Long-term follow-up of autoimmune polyendocrine syndrome type 1 in Norway

*AIRE* biallelic variants (classical) or dominant-negative variants (non-classical) with dysregulated IFN cytokine signature

A longitudinal analysis of 71 APS-1 patients (49 classical, 22 non-classical) followed from 1996 to 2025 in the Norwegian Registry of Organ-specific Autoimmune Diseases characterizes clinical and molecular profiles by AIRE genotype. The most frequent classical manifestations were chronic mucocutaneous candidiasis, enamel hypoplasia, and primary adrenal insufficiency (PAI); non-classical forms presented with vitiligo, hypothyroidism, and PAI. A broad proinflammatory cytokine signature and elevated soluble IFN-α/β receptor levels were observed in classical forms. The authors recommend considering APS-1 in any PAI diagnosed before age 20 and performing AIRE sequencing.

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This 30-year follow-up is valuable for understanding the natural history of APS-1, often diagnosed late. The recommendation to sequence AIRE in any patient with early PAI is pragmatic and applicable in genetic endocrinology consultation. The dysregulated IFN signature could open targeted therapeutic avenues.