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Altered immune responses at TB diagnosis predict relapse
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Patients who relapsed with tuberculosis were likely to have excessive cytolytic responses to Mycobacterium tuberculosis in vitro when first diagnosed, according to recent study results.
The findings represent a potential biomarker for TB relapse and could aid in the development of new treatments, researchers said.
Jacqueline M. Cliff, PhD, from the London School of Hygiene & Tropical Medicine, and colleagues evaluated 263 untreated patients with smear-positive TB results who were recruited as part of a larger prospective cohort in Cape Town, South Africa. The patients were treated with conventional therapy through the South African National Tuberculosis Program. Blood samples were collected at the time of diagnosis and after 2 and 4 weeks of treatment. At the end of the first treatment episode, all patients were classified as cured or treatment-complete. Those who experienced a second TB episode within 2 years of follow-up were classified as TB relapse or reinfection. The researchers used microarrays to compare gene expression in 10 patients who relapsed with patients who remained cured of their disease.
According to microarray data, there was a significant difference in the expression of 668 genes in the samples of patients who relapsed vs. those who achieved a lasting cure. The differences were sustained for a minimum of 4 weeks after treatment initiation. In addition, genes involved in the immune response were significantly overrepresented in relapsed patients. Further analysis suggested marked enrichment of genes involved in programmed cell death and apoptosis in patients who relapsed. The researchers confirmed these findings in a wider cohort through quantitative real-time PCR.
“Prediction of TB patients at risk of relapse after treatment completion would facilitate clinical management and enhance efficacy testing of new TB drugs, especially in early phase clinical trials,” the researchers concluded. – by Jen Byrne
- Reference:
- Cliff JM, et al. J Infect Dis. 2015;doi:10.1093/infdis/jiv447.
Disclosure: The researchers report no relevant financial disclosures.