Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis

Earliest signs of active TB revealed

28 September 2018

Latent tuberculosis may not always be so latent after all. Researchers have discovered that some people diagnosed with this non-active form of the bacterial infection show early immunological signs of progression to full-blown disease. This finding could spur the development of predictive blood tests and new drug interventions.

A team that included scientists from the University of Cape Town analysed gene expression patterns in the blood of 35 HIV-infected people diagnosed with latent tuberculosis, 10 of whom showed radiographic evidence of early active disease — a condition termed ‘subclinical’ tuberculosis. 

Like patients with active tuberculosis, but unlike those with truly latent infections, individuals with subclinical disease expressed many genes involved in mounting a specific type of immune response involving the so-called ‘classical complement pathway’. These patients also showed increased levels of disease-linked ‘immune complexes’ and the receptors that bind them.

HIV co-infection makes the progression of tuberculosis more likely, but this subclinical disease phenomenon may be more general, as the same immune-related gene signature was also present in an HIV-uninfected cohort during the year leading up to active tuberculosis presentation.

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References

1. Proceedings of the National Academy of Sciences USA 115, E964–E973 (2018). doi: 10.1073/pnas.1711853115