Mimicking B and T cell epitopes between Mycobacterium leprae and host as predictive biomarkers in type 1 reaction in leprosy

Vinay Kumar Pathak,Shoor Vir Singh,Utpal Sengupta,Itu Singh

doi:10.1038/s41598-021-04135-5

Abstract

Several Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host. Presence of autoantibodies like, rheumatoid factor, anti-nuclear factor and antibodies to host, collagen, keratin, myelin basic protein (MBP) and myosin, have been earlier reported in leprosy patients. In the present study, we detected the role of mimicking epitopes between Mycobacterium leprae and host components in the induction of autoimmune response in leprosy. Based on our previous findings, we predicted and synthesized a total of 15 mimicking linear B cell epitopes (BCE) and 9 mimicking linear T cell epitopes (TCE) of keratin and MBP. Humoral and cell-mediated immune responses against these epitopes were investigated in Non-reaction (NR), Type 1 reaction (T1R) leprosy patients, and healthy controls. We observed significantly higher levels of antibodies against 8 BCE in T1R in comparison to NR leprosy patients. Further, we also found 5 TCE significantly associated with lymphocyte proliferation in the T1R group. Our results indicated that these epitopes play a key role in the induction of autoimmune response in leprosy and are also strongly associated with the inflammatory episodes of T1R. Conclusively, these molecules may be employed as a biomarker to predict the inflammatory episodes of T1R.

Highlights

Several Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host
The humoral immune response against each mimicking B cell epitope of keratin and myelin basic protein was estimated by the level of auto antibodies
Antibodies against HSP1, HSP2, HSP3 were found to be higher in NR when compared to Type 1 reaction (T1R); the mean level of antibodies against HSP1 was found to be significantly higher in both T1R and NR when compared to HC (p < 0.0001)

Summary

Introduction

Several Mycobacterial infections including leprosy and tuberculosis are known to evoke autoimmune responses by modulating homeostatic mechanism of the host. We detected the role of mimicking epitopes between Mycobacterium leprae and host components in the induction of autoimmune response in leprosy. Our results indicated that these epitopes play a key role in the induction of autoimmune response in leprosy and are strongly associated with the inflammatory episodes of T1R These molecules may be employed as a biomarker to predict the inflammatory episodes of T1R. The immune response is characteristic of delayed type hypersensitivity (DTH) reaction with an influx of peripheral blood lymphocytes demonstrating an increased reactivity to M. leprae antigens in a lymphocyte transformation test (LTT)[4] This may lead to a local decrease in bacillary load and augmentation of T cell reactivity in the affected nerve leading to nerve damage[5].

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