Radioligand-Binding Assay Reveals Distinct Autoantibody Preferences for Type I Interferons in APS I and Myasthenia Gravis Subgroups

Abstract

Patients with autoimmune polyendocrine syndrome type I (APS I) or acquired thymoma-associated myasthenia gravis (MG) surprisingly share several common features, including defective expression of the transcription factor AIRE and autoantibodies against type I interferons. Here, we have adapted and validated the radioligand-binding assay we recently developed against (35)S-Met-interferon-ω, for rapid and specific screening for autoantibodies against interferons-α2 and -α8. We then investigated their potential for diagnosis and for predicting clinical manifestations in patients with APS I and different subgroups of MG. Autoantibodies against interferons-ω, -α2, and -α8 occurred more often in patients with APS I (100%) and MG with thymoma (73%) than in late-onset MG (39%) and early-onset MG (5%). These autoantibodies showed preferences for interferon-ω in APS I and for the interferon-αs in MG, hinting at thymic aberrations in both groups. The exact profile of type I interferon antibodies may indicate MG subtype and may hint at thymoma recurrence.

Identification of autoimmune polyendocrine syndrome type 1 in patients with isolated hypoparathyroidism

“…Sequencing identified two heterozygous mutations in this patient. IFN‐ω and IFN‐α antibodies were detected in isolated cases of PAI in two other studies . AIRE mutations were either absent or not studied in these patients.…”

“…IFN-x and IFN-a antibodies were detected in isolated cases of PAI in two other studies. 35,36 AIRE mutations were either absent 35 or not studied 36 in these patients.…”

Expression of the Autoimmune Regulator Gene and Its Relevance to the Mechanisms of Central and Peripheral Tolerance

“…In a further study, the same research group, utilizing a radioligand-binding assay, confirmed that Abs to IFN- ω occur in the totality of APS-1 patients and beat the prevalence of Abs to two subtypes of IFN- α , namely IFN- α 2 and IFN- α 8 , that in turn are found in a high percentage of patients with thymoma-associated myasthenia gravis [84]. …”

Early‐onset hypoparathyroidism and chronic keratitis revealing APECED

“…The first disease components, most usually chronic mucocutaneous candidiasis and hypoparathyroidism, normally emerge in childhood, but the heterogeneity of APECED in terms of its initial clinical presentation can make it challenging to identify and, typically, the condition is diagnosed after the first decade of life 1 , 5 . More recently, the presence of antibodies against interferon (IFN)- ω and IFN- α 2 has been shown to aid diagnosis due to their sensitivity and relative specificity for APECED 6 , 7 . Anti-interleukin (IL)-22, anti-IL-17A, and anti-IL-17F antibodies are also common 8 .…”