ArticleThe Journal of clinical investigation2020
Inherited human IFN-γ deficiency underlies mycobacterial disease.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 3 of them syntheses that pooled it.
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Who cites it
92 citing papers in PubMed, 3 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Genetic, immunologic, and clinical features of 830 patients with Mendelian susceptibility to mycobacterial diseases (MSMD): A systematic review.The Journal of allergy and clinical immunology · 2024Pooled it
- An Updated Review on MSMD Research Globally and A Literature Review on the Molecular Findings, Clinical Manifestations, and Treatment Approaches in China.Frontiers in immunology · 2022Pooled it
- Successful Hematopoietic Stem Cell Transplantation in a Patient with Complete IFN-γ Receptor 2 Deficiency: a Case Report and Literature Review.Journal of clinical immunology · 2020Pooled it
- Mediastinal lymphadenitis caused by Mycobacterium avium complex in children: a rare case of airway compression.European journal of pediatrics · 2026Article
- Investigation of Cytokine Profiles, the Expression of Genes Involved in Somatic Hypermutation and Peripheral Tolerance, and Their Correlation with Autoantibody Levels in Northern-Thai Immunodeficient Patients Carrying Anti-Interferon-γ Autoantibodies.International journal of molecular sciences · 2026Article
- Human inherited RORγT deficiency encompasses genetic heterogeneity, T cell deficiency, and clinical homogeneity.medRxiv : the preprint server for health sciences · 2026Article
- A gE/gI/US9-triple deletion inactivated vaccine provides complete protection against emerging PRV variant infection.BMC veterinary research · 2026Article
- Adult Onset of MSMD Caused by IL-12Rβ1 Variants: Report of a Young Woman with NTM Infection Lacking Bacille Calmette-Guérin (BCG)-induced Diseases.Journal of clinical immunology · 2026Article
- Primary Immunodeficiency Diseases with BCG-Induced Diseases: A 15-Year Longitudinal Cohort Study.Journal of clinical immunology · 2026Article
- Targeting Tryptophan Metabolism for Tuberculosis Biomarkers and Host-Directed Therapy.The Journal of infectious diseases · 2026Review
- Ly6GeLife · 2026Article
- Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function.Nature immunology · 2026Article
- Mendelian susceptibility to mycobacterial disease: Clinical, immunological, and genetic study in India.Journal of human immunity · 2026Article
- Mendelian susceptibility to mycobacterial disease: IFN-γ-driven immunity collapse underlies heterogeneous infections.Frontiers in immunology · 2026Review
- Age-Related Patterns of Type II Interferon Immunity: Implications for Intramacrophagic Infections and MSMD Diagnosis During Childhood.Journal of clinical immunology · 2025Article
- Clinical recommendations for diagnosis and management of Mendelian susceptibility to mycobacterial disease in resource-limited settings.The journal of allergy and clinical immunology. Global · 2025Article
- Human genetics of Whipple's disease.Current opinion in rheumatology · 2025Review
- Decoding Immunobiology Through Genetic Errors of Immunity.Annual review of immunology · 2025Review
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome.EBioMedicine · 2025Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors at 13 institutions in 7 countries.
Funding
Abstract
Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by a selective predisposition to clinical disease caused by the Bacille Calmette-Guérin (BCG) vaccine and environmental mycobacteria. The known genetic etiologies of MSMD are inborn errors of IFN-γ immunity due to mutations of 15 genes controlling the production of or response to IFN-γ. Since the first MSMD-causing mutations were reported in 1996, biallelic mutations in the genes encoding IFN-γ receptor 1 (IFN-γR1) and IFN-γR2 have been reported in many patients of diverse ancestries. Surprisingly, mutations of the gene encoding the IFN-γ cytokine itself have not been reported, raising the remote possibility that there might be other agonists of the IFN-γ receptor. We describe 2 Lebanese cousins with MSMD, living in Kuwait, who are both homozygous for a small deletion within the IFNG gene (c.354_357del), causing a frameshift that generates a premature stop codon (p.T119Ifs4*). The mutant allele is loss of expression and loss of function. We also show that the patients' herpesvirus Saimiri-immortalized T lymphocytes did not produce IFN-γ, a phenotype that can be rescued by retrotransduction with WT IFNG cDNA. The blood T and NK lymphocytes from these patients also failed to produce and secrete detectable amounts of IFN-γ. Finally, we show that human IFNG has evolved under stronger negative selection than IFNGR1 or IFNGR2, suggesting that it is less tolerant to heterozygous deleterious mutations than IFNGR1 or IFNGR2. This may account for the rarity of patients with autosomal-recessive, complete IFN-γ deficiency relative to patients with complete IFN-γR1 and IFN-γR2 deficiencies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.