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

Research Highlight

Earliest signs of active TB revealed



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.

Supported content

  1. Proceedings of the National Academy of Sciences USA 115, E964–E973 (2018). doi: 10.1073/pnas.1711853115
Institutions FC
The Francis Crick Institute, United Kingdom (UK) 0.26
UCT Institute of Infectious Diseases and Molecular Medicine (IDM), South Africa 0.17
UCT Department of Medicine, South Africa 0.17
Immunoregulation and Infection Laboratory, The Francis Crick Institute, United Kingdom (UK) 0.15
Department of Medicine (DOM), ICL, United Kingdom (UK) 0.05
National Heart and Lung Institute (NHLI), ICL, United Kingdom (UK) 0.05
UCT School of Public Health and Family Medicine, South Africa 0.03
UCT Division of Medical Microbiology, South Africa 0.03
Oxford Radcliffe Department of Medicine (RDM), United Kingdom (UK) 0.03
Faculty of Medicine and Health Sciences, SU, South Africa 0.02
NIH NIAID Tuberculosis Research Section (TBRS), United States of America (USA) 0.02
UCT Faculty of Humanities, South Africa 0.02