02320nas a2200205 4500000000100000008004100001653001900042653001200061653001500073653001500088653001200103653002400115100001200139700001100151700000900162700001000171245009400181520182600275022001302101 2016 d10aSusceptibility10aleprosy10aAutoimmune10aEnrichment10aNetwork10aSusceptibility gene1 aZhang D1 aWang D1 aLi Y1 aYao Y00aIntegrative analyses of leprosy susceptibility genes indicate a common autoimmune profile3 a

Background

Leprosy is an ancient chronic infection in the skin and peripheral nerves caused by Mycobacterium leprae. The development of leprosy depends on genetic background and the immune status of the host. However, there is no systematic view focusing on the biological pathways, interaction networks and overall expression pattern of leprosy-related immune and genetic factors.

Objectives

To identify the hub genes in the center of leprosy genetic network and to provide an insight into immune and genetic factors contributing to leprosy.

Methods

We retrieved all reported leprosy-related genes and performed integrative analyses covering gene expression profiling, pathway analysis, protein–protein interaction network, and evolutionary analyses.

Results

A list of 123 differentially expressed leprosy related genes, which were enriched in activation and regulation of immune response, was obtained in our analyses. Cross-disorder analysis showed that the list of leprosy susceptibility genes was largely shared by typical autoimmune diseases such as lupus erythematosus and arthritis, suggesting that similar pathways might be affected in leprosy and autoimmune diseases. Protein–protein interaction (PPI) and positive selection analyses revealed a co-evolution network of leprosy risk genes.

Conclusions

Our analyses showed that leprosy associated genes constituted a co-evolution network and might undergo positive selection driven by M. leprae. We suggested that leprosy may be a kind of autoimmune disease and the development of leprosy is a matter of defect or over-activation of body immunity.

 

 

 

 

 

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