A novel patient with inherited TNF deficiency and tuberculosis
Year: 2026
Type: preprint
Abstract: 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.
Source: medRxiv
Authors: Narelle Keating, Mehrnaz Mesdaghi, Zahra Chavoshzadeh, Abdollah Karimi, Mohammad Saberi, Sinem Unal, Vincent Meynier, Camille Soudee, Candice Laine, Abbas Solgi, Samin Sharafian, Anne-Sophie LHonneur, Melanie Migaud, Yoann Seeleuthner, Aurelie Cobat, Laurent Abel, Vivien Beziat, Jeremie Rosain, Jacinta Bustamante, Jean-Laurent Casanova, Stephanie Boisson-Dupuis
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225658749
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