studies are needed to evaluate siderocalin as a potential marker of active TB and to clarify its role in the pathogenesis of HIV-associated TB. The study was published in the August 2019 issue of the International Journal of Infectious Diseases.

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