Circulating anti-hypothalamus antibodies in celiac patients: tissue transglutaminase friend or foe?
Active CD; Free-gluten CD; Anti-hypothalamus autoantibodies; Anti-tTG autoantibodies; Mucosal damage; Ghrelin
Journal
Immunologic research
ISSN: 1559-0755
Titre abrégé: Immunol Res
Pays: United States
ID NLM: 8611087
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
03
08
2022
accepted:
09
05
2023
medline:
27
11
2023
pubmed:
24
5
2023
entrez:
23
5
2023
Statut:
ppublish
Résumé
Celiac disease (CD) is an autoimmune disease with inflammatory characteristics, having a condition of chronic malabsorption, affecting approximately 1% of the population at any age. In recent years, a concrete correlation between eating disorders and CD has emerged. Hypothalamus plays a central role in determining eating behaviour, regulating appetite and, consequently, food intake. One hundred and ten sera from celiac patients (40 active and 70 following a gluten-free diet) were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. In addition, ghrelin was measured by ELISA. As control, 45 blood serums from healthy age matched were analysed. Among active CD, all patients resulted positive for anti-hypothalamus autoantibodies and sera showed significantly higher levels of ghrelin. All of the free-gluten CD were negative for anti-hypothalamus autoantibodies and had low levels of ghrelin, as well as healthy controls. Of interest, anti-hypothalamic autoantibodies directly correlate with anti-tTG amounts and with mucosal damage. In addition, competition assays with recombinant tTG showed a drastically reduction of anti-hypothalamic serum reactivity. Finally, ghrelin levels are increased in CD patients and correlated with anti-tTG autoantibodies and anti-hypothalamus autoantibodies. This study demonstrates for the first time the presence of anti-hypothalamus antibodies and their correlation with the severity of the CD. It also allows us to hypothesize the role of tTG as a putative autoantigen expressed by hypothalamic neurons.
Identifiants
pubmed: 37221348
doi: 10.1007/s12026-023-09394-0
pii: 10.1007/s12026-023-09394-0
pmc: PMC10667380
doi:
Substances chimiques
Ghrelin
0
Protein Glutamine gamma Glutamyltransferase 2
EC 2.3.2.13
Transglutaminases
EC 2.3.2.13
Autoantibodies
0
Immunoglobulin A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
839-848Subventions
Organisme : Università degli Studi di Genova (IT)
ID : Project FRA-2019.
Informations de copyright
© 2023. The Author(s).
Références
Lancet. 2018 Jan 6;391(10115):70-81
pubmed: 28760445
Gastroenterol Res Pract. 2013;2013:491657
pubmed: 24369457
Diabetes Care. 1992 Oct;15(10):1402-12
pubmed: 1425109
Adv Genomics Genet. 2015;5:131-150
pubmed: 27013903
Nutrients. 2019 Jan 03;11(1):
pubmed: 30609862
Front Pediatr. 2018 Nov 21;6:350
pubmed: 30519552
J Pediatr Gastroenterol Nutr. 2018 Jan;66(1):53-57
pubmed: 28562523
Gut. 2013 Jan;62(1):43-52
pubmed: 22345659
Pediatrics. 2017 May;139(5):
pubmed: 28557761
J Clin Endocrinol Metab. 1987 Nov;65(5):885-90
pubmed: 2444616
Arch Dis Child. 1990 Aug;65(8):909-11
pubmed: 2205160
Br J Psychiatry. 2012 May;200(5):374-80
pubmed: 22442099
Nat Genet. 2009 Jun;41(6):703-7
pubmed: 19430480
Nat Rev Immunol. 2016 May 27;16(6):341-52
pubmed: 27231050
Mol Cell Endocrinol. 2011 Jun 20;340(1):44-58
pubmed: 21565248
Expert Rev Gastroenterol Hepatol. 2016;10(5):565-9
pubmed: 27003627
Curr Opin Psychiatry. 2016 Nov;29(6):340-5
pubmed: 27662598
Am J Gastroenterol. 2003 Nov;98(11):2474-8
pubmed: 14638351
Gut Liver. 2016 Jul 15;10(4):587-94
pubmed: 27074817
J Clin Invest. 2004 Jul;114(1):57-66
pubmed: 15232612
Autoimmunity. 2020 Jun;53(4):225-230
pubmed: 32157915
Curr Opin Pediatr. 2013 Aug;25(4):463-70
pubmed: 23838835
Nutrition. 2008 Sep;24(9):854-9
pubmed: 18725083
Nat Rev Rheumatol. 2017 Feb;13(2):100-109
pubmed: 28053336
J Clin Gastroenterol. 2006 Mar;40(3):191-4
pubmed: 16633118
Scand J Gastroenterol. 2005 Apr;40(4):430-6
pubmed: 16028437
Am J Psychiatry. 2017 Sep 1;174(9):850-858
pubmed: 28494655
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17155-60
pubmed: 12486250
Cell Mol Immunol. 2019 Jun;16(6):625-626
pubmed: 30979971
J Pediatr. 2004 Jan;144(1):30-5
pubmed: 14722515
Intern Med J. 2009 Nov;39(11):784
pubmed: 19220553
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14865-70
pubmed: 16195379
Eat Weight Disord. 2022 Oct;27(7):2481-2496
pubmed: 35297008
Neuropsychiatr Dis Treat. 2017 May 04;13:1211-1214
pubmed: 28496327
United European Gastroenterol J. 2015 Apr;3(2):136-45
pubmed: 25922673
Brain Res Bull. 2001 Oct-Nov 1;56(3-4):173-82
pubmed: 11719248
Aliment Pharmacol Ther. 2006 Apr 1;23(7):907-13
pubmed: 16573793
J Neurosci Res. 2018 Jul;96(7):1150-1158
pubmed: 29570839
Clin Endocrinol (Oxf). 2003 Nov;59(5):649-54
pubmed: 14616891
Nat Immunol. 2021 Mar;22(3):312-321
pubmed: 33510463
BMJ. 2000 Jun 10;320(7249):1563-6
pubmed: 10845962