Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load

Background Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. Methodology/Principal findings 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark’s microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. Conclusions/Significance We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.
Author summary Leprosy, which has been reported throughout human history since Biblical times, still presents unclear aspects in regards to its pathogeny, and represents a public health concern, particularly in developing countries, where poor sanitary conditions of socially disfavored groups is a relevant contributing factor in maintaining disease dissemination. Although its signs and symptoms are primarily found in young adults, the increasing number of elderly individuals with leprosy is a recent phenomenon that requires clarification. Considering the specific biochemical profile of the elderly, as well as the influence thereof on their immune response to infection, this work demonstrates that elderly leprosy patients present increased levels of oxidative damage in blood and skin lesions when compared to younger patients. Such findings appear to be correlated with low gene expression of antioxidant enzymes, particularly among multibacillary patients. This work intends to contribute to a better understanding on the progress of leprosy in elderly groups.