Finding Leprosy Biomarkers May Lead to Advances in Other Infectious Diseases

A study in BMC Infectious Diseases suggests possible biomarkers for flare-up of leprosy that may also have application to how other chronic infectious diseases are treated.

Leprosy is a chronic, immunoregulatory infectious disease caused by Mycobacterium leprae that particularly affects the skin and peripheral nerves and often results in severe, life-long disabilities and deformities. While the incidence of leprosy has plateaued worldwide, the condition remains endemic in Africa, South America, and Asia, and new cases are often detected in developed countries, where it is often misdiagnosed.

Acute inflammatory reactions such as those associated with leprosy are a frequently occurring, tissue destructing phenomenon in infectious- as well as autoimmune diseases, providing clinical challenges for early diagnosis. For leprosy, in particular, early lab tests that would lead to early diagnosis and early prevention of tissue damage are not available. Thus, identifying biomarkers would be of great utility in diagnostic and treatment efforts.

In the current study, the researchers examined prospective cohorts including leprosy patients with and without reactions in Bangladesh, Brazil, Ethiopia and Nepal. The presence of multiple cyto-/chemokines induced by M. leprae antigen stimulation of peripheral blood mononuclear cells as well as the levels of antibodies directed against M. leprae-specific antigens in sera, were measured longitudinally in patients.

At all sites, longitudinal analyses showed that IFN-γ-, IP-10-, IL-17- and VEGF- production by M. leprae (antigen)-stimulated peripheral blood mononuclear cells peaked at diagnosis of type 1 reactions, compared to when reactions were absent. “In contrast, IL-10 production decreased during type 1 reaction while increasing after treatment,” the study authors noted. “Thus, ratios of these pro-inflammatory cytokines versus IL-10 provide useful tools for early diagnosing type 1 reactions and evaluating treatment. Of further importance for rapid diagnosis, circulating IP-10 in sera were significantly increased during type 1 reactions. On the other hand, humoral immunity, characterized by M. leprae-specific antibody detection, did not identify onset of type 1 reactions, but allowed treatment monitoring instead.”

The researchers observed that there is translational importance to other infectious diseases, because similar intra-individual trends were observed for development of Reversal reaction/ type 1 reaction (RR) in different endemic areas, allowing global application of these biomarkers in tests for early diagnosis of RR. “The biomarker profiles identified in this study for RR can... provide an approach for other chronic diseases with acute inflammatory states such as tuberculosis and buruli ulcer (paradoxical reactions) and Crohn’s disease to help early diagnose such episodes thereby contributing to timely treatment and prevention of disease-specific tissue damage.”