A novel patient with inherited TNF deficiency and tuberculosis

Inherited complete TNF deficiency in a previously healthy Iranian patient is linked to pulmonary and extrapulmonary tuberculosis onset between 10 and 15 years, with TNF p.Q225* abolishing TNF expression.

• Why it matters: TNF deficiency is known to predispose to tuberculosis, but reported phenotypes and ages of onset remain limited, especially across different genetic backgrounds. Clarifying human immune requirements for M. tuberculosis helps define which infections TNF controls.
• What they did: The team studied a patient with inherited complete TNF deficiency carrying the homozygous c.673C>T variant that creates the premature stop codon TNF p.Q225*. They assessed immune development and measured TNF secretion from primary leukocytes, and tested GM-CSF-derived macrophage respiratory burst.
• The result: TNF secretion was undetectable despite normal myeloid and lymphoid subset development, and macrophage respiratory burst was impaired, matching prior TNF-deficient Colombian cases. The case expands TB phenotype diversity and supports TNF as essential for immunity to Mycobacterium tuberculosis in humans, while appearing redundant for many other pathogens.

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