The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1
Authors' conclusion
Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results.
Study context
- Population
- Patients with APS-1 (autoimmune regulator (AIRE) deficiency) in a prospective natural history study; Aire-/- mice5 patients treated with ruxolitinib
- Outcome
- Interferon-γ responses in APS-1
Methodological detailsprospective natural history study, mouse models (Aire-/-Ifng-/-; Aire-/- treated with ruxolitinib), case series of ruxolitinib treatment
- Prospective natural history study
- Mouse models (Aire-/-Ifng-/-; Aire-/- treated with ruxolitinib)
- Case series of ruxolitinib treatment
Main finding
As reported in the abstract
- Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues
- Aire-/- mice: selectively increased interferon-γ production by T cells and enhanced interferon-γ, pSTAT1 and CXCL9 signals in multiple organs
- Ifng ablation or ruxolitinib JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and organ damage
Further findings
Ruxolitinib treatment of patients with APS-1
- Decreased T-cell-derived interferon-γ; normalized interferon-γ and CXCL9 levels
- Remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria and thyroiditis
- 5 patients
Safety
- No serious adverse effects from ruxolitinib were identified
- 5 patients
Original publication
The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1. N Engl J Med. Published 30 May 2024. doi:10.
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