Disseminated Mycobacterium avium Complex Infection in a Child with Partial Dominant Interferon Gamma Receptor 1 Deficiency in India

Abstract

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare condition characterized by clinical disease caused by weakly virulent mycobacteria. All genes mutated in MSMD patients are involved in IFN-γ immunity. Autosomal partial dominant (PD) interferon-γ receptor 1 (IFN-γR1) deficiency is the most frequent abnormality affecting the group of MSMD patients leading to impaired response of IFN-γ. We describe here a patient from India with disseminated infection due to Mycobacterium avium intracellulare (MAC) including multifocal osteomyelitis and BCG disease. A heterozygous mutation in exon 6 of IFNGR1 gene was identified, conferring an autosomal PD IFN-γR1 deficiency. Patient had recurrence of mycobacterial disease during antibiotic therapy for which subcutaneous IFN-γ was added as a modality of treatment for resistant MAC infection.

Mendelian susceptibility to mycobacterial disease: 2014–2018 update

“…Since the discovery of its first genetic etiology in 1996, MSMD has been reported and a causal genetic lesion described in 501 individuals from 356 kindreds originating from 57 countries on five continents (Figure a). Over this period, the genetic dissection of MSMD in these patients has revealed this condition to be caused by inborn errors of interferon (IFN)‐γ immunity . These findings confirm that IFN‐γ, first described in 1965 as an antiviral IFN, is actually the macrophage‐activating factor, as shown in 1983 .…”

Phosphorylation-Mediated IFN-γR2 Membrane Translocation Is Required to Activate Macrophage Innate Response

“…The left heatmap shown differentially expressed genes, the differentially expressed ISGs are shown on the right. IFN-gR2 is involved in IFN-g signaling via affecting dynamic receptor interactions with actin and lipid nanodomains (Blouin et al, 2016)$ Notably, abnormalities in IFN-gR1 and IFN-gR2 expression are closely associated with Mendelian susceptibility to mycobacterial disease (MSMD), a syndrome characterized by localized or disseminated infections caused by atypical mycobacteria (Sharma et al, 2015). Given the critical roles of IFN-gR2 in immunity and disease, understanding the mechanisms controlling translocation of IFN-gR2 from cytosol to membrane in immune cells such as macrophages has important biological significance and clinical implications.…”

Nontuberculous Mycobacterial Musculoskeletal Infection Cases from a Tertiary Referral Center, Colorado, USA

“…Previous case reports and series of NTM musculoskeletal infections have focused on the demographics, diagnosis, and treatment of patients with these difficult-to-manage infections (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Patients were often immunocompetent persons who contracted an NTM disease after direct inoculation via traumatic skin puncture (25)(26)(27)(28).…”