Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia
| Autor: | Ángel Priego‐Ranero, Ghislain Opdenakker, Norma Uribe‐Uribe, Diana Aguilar‐León, Carlos A. Nuñez‐Álvarez, Diego F. Hernández‐Ramírez, Elizabeth Olivares‐Martínez, Enrique Coss‐Adame, Miguel A. Valdovinos, Janette Furuzawa‐Carballeda, Gonzalo Torres‐Villalobos |
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| Rok vydání: | 2022 |
| Předmět: |
History
Polymers and Plastics active MMP-9 Manometry Physiology AUTOIMMUNITY PATHOGENESIS Clinical Neurology anti-myenteric autoantibodies Autoantigens Industrial and Manufacturing Engineering Esophageal Sphincter Lower Humans Esophageal Motility Disorders Business and International Management Autoantibodies Science & Technology Gastroenterology & Hepatology Endocrine and Autonomic Systems Neurosciences Gastroenterology PNMA Fibrosis MODEL Esophageal Achalasia achalasia Cross-Sectional Studies Matrix Metalloproteinase 9 GAD65 ANTIBODIES Ta2 AUTOANTIBODIES Neurosciences & Neurology Esophagogastric Junction Life Sciences & Biomedicine |
| Zdroj: | Neurogastroenterology & Motility. 34 |
| ISSN: | 1365-2982 1350-1925 |
| DOI: | 10.1111/nmo.14348 |
| Popis: | BACKGROUND: Serum anti-myenteric autoantibodies define autoimmune achalasia and tissue MMP-9 activity may locally process autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients. METHODS: Biopsies of the LES muscle from 36 achalasia patients, 6 esophagogastric junction outflow obstruction (EGJOO) patients, and 16 transplant donors (TD) were compared in a blind cross-sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S-100, P substance, and MMP-9 proteoforms in tissue were assessed by H&E and Picrosirius Red staining and immunohistochemistry analysis. Anti-neuronal antibodies, onconeural antigens, recoverin, SOX-1, titin, zic4, GAD65, and Tr were evaluated by immunoblot/line assay. KEY RESULTS: Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP-9, as compared with EGJOO and TD. Moreover, lower ganglion cell percentages and cell of Cajal percentages were determined in esophageal tissues of achalasia patients versus TD. The tissues of achalasia versus EGJOO patients had higher GAD65 and PNMA2 protein expression. Unexpectedly, these proteins were absent in TD tissue. S-100 and P substance had similar expression levels in tissues of achalasia patients versus TD and EGJOO. Most of the achalasia sera had anti-GAD65 (83%) and anti-PNMA2 (90%) autoantibodies versus EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively). CONCLUSIONS AND INFERENCES: Tissue-specific ectopic expression of GAD65 and PNMA/Ta2 and active MMP-9, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and/or perpetuating autoimmune disease. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:34 issue:9 ispartof: location:England status: published |
| Databáze: | OpenAIRE |
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