Impaired salivary gland activity in patients with autoimmune polyendocrine syndrome type I

Abstract

Autoimmune polyendocrine syndrome type I (APS-I) is a severe disease caused by mutations in the autoimmune regulator (AIRE) gene. We hypothesized that salivary gland dysfunction could be a possible unexplored component of these patients and here aimed to investigate salivary and lachrymal symptoms in the Norwegian cohort of APS-I patients (N = 41) and the aetiology behind it. Sicca symptoms and possible corresponding underlying factors were assessed by subjective reports combined with objective measures of saliva and tear flow, serological testing, immune fluorescence microscopy, ultrasonography and searching for putative autoantibodies in the salivary glands. In addition, defensin and anti-defensin levels were analysed in patients and compared with healthy controls. Our results indicate mild salivary and/or lachrymal gland dysfunction manifesting in low saliva or tear flow in a total of 62% of APS-I patients. Serum IgG from 9 of 12 patients bound to targets in salivary gland biopsy slides, although the specificity and pattern of binding varied. There was no reactivity against known Sjögren-associated autoantigens in sera from APS-I patients using quantitative methods, but 11% were ANA positive by immunofluorescence microscopy. We identified several putative autoantigens in one patient, although none of these were verified as APS-I specific. We conclude that impaired salivary gland activity is part of the clinical picture of APS-I and our findings could indicate an autoimmune aetiology. We further show that APS-I patients have an altered antimicrobial signature in both sera and saliva, which requires further investigations.

IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity

“…As one of the key functions of IL-22 is to induce AMP secretion from epithelial cells in concert with IL-17A, it is possible that the secretion of these natural antibiotics is impaired in APECED patients. However, previous work has not found decreased beta and alpha defensin concentrations in APECED saliva samples (52). Our study confirmed abundant, and not impaired, LCN2 levels in the saliva of APECED patients.…”

“…However, we think that neither factor had impact on our analysis as none of the study subjects received immunosuppressive drugs, and only one patient was on antifungals, all other medications were only hormone replacements. Moreover, objective sicca symptoms are rare in European APECED patients and were reportedly present only in patients over 33 years of age (52). Our study included relatively young patients (17.7 ± 10.9 years) and none of them reported dry mouth.…”

Profiling Autoantibodies against Salivary Proteins in Sicca Conditions

“…Another disease with sicca symptoms is autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a monogenic disorder caused by mutations in the AIRE transcription regulator leading to defective elimination of autoreactive T cells (Husebye et al 2018; Constantine and Lionakis 2019). Approximately 40% of APECED subjects exhibit SS-like sicca symptoms (designated here as APECED with sicca) by 30 y of age (Ferre et al 2016; Oftedal et al 2017). Consistent with autoimmune attack, immunofluorescence analysis revealed that 75% of APECED patients showed serum autoantibody immunoreactivity against the salivary gland (Oftedal et al 2017).…”

Oral microbiota in autoimmune polyendocrine syndrome type 1

“…Most APS-1 patients develop disease components affecting the oral cavity; enamel hypoplasia and CMC are both common manifestations [9,15]. Also a Sjögren’s-like syndrome without extractable nuclear antigen autoantibodies has recently been described [15,16]. These oral manifestations probably interfere with the homeostasis of the oral microbiota.…”