{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:42:40Z","timestamp":1770831760912,"version":"3.50.1"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["GM104938"],"award-info":[{"award-number":["GM104938"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AR47431"],"award-info":[{"award-number":["AR47431"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["DE017561"],"award-info":[{"award-number":["DE017561"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Sj\u00f6gren\u2019s Disease (SjD) subjects have decreased lacrimal\/salivary gland function. Studies have proposed that autoantibodies targeting G-protein-coupled muscarinic acetylcholine-type-3-receptor (M3R) are potential clinical markers for SjD. We hypothesized that rabbits\/mice immunized with 4-hydroxy-2-nonenal (HNE)-modified\/unmodified Ro60 will develop an autoimmunity, specifically a SjD phenotype, thus expressing increased levels of anti-M3R antibodies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We immunized two rabbits each with 10 mM HNE-modified Ro60\/unmodified Ro60 antigen or Ro274-290\/Ro413-428\/Ro500-517 Ro60 peptides. Two rabbits each were immunized with either M3R second extracellular loop (ECL2) or M3R ECL3 peptide. Finally, five groups of BALB\/c mice were immunized as follows\u2014Group-I immunized with Ro60, Groups-II\u2014IV immunized with Ro60 modified with 0.4 mM (low), 2 mM (medium), and 10 mM (high) HNE, respectively and Group-V\u2014Freund\u2019s adjuvant. Serum antibodies to M3R ECL2\/ECL3\/Ro60\/La or Sm were detected by ELISA. Functional assays were also performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Immunization with HNE-modified Ro60\/unmodified Ro60 antigen or Ro274\/Ro 413\/Ro500 peptides induced a rapid intermolecular epitope spreading to M3R ECL2\/ECL3, especially to M3R ECL3 in HNE-Ro immunized rabbits. These animals did not bind to scrambled M3R peptides. Ro60-immunized rabbit IgG inhibited M3R activity in a functional assay. Rabbits immunized with ECL2\/ECL3 developed high reactivity to Ro60 but not against Sm\/RNP. We found a differential antibody-induction against M3R ECL2 with Group-3 mice developing significant reactivity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data show induction of increasing anti-M3R antibodies in rabbits immunized with Ro60\/HNE-Ro60 or Ro60 peptides and differential induction of these antibodies in mice immunized with Ro60 modified with increasing HNE. These findings suggest that M3R ECL2\/ECL3 are involved in SjD autoimmunity progression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cei\/uxae114","type":"journal-article","created":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T01:31:46Z","timestamp":1733880706000},"source":"Crossref","is-referenced-by-count":1,"title":["Experimental induction of anti-muscarinic type-3-receptor extracellular loop antibodies by immunization with 4-hydroxy-2-nonenal modified Ro60 and unmodified Ro60"],"prefix":"10.1093","volume":"219","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7877-6859","authenticated-orcid":false,"given":"Biji T","family":"Kurien","sequence":"first","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devavrat","family":"Dave","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Tsaliki","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed M S","family":"Quadri","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Departments of Medicine and Pathology, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie M","family":"Lewis","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Hal","family":"Scofield","sequence":"additional","affiliation":[{"name":"Arthritis & Clinical Immunology Program, Oklahoma Medical Research Foundation , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Department of Veterans Affairs Medical Center , Oklahoma City, Oklahoma, OK ,","place":["USA"]},{"name":"Departments of Medicine and Pathology, University of Oklahoma 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