Overzealous immune response early in TB may signal risk of treatment failure

Chennai: People whose immune systems mount an unusually aggressive early response to tuberculosis may be less likely to respond well to standard drug treatment, suggests a new study from the ICMR National Institute for Tuberculosis Research. The researchers found that a group of immune proteins, known as the complement system, can serve as an early warning signal. A simple blood test measuring these proteins could help doctors identify such patients early and adjust therapy before the disease worsens, they concluded.
While more than 90% of people treated for TB recover with standard therapy, some show a poor response to the standard regimen. While reasons for failure vary, scientists delved into one of the causes related to the immune system.For research funded by the department of biotechnology and published in the peer-reviewed journal ‘Frontiers in Immunology', scientists tested blood samples from 68 patients whose pulmonary TB treatment did not go well and compared them with 108 TB patients who completed treatment. They found that body's defence mechanisms caused inflammation and destruction in some.Complement system is a group of proteins in the blood that "complements" antibodies and other defences by marking invaders such as bacteria and viruses for destruction, recruiting immune cells to the site, and sometimes directly punching holes in microbial membranes to kill them. "It's a group of proteins in the blood that acts like a back-up force for immune system. It helps the body find and destroy invaders," said senior diabetologist Dr Vijay Vishwanathan from MV Hospital for Diabetes. "When working properly, they help clear infections quickly. But if they become too active or stay switched on too long, they can cause harmful inflammation and damage healthy tissue." That is what happened to 68 patients in the study. At the start of treatment and after two months, patients with poor outcomes had higher levels of active complement components such as C3, C4b, C5, C5a, and a protein called C1q, and lower levels of natural "brakes" such as Factor H. The "brake" proteins that keep complement system in check are essential to maintain balance. "The findings suggest that early and sustained complement activation, particularly through classical pathway, is associated with adverse outcomes in TB," wrote the study's first author, Nathella Pavan Kumar. The study concluded that early blood tests for immune dysregulation could help doctors find patients at high risk of treatment failure, allowing for closer checks. The study, however, does not give an exact percentage of patients whose overactive immune system led to poor treatment outcomes.