STAT3 gain-of-function mutation in a patient with pulmonary infection.

Background: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor involved in cellular proliferation, apoptosis, and differentiation. Mutations in the STAT3 gene have been associated with dysregulation of the immune system giving rise to primary immunodeficiency syndromes (PID). Clinically, patients may present with very broad manifestations, and its diagnosis is usually very challenging. Proper treatment remains unclear, and limited options are available.

Methods: We report an adult male patient with long-standing history of immunodeficiency, who was found to have infection. Two-hundred and seven immunogenes were sequenced using next-generation sequencing technology (NGS).

Results: A STAT3 heterozygous missense pathologic variant was identified in the patient located in the transactivation domain (TA) of STAT3, associated with a gain of functionality, leading to recurrent bronchopulmonary infections, and involvement of multiple organ systems.

Conclusions: Severe cases of autoimmunity should prompt for evaluation of PIDs in the setting of genetic mutations. Anti-IL-6 therapy may benefit patients with STAT3 GOF mutations. These patients should also be screened for lymphoproliferative disorders.