The following is a summary of “Ruxolitinib Treatment Ameliorates Clinical, Immunological, and Transcriptomic Aberrations in Patients with STAT3 Gain-of-Function Disease,” published in the December 2024 issue of Allergy and Immunology by Catak et al.
STAT3 gain-of-function (GOF) disease causes lymphoproliferation, autoimmunity, and failure to thrive. JAK inhibitors relieve symptoms, but their effect on pathogenesis is unclear.
Researchers conducted a retrospective study to investigate the clinical, immunological, and transcriptomic responses of 4 patients with STAT3 GOF under long-term ruxolitinib treatment.
They conducted clinical and immunological evaluations at baseline and after 3, 8, 12, and over 12 months of ruxolitinib treatment. Assessments included circulating T follicular helper cells (cT FH ), regulatory T (Treg) cells, cytokine levels, proliferation assays, and transcriptomic changes. T-cell receptor sequencing was also performed.
The results showed ruxolitinib controlled clinical manifestations and increased naive CD4+ and CD8+ T cell populations while reducing effector memory T cells. cT FH and double-negative T cells also decreased, and Treg cell percentages further declined. Cytokine production of IFN-γ, IL-17A, IL-10, and IL-4 remained unchanged in CD4+ T cells. Treatment normalized the transcriptome in peripheral blood mononuclear cells, with significant downregulation of STAT3 -targeted, interferon-related, myeloid activation, and cytotoxic CD8+ T-cell genes, lasting up to 12 months. TCR analysis identified potential auto-reactive T cell clones.
They found that ruxolitinib reversed cellular and transcriptomic abnormalities, improving understanding of the disease. Key immunological markers were identified for precise monitoring.
Source: jacionline.org/article/S0091-6749(24)01284-3/abstract
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