Tryptophan hydroxylase autoantibodies as markers of a distinct autoimmune gastrointestinal component of autoimmune polyendocrine syndrome type 1

Autor: Lucia Ghizzoni, Mario Plebani, Fabio Farinati, G. Tonini, Riccardo Scarpa, Mariacarolina Salerno, B. Rees Smith, Giorgio Radetti, Stefano Masiero, F. De Luca, Jadwiga Furmaniak, Lorenzo Norberto, Roberta Giordano, Corrado Betterle, Shu Chen, Rita Alaggio, Luca Morlin
Přispěvatelé: R., Scarpa, R., Alaggio, L., Norberto, J., Furmaniak, S., Chen, B., Rees Smith, S., Masiero, L., Morlin, M., Plebani, F., De Luca, Salerno, Mariacarolina, R., Giordano, G., Radetti, L., Ghizzoni, G., Tonini, F., Farinati, C., Betterle
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Male
IRRITABLE-BOWEL-SYNDROME
CANDIDIASIS-ECTODERMAL-DYSTROPHY
SYNDROME TYPE-I
PLASMA 5-HYDROXYTRYPTAMINE
CONSTIPATION-PREDOMINANT
ENTEROCHROMAFFIN CELLS
SEROTONIN TRANSPORTER
ULCERATIVE-COLITIS
ENDOCRINE-CELLS
DISEASE
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Tryptophan Hydroxylase
medicine.disease_cause
Biochemistry
Autoimmunity
0302 clinical medicine
Endocrinology
Child
Polyendocrinopathies
Autoimmune
0303 health sciences
Gastrointestinal tract
medicine.diagnostic_test
Tryptophan
Autoimmune Polyendocrine Syndrome Type 1
IRRITABLE-BOWEL-SYNDROME
CANDIDIASIS-ECTODERMAL-DYSTROPHY
SYNDROME TYPE-I
PLASMA 5-HYDROXYTRYPTAMINE
CONSTIPATION-PREDOMINANT
ENTEROCHROMAFFIN CELLS
SEROTONIN TRANSPORTER
ULCERATIVE-COLITIS
ENDOCRINE-CELLS
DISEASE
Middle Aged
3. Good health
Enterochromaffin cell
030211 gastroenterology & hepatology
Female
Adult
medicine.medical_specialty
Serotonin
Adolescent
Biology
03 medical and health sciences
Antigens
CD
Internal medicine
Biopsy
medicine
Humans
030304 developmental biology
Aged
Autoantibodies
Biochemistry (medical)
Autoantibody
Tryptophan hydroxylase
medicine.disease
Gastrointestinal Tract
Autoimmune polyendocrine syndrome type 1
Zdroj: Università degli Studi di Padova-IRIS
The Journal of Clinical Endocrinology & Metabolism; Vol 98
Popis: Background:Autoantibodies to tryptophan hydroxylase (TPHAbs) directed against serotonin-producing enterochromaffin cells (EC) have been reported in autoimmune-polyendocrine-syndrome type 1 (APS-1) patients with gastrointestinal dysfunction (GID). Serotonin plays a critical role in enteric function and its peripheral blood levels reflect serotonin release from the gastrointestinal tract.Aims:We test the hypothesis that TPHAbs mark a distinct autoimmune component of APS-1 characterized by an autoimmune attack toward EC, which results in clinical GID.Methods:TPHAbs were measured in 64 APS-1 patients. Endoscopy with gastric (antrum/body) and duodenal biopsy was carried in 16 TPHAbs+ patients (8 with and 8 without GID) and in 2 TPHAbs- patients (without GID). Immunohistochemistry of biopsy specimens was carried out using antibodies to serotonin, chromogranin-A, CD3, CD4, CD8, and CD20. Serotonin serum levels were measured in TPHAbs+ and TPHAbs- patients who had endoscopy.Results:Thirty-seven of 64 patients were TPHAbs+ (11/12 with GID and 26/52 without GID; P < .001). Gastric and duodenal biopsies in all 8 TPHAb+ patients with GID showed lymphocytic infiltration with increased CD3+CD8+ intraepithelial lymphocytes and absence of EC. Furthermore, mean serotonin serum levels were below the normal range in TPHAb+ patients with GID (P < .01). In 8 TPHAb+ patients without GID gastric and duodenal biopsies showed different grades of inflammatory infiltration and reduced number of EC. Mean serotonin serum levels were near the lower limit of the normal range. In all TPHAbs+ patients the biopsies showed a reduced number of chromogranin-A positive cells consistent with enteroendocrine cells depletion. TPHAbs- patients without GID showed normal gastrointestinal mucosa and serotonin serum levels.Conclusions:TPHAbs appear to be markers of a distinct autoimmune component of APS-1. Progressive involvement of the gastrointestinal EC leads to the transition from preclinical to clinical disease, characterized by GID and reduced serotonin serum levels.
Databáze: OpenAIRE
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