INTERFERON GAMMA RECEPTOR 1 DEFICIENCY (IFNGR1) WITH NEGATIVE QUANTIFERON GOLD AND ELEVATED C-REACTIVE PROTEIN

Abstract

Introduction Defects in IFNGR1 leads to Mendelian Susceptibility to Mycobacterial Disease. The extent of reduction of IFNGR1 determines the phenotype of disease expression. Mutations occurring in Autosomal Dominant IFNGR1 deficiency lead to non-functional receptors on cell surfaces which fail to transduce IFNG signals. These patients are older than those with Autosomal Recessive complete IFGR1 deficiency, with later onset, less severe mycobacteria infections but high prevalence (79%) of non-tuberculous mycobacterial (NTM) osteomyelitis. Case Description A 30-year old male from United Arab Emirates presented with recurrent atypical mycobacteria infections for over 20 years, having multiple courses of anti-TB therapy. Therapy with IFNG from 2009 to 2011 was discontinued due to adverse effects. Gene sequencing identified a pathogenic variant in the IFNGR1 gene in a heterozygous state at c.819_822del p.(Asn274Hisfs*2) creating a shift in the reading frame starting at codon 274, with the new reading frame ending in a stop codon 2 position downstream causing autosomal dominant (AD) immunodeficiency type 27B mycobacteriosis. His QuantiFERON Gold test was negative despite the history of TB. C-reactive protein (CRP) was elevated at 74.6. His CD4, CD8 and CD3 absolute counts were normal. MRI scan of the thoracic spine showed multifocal areas of thoracic vertebral marrow infiltration. Discussion AD IFNGR1 deficiency leads often to NTM osteomyelitis as suspected in this case. Neither CRP elevation nor accuracy of the QuantiFERON Gold test have been reported in AD IFNGR1 deficiency patients. This case suggests QuantiFERON Gold test performance may be impaired in these patients.