Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis
© KATERYNA KON/SCIENCE PHOTO LIBRARY/Getty
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.
- Proceedings of the National Academy of Sciences USA 115, E964–E973 (2018). doi: 10.1073/pnas.1711853115