Partial interferon-γ receptor deficiency and non-tuberculous mycobacterial lung disease

SummaryInterferon-γ (IFN-γ) plays a key role in the host defense response against mycobacterial disease, and a complete or partial deficiency in IFN-γ receptor 1 (IFN-γR1) or IFN-γ receptor 2 (IFN-γR2) has been reported to contribute to susceptibility to disseminated infection with non-tuberculous mycobacteria (NTM). However, IFN-γR1 and IFN-γR2 deficiencies have not yet been studied in adult patients with isolated NTM lung disease. The purpose of the present study was to evaluate whether partial IFN-γR1 and IFN-γR2 deficiency are associated with human susceptibility to NTM lung disease. We studied 40 patients with NTM lung disease (Mycobacterium avium complex infection, 20 patients; Mycobacterium abscessus infection, 20 patients) for partial IFN-γR1 and IFN-γR2 deficiency. Genomic DNA was amplified by polymerase chain reaction and sequenced for revealing mutations of the IFN-γR1 and IFN-γR2 gene. None of the patients had previously reported homozygous recessive missense mutation causing an amino-acid substitution in the extracellular domain of the receptor (I87T) and hotspot for small deletions (818delT, 818del4) of the IFN-γR1 or homozygous missense mutation (R114C) of the IFN-γR2. In conclusion, in adult patients with isolated NTM lung disease, there is no evidence for previously known genetic defects of partial deficiencies of IFN-γR1 and IFN-γR2 to correlate with disease.