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Rheumatic autoimmune diseases (RAD) are known to be associated with chronic inflammation and an ERS state. However, the activation of UPR signaling pathways is not completely understood in Sj\u00f6gren\u2019s disease (SD). This study evaluated the expression of ERS-related genes in glandular tissue of patients with primary SD (pSD), associated SD (aSD) with other autoimmune diseases, and non-Sj\u00f6gren sicca syndrome (NSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a cross-sectional study, minor salivary gland biopsies were obtained from 44 patients with suspected SD and 13 healthy controls (HC). Patients were classified as pSD, aSD, or NSS based on clinical, serological, and histological assessment. Histopathological analysis and mRNA expression analysis of genes associated with ERS and UPR (PERK, XBP1, ATF-6, ATF-4, CANX, CALR, CHOP, and BIP) were performed on the samples. Differences between groups (pSD, aSD, NSS, and HC) were assessed. The influence of chloroquine (CQ) on the ER was also investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-eight SD patients showed increased expression of PERK (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0117) and XBP1 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0346), and reduced expression of ATF-6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003) and CHOP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003), compared to the HC group. Increased expression of BIP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), PERK (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003), CALR (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), and CANX (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0111) was also observed in the SD group compared to the NSS group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916). Patients receiving CQ (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200916) showed a significant increase in ATF-6 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0317) compared to patients not taking the medication (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Altogether, the results suggest a greater activation of the ERS and UPR genes in patients with SD, especially in the pSD group. Antimalarial drugs, like CQ, used to treat RAD, may affect the ER function in exocrine glands.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s42358-024-00430-7","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T03:39:08Z","timestamp":1736307548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Endoplasmic reticulum stress in the salivary glands of patients with primary and associated Sj\u00f6gren\u2019s disease, and non-Sj\u00f6gren\u2019s sicca syndrome: a comparative analysis and the influence of chloroquine"],"prefix":"10.1186","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7349-5273","authenticated-orcid":false,"given":"Graziela Vieira","family":"Cavalcanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9196-7422","authenticated-orcid":false,"given":"Fabiola Reis","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4496-4883","authenticated-orcid":false,"given":"Rafael Ferraz","family":"Bannitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3744-8947","authenticated-orcid":false,"given":"Natalia Aparecida","family":"de Paula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-9239","authenticated-orcid":false,"given":"Ana Carolina Fragoso","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-7313","authenticated-orcid":false,"given":"Eduardo Melani","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Chiorini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3019-8949","authenticated-orcid":false,"given":"Hilton Marcos Alves","family":"Ricz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9123-2728","authenticated-orcid":false,"given":"Denny Marcos","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1350-1125","authenticated-orcid":false,"given":"Maria Cristina","family":"Foss-Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2153-6512","authenticated-orcid":false,"given":"Luiz Carlos Conti","family":"de Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"issue":"1","key":"430_CR1","doi-asserted-by":"publisher","first-page":"16047","DOI":"10.1038\/nrdp.2016.47","volume":"2","author":"P Brito-Zer\u00f3n","year":"2016","unstructured":"Brito-Zer\u00f3n P, Baldini C, Bootsma H, et al. 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The study protocol was approved by the Ethics Committee of the Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Brazil (protocol number CAAE: 09299318.2.0000.5440). Informed consent was obtained from all individual participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2"}}