{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:29:48Z","timestamp":1787596188113,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum anti\u2010myenteric autoantibodies define autoimmune achalasia and tissue MMP\u20109 activity may locally process autoantigenic proteins in the muscle of the lower esophageal sphincter (LES) of achalasia patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2010sectional study. Histological characteristics such as inflammation, fibrosis, presence of ganglion cells, cells of Cajal, GAD65, PNMA2, S\u2010100, P substance, and MMP\u20109 proteoforms in tissue were assessed by H&amp;E and Picrosirius Red staining and immunohistochemistry analysis. Anti\u2010neuronal antibodies, onconeural antigens, recoverin, SOX\u20101, titin, zic4, GAD65, and Tr were evaluated by immunoblot\/line assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Tissue of achalasia patients had heterogeneous inflammatory infiltrates with fibrosis and contrasting higher levels of activated MMP\u20109, 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\u2010100 and P substance had similar expression levels in tissues of achalasia patients versus TD and EGJOO. Most of the achalasia sera had anti\u2010GAD65 (83%) and anti\u2010PNMA2 (90%) autoantibodies versus EGJOO (17% and 33%, respectively) and healthy volunteers (10% and 0%, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Inferences<\/jats:title>\n                    <jats:p>Tissue\u2010specific ectopic expression of GAD65 and PNMA\/Ta2 and active MMP\u20109, associated with the presence of specific autoantibodies directed against these proteins, might participate in the pathophysiology of achalasia triggering and\/or perpetuating autoimmune disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.14348","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T08:50:51Z","timestamp":1646643051000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Autoantigen characterization in the lower esophageal sphincter muscle of patients with achalasia"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-6438","authenticated-orcid":false,"given":"\u00c1ngel","family":"Priego\u2010Ranero","sequence":"first","affiliation":[{"name":"Department of Immunology and Rheumatology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Tlalpan Mexico CDMX Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1714-2294","authenticated-orcid":false,"given":"Ghislain","family":"Opdenakker","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Transplantation Laboratory of Immunobiology Rega Institute for Medical Research and University Hospitals UZ Leuven KU Leuven University of Leuven  Leuven 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Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8569-2792","authenticated-orcid":false,"given":"Enrique","family":"Coss\u2010Adame","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Tlalpan Mexico CDMX Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-1433","authenticated-orcid":false,"given":"Miguel A.","family":"Valdovinos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5804-7221","authenticated-orcid":false,"given":"Janette","family":"Furuzawa\u2010Carballeda","sequence":"additional","affiliation":[{"name":"Department of Immunology and Rheumatology Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n  Tlalpan Mexico CDMX Mexico"},{"name":"Escuela 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