Journal of Clinical Immunology · 5 authors, 1 centre
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This study examined neutrophils from patients with STAT1 gain-of-function (GOF) and chronic mucocutaneous candidiasis. It found that these neutrophils have a heightened pro-inflammatory state, including increased activation, degranulation, NETosis, and cytokine production, and this phenotype is not corrected by a JAK1/2 inhibitor.
This study investigated neutrophils from patients with STAT1 gain-of-function (GOF) and chronic mucocutaneous candidiasis (CMC). The authors demonstrate that STAT1 GOF neutrophils exhibit a pro-inflammatory phenotype with enhanced activation, degranulation, NETosis, and production of pro-inflammatory cytokines. They also report an increased interferon (IFN) signature. Treatment with the JAK1/2 inhibitor ruxolitinib had little effect on these neutrophil alterations. The study suggests these activated neutrophils may contribute to the autoimmune and vascular features of STAT1 GOF CMC. Limitations include a small, heterogeneous patient cohort and the inability to fully distinguish cell-intrinsic effects from the systemic pro-inflammatory environment.
