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

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.

The mtDNA replication-related genes TFAM and POLG are associated with leprosy in Han Chinese from Southwest China

“…All the tag SNPs were in HWE in both controls and cases (Table S2). The observed distributions of allele and genotype frequencies in leprosy patients and controls were summarized in Tables 1 and S3, Recently, Gaschignard and colleagues performed association study using leprosy clinical forms as phenotypes (MB and PB) and they found that this is a powerful strategy to identify genetic factors affecting disease polarization [41]. However, we found no association of TFAM and POLG SNPs with disease polarization when we compared MB patients with PB patients (Tables 1, S3 and S4).…”

Leucine Rich Repeat Kinase 2 and Innate Immunity

“…Leucine-rich repeat kinase 2 has also been genetically linked to Leprosy, a chronic dermato-neurological disorder caused by long-term infection with Mycobacterium leprae. Based on the clinical symptomology resulting from bacterial load and individual immune responses, leprosy acts as a spectrum of disease ranging from paucibacillary to multibacillary subtypes (Gaschignard et al, 2016). GWAS analysis of a Han Chinese cohort first suggested an association of LRRK2 rs1873613 with Leprosy per se, and in particular a significant association of LRRK2 rs1491938 with the multibacillary form of leprosy (Zhang F. R. et al, 2009).…”

Reanalysis And Integration Of Public Microarray Datasets Reveals Novel Host Genes Modulated In Leprosy

“…Despite the effectiveness of treatment, transmission likely occurs prior to diagnosis since it is primarily detected based solely on clinical findings. As yet there is no gold standard method to differentiate asymptomatic infection from disease, and early detection and unambiguous diagnosis is incredibly difficult [5][6][7][8]. As exposure to the etiological agent is not sufficient to develop the disease [9], it is assumed that early diagnosis is key in controlling the disease transmission, along with chemo-and immunoprophylactic strategies for high risk individuals, such as household contacts [10].…”