Anania, Caterina

Cucchiara, Salvatore

Lenzi, Andrea

Montuori, Monica

Morano, Susanna

Panimolle, Francesca

Tiberti, Claudio

Trovato, CHIARA MARIA

Valitutti, Francesco

Vestri, Anna Rita

Diabetes Care

English

TIBERTI, Claudio

PANIMOLLE, FRANCESCA

TROVATO, CHIARA MARIA

ANANIA, Caterina

VALITUTTI, FRANCESCO

VESTRI, Anna Rita

LENZI, Andrea

CUCCHIARA, Salvatore

MORANO, Susanna

Archivio della ricerca- Università di Roma La Sapienza

Screening for Type 1 Diabetes–, Thyroid-,Gastric-, and Adrenal-Specific HumoralAutoimmunity in 529 Childrenand Adolescents With Celiac Diseaseat Diagnosis Identifies as PositiveOne in Every Nine PatientsDiabetes Care 2017;40:e10–e11 | DOI: 10.2337/dc16-2095Organ-specific autoimmune disorders areoften associated with celiac disease (CD)(1,2). Most studies investigated the fre-quency of CD humoral autoimmunity inpatients at diagnosis of an organ-specificautoimmune disorder or along its course.Conversely, only two studies, dating backto the early 2000s, were aimed at deter-mining the frequency and co-occurrenceof organ-specific autoimmunity in CDpatients at diagnosis (3,4). These studiesreported discordant, excessively highpositivities for diabetes-specific autoim-munity (12.2% and 31.6%, respectively)that may be explained by the small num-ber of patients investigated and the useof, at least in part, outdated techniquessuch as islet cell autoantibody assay.On thesebases, our aimwas toevaluatein a large cohort of CD patients at diagno-sis the real frequency and co-occurrenceof humoral immunoreactivity specific offour organ-specific autoimmune disordersknown to be associated to CD, namely,type 1 diabetes (T1D), autoimmune thy-roid disease (HT), autoimmune atrophicgastritis (AG), and Addison disease (AD).In particular, the immune response di-rected against insulin (INS), GAD, tyrosinephosphatase 2(aa 605-979) (IA-2), zinc cationefflux transporter (ZnT8), thyroid peroxi-dase, enzyme steroid 21-hydroxylase,and parietal cells was investigated in 529biopsy-confirmed CD patients at diseasediagnosis (332 girls/197 boys, age range3.0–17.7 years) and compared withthat found in 264 anti-transglutaminaseautoantibody–negative healthy controlsubjects (104 girls/160 boys; age range3.0–18.0 years).Of 529 CD patients, 11.7% were posi-tive for at least one of the organ-specificFigure 1—The upper part of the figure shows the frequencies of CD patients and healthy controlsubjects positive for at least one of the organ-specific autoantibodies (Abs) investigated in thestudy. The lower part of the figure shows the frequency distribution of the organ-specificautoantibody-positive CD patients and healthy control subjects according to each single disease.21(OH), steroid 21-hydroxylase; APC, parietal cell; TPO, thyroid peroxidase.1Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy2Department of Pediatrics, Pediatric Gastroenterology and Liver Unit, “Sapienza” University of Rome, Rome, Italy3Department of Public Health and Infectious Diseases, “Sapienza” University of Rome, Rome, ItalyCorresponding author: Susanna Morano, susanna.morano@uniroma1.it.Received 20 September 2016 and accepted 28 October 2016.© 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit,and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.Claudio Tiberti,1 Monica Montuori,2Francesca Panimolle,1Chiara M. Trovato,2 Caterina Anania,2Francesco Valitutti,2 Anna R. Vestri,3Andrea Lenzi,1 Salvatore Cucchiara,2and Susanna Morano1e10 Diabetes Care Volume 40, February 2017e-LETTERS–OBSERVATIONSantibodies investigated (Fig. 1) morefrequently than control subjects (6.4%,P 5 0.023), with T1D-specific immuneresponse significantly higher comparedwith HT and adrenal (2.1%, P 5 0.006and 0.6%, P , 0.0001, respectively) butnot gastric immunoreactivities (4.2%).Only 4.8% of autoantibody-positiveCD patients showed more than onedisease-specific immunoreactivity. AmongCD T1D-specific immunoreactivities,GAD autoantibodies were significantlymore frequent (62.1%) relative to INS,IA-2, and ZnT8 autoantibodies (31.0%,P 5 0.034; 20.7%, P 5 0.003; and13.8%, P 5 0.0003, respectively). Morethan 20% of CD patients with T1D au-toimmunity were positive for two tothree related autoantibodies. A highpercentage of CD patients (91.9%),which includes among others all of theT1D, AG, and AD autoantibody-positivepatients, did not present with theclinical signs of the related disease.Organ-specific autoantibody-positiveCD patients increased with age at diag-nosis (P for trend 5 0.018). The overallfrequency of organ-specific autoim-munity in CDboys/girls and symptomatic/asymptomatic patients was not signifi-cantly different.The finding that about one of everynine CD patients was positive for at leastone T1D-, HT-, AG-, or adrenal-specific hu-moral autoantibody demonstrates the im-portance to evaluate the organ-specificautoimmunity at CD diagnosis. Our resultsrevalue downward the prevalences re-ported so far in literature, which dateback to the early 2000s. Most of theorgan-specific autoantibody-positive CDpatients identified in this study were notdiagnosed for, but are just at risk todevelop, an organ-specific disease. Inthis light, it will be extremely importantfor future evaluation of the gluten-withdrawal effects on the developmentof organ-specific diseases after CD diagno-sis. Finally, our data provide thefirst exper-imental confirmation of the hypothesis (5)that age at diagnosis is the only significantpredictor variable of developing an addi-tional autoimmune disease in CD patients.Acknowledgments. The authors thank FlaviaAmaro and Lucilla Pezza (Department of Pedi-atrics, PediatricGastroenterology and LiverUnit,“Sapienza” University of Rome) for their contri-butions to the data collection.Funding. This work was supported by the Ital-ian ResearchMinistry (PRIN no. 2010JS3PMZ_011)(to S.M.).Duality of Interest. No potential conflicts ofinterest relevant to this article were reported.Author Contributions. C.T. contributed to datacollection, statistical analysis, and data interpreta-tion and wrote and revised the manuscript. M.M.and S.M. contributed to data collection and in-terpretation and revised the manuscript. F.P. andC.M.T. contributed to data collection and revisedthemanuscript. C.A., F.V.,A.L., andS.C. contributedto data interpretation and revised the manuscript.A.R.V. contributed to statistical analysis and re-vised the manuscript. S.M. is the guarantor of thiswork and, as such, had full access to all the data inthe study and takes responsibility for the integrityof the data and the accuracy of the data analysis.References1. Kelly CP, Bai JC, Liu E, Leffler DA. Celiac dis-ease: clinical spectrum and management. Gas-troenterology 2015;148:1175–11862. Lauret E, Rodrigo L. Celiac disease andautoimmune-associated conditions. BiomedRes Int 2013;2013:127593. Ventura A, Neri E, Ughi C, Leopaldi A, Citta` A,Not T. Gluten-dependent diabetes-related andthyroid-related autoantibodies in patients withceliac disease. J Pediatr 2000;137:263–2654. Toscano V, Conti FG, Anastasi E, et al. Impor-tance of gluten in the induction of endocrineautoantibodies and organ dysfunction in ado-lescent celiac patients. Am J Gastroenterol2000;95:1742–17485. Ventura A, Magazzu` G, Greco L. Duration ofexposure to gluten and risk for autoimmune dis-orders in patients with celiac disease. SIGEP StudyGroup for Autoimmune Disorders in Celiac Dis-ease. Gastroenterology 1999;117:297–303care.diabetesjournals.org Tiberti and Associates e11

Screening for type 1 diabetes-, thyroid-, gastric-, and adrenal-specific humoral autoimmunity in 529 children and adolescents with celiac disease at diagnosis identifies as positive one in every nine patients

Claudio Tiberti

Monica Montuori

Francesca Panimolle

Chiara M. Trovato

Caterina Anania

Francesco Valitutti

Anna R. Vestri

Andrea Lenzi

Salvatore Cucchiara

Susanna Morano

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Screening for Type 1 Diabetes–, Thyroid-, Gastric-, and Adrenal-Specific Humoral Autoimmunity in 529 Children and Adolescents With Celiac Disease at Diagnosis Identifies as Positive One in Every Nine Patients

https://iris.uniroma1.it/bitstream/11573/952460/1/Tiberti_Screening-Type1-Diabetes_2017.pdf

Screening for type 1 diabetes-, thyroid-, gastric-, and adrenal-specific humoral autoimmunity in 529 children and adolescents with celiac disease at diagnosis identifies as positive one in every nine patients

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