Clinical features of dominant and recessive interferon gamma receptor 1 deficiencies

Lancet. 2004 Dec;364(9451):2113-21. doi: 10.1016/S0140-6736(04)17552-1.


Background: Interferon gamma receptor 1 (IFNgammaR1) deficiency is a primary immunodeficiency with allelic dominant and recessive mutations characterised clinically by severe infections with mycobacteria. We aimed to compare the clinical features of recessive and dominant IFNgammaR1 deficiencies.

Methods: We obtained data from a large cohort of patients worldwide. We assessed these people by medical histories, records, and genetic and immunological studies. Data were abstracted onto a standard form.

Findings: We identified 22 patients with recessive complete IFNgammaR1 deficiency and 38 with dominant partial deficiency. BCG and environmental mycobacteria were the most frequent pathogens. In recessive patients, 17 (77%) had environmental mycobacterial disease and all nine BCG-vaccinated patients had BCG disease. In dominant patients, 30 (79%) had environmental mycobacterial disease and 11 (73%) of 15 BCG-vaccinated patients had BCG disease. Compared with dominant patients, those with recessive deficiency were younger at onset of first environmental mycobacterial disease (mean 3.1 years [SD 2.5] vs 13.4 years [14.3], p=0.001), had more mycobacterial disease episodes (19 vs 8 per 100 person-years of observation, p=0.0001), had more severe mycobacterial disease (mean number of organs infected by Mycobacterium avium complex 4.1 [SD 0.8] vs 2.0 [1.1], p=0.004), had shorter mean disease-free intervals (1.6 years [SD 1.4] vs 7.2 years [7.6], p<0.0001), and lower Kaplan-Meier survival probability (p<0.0001). M avium complex osteomyelitis was more frequent in dominant than in recessive patients (22/28 [79%] vs 1/8 [13%], p=0.002), and this disorder without other organ involvement arose only in dominant patients (9/28 [32%]). Disease caused by rapidly growing mycobacteria was present in more recessive than dominant patients (7/22 [32%] vs 1/38 [3%], p=0.002).

Interpretation: Recessive complete and dominant partial IFNgammaR1 deficiencies have related clinical phenotypes, but are distinguishable by age at onset, dissemination, and clinical course of mycobacterial diseases. A strong correlation exists between IFNGR1 genotype, cellular responsiveness to interferon gamma, and clinical disease features.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BCG Vaccine
  • Female
  • Genes, Dominant
  • Genes, Recessive
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Interferon gamma Receptor
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation
  • Male
  • Mutation
  • Mycobacterium Infections, Nontuberculous / genetics
  • Mycobacterium Infections, Nontuberculous / immunology
  • Phenotype
  • Receptors, Interferon / deficiency*
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Sequence Analysis, DNA
  • Tuberculosis / prevention & control
  • Tumor Necrosis Factor-alpha / biosynthesis


  • BCG Vaccine
  • Receptors, Interferon
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma