title: 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.
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, INSERM, Paris, France, EU.|Paris Descartes University, Imagine Institute, Paris, France, EU.
authors.forename: Jean
authors.initials: J
authors.lastname: Gaschignard
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, INSERM, Paris, France, EU.|Paris Descartes University, Imagine Institute, Paris, France, EU.|Unité de Génétique fonctionnelle des maladies infectieuses, Institut Pasteur, Paris, France, EU.
authors.forename: Audrey Virginia
authors.initials: AV
authors.lastname: Grant
authors.affiliation: Hospital for Dermato-Venerology, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Van
authors.initials: NV
authors.lastname: Thuc
authors.affiliation: Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Marianna
authors.initials: M
authors.lastname: Orlova
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, INSERM, Paris, France, EU.|Paris Descartes University, Imagine Institute, Paris, France, EU.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cobat
authors.affiliation: Hospital for Dermato-Venerology, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Thu
authors.initials: NT
authors.lastname: Huong
authors.affiliation: Hospital for Dermato-Venerology, Ho Chi Minh City, Vietnam.
authors.forename: Nguyen Ngoc
authors.initials: NN
authors.lastname: Ba
authors.affiliation: Hospital for Dermato-Venerology, Ho Chi Minh City, Vietnam.
authors.forename: Vu Hong
authors.initials: VH
authors.lastname: Thai
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, INSERM, Paris, France, EU.|Paris Descartes University, Imagine Institute, Paris, France, EU.
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.affiliation: Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|The McGill International TB Centre, Departments of Human Genetics and Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
authors.affiliation: Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, INSERM, Paris, France, EU.|Paris Descartes University, Imagine Institute, Paris, France, EU.|URC, CIC, Necker and Cochin Hospitals, Paris, France, EU.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Alcaïs
mesh_terms: D000483:Alleles; D000818:Animals; D001135:Armadillos / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D056006:Leprosy, Multibacillary / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D056005:Leprosy, Paucibacillary / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D008297:Male; D009166:Mycobacterium leprae / Q000502:physiology; D058069:Neglected Diseases / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology