Leprosy and immunity: genetics and immune function in multiple case families

Area of Science:

• Immunogenetics
• Medical Genetics
• Infectious Diseases

Background:

• Leprosy, caused by Mycobacterium leprae, exhibits variable clinical manifestations.
• Genetic factors are suspected to play a role in leprosy susceptibility and disease type.
• Previous studies have investigated associations between human leucocyte antigen (HLA) and leprosy.

Purpose of the Study:

• To investigate genetic susceptibility to Mycobacterium leprae infection in Australian Aboriginal families.
• To identify potential genetic linkages with leprosy phenotypes, including clinical leprosy, subtype, and immune response.
• To explore the role of HLA and non-HLA genes in leprosy.

Main Methods:

• Studied 10 multi-case leprosy families comprising 87 individuals.
• Assessed M. leprae exposure using ELISA and indirect immunofluorescence antibody assay.
• Evaluated T cell function via lymphocyte proliferation assays (LMAT, LTT) and leucocyte migration inhibition factor (LIF) production.
• Analyzed genetic linkage with HLA and non-HLA markers.

Main Results:

• 78% of individuals without clinical leprosy showed evidence of M. leprae exposure.
• In vitro T cell function assays were less reliable indicators of exposure compared to antibody detection.
• No direct association was found between specific HLA or non-HLA genes and clinical leprosy or subtype.
• A significant linkage was suggested between HLA haplotype and lack of LIF production (non-responsiveness to M. leprae).

Conclusions:

• A gene on chromosome 6, closely linked to the HLA haplotype, may control non-responsiveness to M. leprae.
• This gene appears to follow autosomal recessive inheritance with high penetrance.
• Genetic control may be more influential on leprosy disease type (lepromatous leprosy) than initial susceptibility.
• The major histocompatibility gene complex region is implicated in leprosy pathogenesis.