A novel patient with inherited TNF deficiency and tuberculosis
Two otherwise healthy patients from Colombia, now aged 30 and 38 years, developed pulmonary tuberculosis due to inherited, complete TNF deficiency at the ages of 19 and 18 years. We report here a previously healthy Iranian patient with inherited complete TNF deficiency who was diagnosed with both pulmonary and extrapulmonary TB between 10 and 15 years of age. The homozygous TNF variant (c.673C>T) introduces a premature stop codon (TNF p.Q225*) resulting in losses of expression and function. Despite normal myeloid and lymphoid subset development, the patient's primary leukocytes do not secrete detectable amounts of TNF. As in the TNF-deficient Colombian patients, the respiratory burst of GM-CSF-derived macrophages is impaired. Our findings expand the spectrum of TB phenotypes in patients with TNF deficiency and confirm that TNF is essential for immunity to M. tuberculosis in humans but apparently redundant against many other pathogens, including weakly virulent mycobacteria.
Authors
- Abdollah Karimi (ORCID: https://orcid.org/0000-0003-4599-1496)
- Camille Soudée (ORCID: https://orcid.org/0009-0002-1445-7223)
- Aurélie Cobat (ORCID: https://orcid.org/0000-0001-7209-6257)
- Narelle Keating (ORCID: https://orcid.org/0000-0002-4392-0806)
- Candice Lainé (ORCID: https://orcid.org/0000-0003-3258-6969)
- Mehrnaz Mesdaghi (ORCID: https://orcid.org/0000-0001-7951-0967)
- Abbas Solgi
- Jérémie Rosain (ORCID: https://orcid.org/0000-0002-2822-161X)
- Mélanie Migaud (ORCID: https://orcid.org/0000-0003-3062-1214)
- Vincent Meynier (ORCID: https://orcid.org/0000-0002-7204-7495)
- Samin Sharafian (ORCID: https://orcid.org/0000-0002-2037-0274)
- Yoann Seeleuthner (ORCID: https://orcid.org/0000-0002-1878-8567)
- Vivien Béziat (ORCID: https://orcid.org/0000-0002-4020-824X)
- Stéphanie Boisson‐Dupuis (ORCID: https://orcid.org/0000-0002-7115-116X)
- Zahra Chavoshzadeh (ORCID: https://orcid.org/0000-0003-1869-8630)
- Mohammad Saberi (ORCID: https://orcid.org/0000-0001-8431-395X)
- Jean-Laurent Casanova (ORCID: https://orcid.org/0000-0002-7782-4169)
- Sinem Ünal (ORCID: https://orcid.org/0009-0002-5460-5948)
- Laurent Abel
- Jacinta Bustamante
- Anne-Sophie LHonneur
Institutions
- Inserm (FR)
- Hôpital Cochin (FR)
- Human Genetic of Infectious Diseases (FR)
- Institut des Maladies Génétiques Imagine (FR)
- Shahid Beheshti University of Medical Sciences (IR)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- medRxiv
- Published
- 2026-11-09
- DOI
- https://doi.org/10.64898/2026.11.09.26366865
- Primary Topic
- Immunodeficiency and Autoimmune Disorders
- Type
- preprint