Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases.

Jean Gaschignard,Erwin Schurr,Laurent Abel,Marianna Orlova,Nguyen Ngoc Ba,Audrey Virginia Grant,Nguyen Thu Huong,Aurélie Cobat,Nguyen Van Thuc,Vu Hong Thai,Alexandre Alcaïs,Christian Johnson

doi:10.1371/journal.pntd.0004345

Abstract

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes.Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy.

Highlights

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, with over 200,000 new cases detected each year, often leading to severe disabilities and social stigma
From the early observations of familial aggregation of leprosy cases to the most recent genome-wide association studies identifying genetic polymorphisms associated with leprosy, there is strong evidence that the development of the disease is under tight human genetic control [1,2]
Leprosy has long been a major focus of investigation for immunologists because it is an excellent example in natura of the clinical impact of a differential immune response of B and T lymphocytes on the form of disease, but it has not been thoroughly considered by geneticists

Summary

Introduction

Leprosy is a chronic infectious disease caused by Mycobacterium leprae, with over 200,000 new cases detected each year, often leading to severe disabilities and social stigma. The tuberculoid form is characterized by a small number of hypopigmented, well-bordered, anesthetic skin lesions with a low bacillary load ( this form is commonly referred to as “paucibacillary” [PB]), early peripheral nerve impairment, and a T-helper 1 (Th1)–mediated immune response. Leprosy has long been a major focus of investigation for immunologists because it is an excellent example in natura of the clinical impact of a differential immune response of B and T lymphocytes on the form of disease, but it has not been thoroughly considered by geneticists. Polarization can be regarded as a neglected phenotype To address this shortcoming, we have conducted a review of epidemiological studies addressing leprosy subtypes and polarization. We provide suggestions for future research on PB and MB leprosy and propose that the use of the armadillo model will be of pivotal importance for the study of these phenotypes

Review of the literature

Results and Discussion

Conclusion