Paradox of autoantibodies and immune deficiency: Interferon gamma antibodies and susceptibility to intracellular pathogens

© 2015 Indian Journal of Medical Microbiology Published by Wolters Kluwer Medknow Genetic defect of IFNG receptor results in reduced production of TNF alpha and other pro‐inflammatory cytokines in response to IFNG and endotoxin, defective MHC Class II expression in response to specific stimulation and poor presentation of antigen to T-cells.[6] These findings were later corroborated in IFNG R1 knockout mice which showed a marked susceptibility to challenge with mycobacteria with failure to develop mature granulomas and protective immunity. The significance of IFNG pathways has been elegantly demonstrated in mice with targeted disruptions of other related genes also.[9] In fact IFNG and IL-12 pathway defects lead to the Mendelian susceptibility to mycobacterial diseases (MSMD); there are more than 12 genes[15] upstream and downstream along STAT 1/TYK2/ JAK1, 2 pathways [Figure 1] which if mutated, result in MSMD (OMIM 209950). India has a large reservoir of mycobacterial TB (MTB) patients and it is highly likely that some of these patients might carry Mendelian susceptibility to mycobacterial infections.