Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.

Autor:	Paldino G; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Faienza MF; Department of Precision and Regenerative Medicine and Ionian Area, University of Bari 'Aldo Moro', Bari, Italy., Cappa M; Research Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Pietrobattista A; Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Capalbo D; Pediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, Italy., Valenzise M; Department of Human Pathology of Adulthood and Childhood, Messina University, Messina, Italy., Lampasona V; San Raffaele Hospital, IRCCS, Milan, Italy., Cudini A; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Carbone E; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Pagliarosi O; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Maggiore G; Hepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy., Salerno M; Pediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy., Betterle C; Clinical Immunology, Padua University, Padua, Italy., Fierabracci A; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Jun 30; Vol. 14, pp. 1172369. Date of Electronic Publication: 2023 Jun 30 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1172369
Abstrakt:	Introduction: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). Patients and Methods: We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Results: Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Conclusion: Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Paldino, Faienza, Cappa, Pietrobattista, Capalbo, Valenzise, Lampasona, Cudini, Carbone, Pagliarosi, Maggiore, Salerno, Betterle and Fierabracci.)
Databáze:	MEDLINE
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