Persistently Increased Anti-cytokine Antibodies Without Clinical Disease in a Boy with APS1 Genotype

Excerpt

In patients with autoimmune polyendocrine syndrome type 1 (APS1), chronic mucocutaneous candidiasis (CMC) is usually the earliest and most common clinical feature, especially in those homozygous for the c.769C > T “Finnish” allele (R257X) [1]. Notably, ~ 100% of APS1 patients have high titer IgG autoantibodies (autoAbs) that neutralize type I interferons, especially IFN-\(\upomega\) and IFN-\({\alpha }\) subtypes [1, 2]. Though rare in other conditions, these autoAbs were further implicated recently by their ~ 10% prevalence in 987 other cases with severe coronavirus disease (Bastard et al., Science, 2020). These autoAbs against type I interferons have proved to be early and highly reliable diagnostic markers for APS1, regardless of the exact clinical picture or autoimmune regulator gene (AIRE) mutation [3]. However, there are conflicting reports about the relative contributions of altered TH17/TH22 function and IL17A/F and IL-22 autoAbs to the CMC. The absence of CMC in one rare unaffected sibling “S1”—despite high levels of IL-17F and IL-22 autoAbs—is intriguing [2, 4]. On the other hand, IL-22-neutralizing antibodies appeared to be pathogenic in a mouse model of oropharyngeal candidiasis, when their transfer led to delayed clearance of yeasts from the oral cavity [5]. …