Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies
IntroductionAutoimmune 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...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172369/full |
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| author | Giorgia Paldino Maria Felicia Faienza Marco Cappa Andrea Pietrobattista Donatella Capalbo Mariella Valenzise Vito Lampasona Annamaria Cudini Elena Carbone Olivia Pagliarosi Giuseppe Maggiore Mariacarolina Salerno Corrado Betterle Alessandra Fierabracci |
| author_facet | Giorgia Paldino Maria Felicia Faienza Marco Cappa Andrea Pietrobattista Donatella Capalbo Mariella Valenzise Vito Lampasona Annamaria Cudini Elena Carbone Olivia Pagliarosi Giuseppe Maggiore Mariacarolina Salerno Corrado Betterle Alessandra Fierabracci |
| author_sort | Giorgia Paldino |
| collection | DOAJ |
| description | IntroductionAutoimmune 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 methodsWe 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.ResultsBased 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.ConclusionAlthough 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. |
| first_indexed | 2024-03-13T02:15:01Z |
| format | Article |
| id | doaj.art-788c085f8c4a4b618a838e8a8115d94b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T02:15:01Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-788c085f8c4a4b618a838e8a8115d94b2023-06-30T16:39:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11723691172369Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathiesGiorgia Paldino0Maria Felicia Faienza1Marco Cappa2Andrea Pietrobattista3Donatella Capalbo4Mariella Valenzise5Vito Lampasona6Annamaria Cudini7Elena Carbone8Olivia Pagliarosi9Giuseppe Maggiore10Mariacarolina Salerno11Corrado Betterle12Alessandra Fierabracci13Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Precision and Regenerative Medicine and Ionian Area, University of Bari “Aldo Moro”, Bari, ItalyResearch Unit for Innovative Therapies in Endocrinopathies, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyHepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyPediatric Endocrinology Unit, Department of Mother and Child, University Hospital Federico II, Naples, ItalyDepartment of Human Pathology of Adulthood and Childhood, Messina University, Messina, ItalySan Raffaele Hospital, IRCCS, Milan, ItalyBambino Gesù Children’s Hospital, IRCCS, Rome, ItalyBambino Gesù Children’s Hospital, IRCCS, Rome, ItalyBambino Gesù Children’s Hospital, IRCCS, Rome, ItalyHepatology, Gastroenterology and Nutrition Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyPediatric Endocrinology Unit, Department of Translational Medical Sciences, University of Naples Federico II, Naples, ItalyClinical Immunology, Padua University, Padua, ItalyBambino Gesù Children’s Hospital, IRCCS, Rome, ItalyIntroductionAutoimmune 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 methodsWe 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.ResultsBased 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.ConclusionAlthough 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172369/fullAPECEDautoimmune hepatitisautoimmune gastro-enteropathyAIREdiagnostic criteriaautoimmune gastroenteropathy |
| spellingShingle | Giorgia Paldino Maria Felicia Faienza Marco Cappa Andrea Pietrobattista Donatella Capalbo Mariella Valenzise Vito Lampasona Annamaria Cudini Elena Carbone Olivia Pagliarosi Giuseppe Maggiore Mariacarolina Salerno Corrado Betterle Alessandra Fierabracci Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies Frontiers in Immunology APECED autoimmune hepatitis autoimmune gastro-enteropathy AIRE diagnostic criteria autoimmune gastroenteropathy |
| title | Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies |
| title_full | Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies |
| title_fullStr | Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies |
| title_full_unstemmed | Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies |
| title_short | Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies |
| title_sort | analysis of a series of italian apeced patients with autoimmune hepatitis and gastro enteropathies |
| topic | APECED autoimmune hepatitis autoimmune gastro-enteropathy AIRE diagnostic criteria autoimmune gastroenteropathy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1172369/full |
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