{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:43:48Z","timestamp":1780440228365,"version":"3.54.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T00:00:00Z","timestamp":1677110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"NIDCR","doi-asserted-by":"crossref","award":["1ZIADE000695"],"award-info":[{"award-number":["1ZIADE000695"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2014\/23211-0"],"award-info":[{"award-number":["2014\/23211-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"crossref","award":["302355\/2017-0"],"award-info":[{"award-number":["302355\/2017-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2014\/23211-0"],"award-info":[{"award-number":["2014\/23211-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"crossref","award":["2014\/23211-0"],"award-info":[{"award-number":["2014\/23211-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Takeda Science Foundation Research Fellowship"},{"name":"JSPS Research Fellowship for Japanese Biomedical and Behavioral Researchers at the NIH"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Hydroxychloroquine (HCQ) is a lysosomotropic agent that is commonly used for treating Sj\u00f6gren\u2019s disease (SjD). However, its efficacy is controversial because of the divergent response to the drug among patients. In a subgroup of SjD patients, lysosome-associated membrane protein 3 (LAMP3) is elevated in expression in the salivary glands and promotes lysosomal dysregulation and lysosome-dependent apoptotic cell death. In this study, chloroquine (CQ) and its derivative HCQ were tested for their ability to prevent LAMP3-induced apoptosis, <jats:italic>in vitro<\/jats:italic> and on a mouse model of SjD. In addition, efficacy of HCQ treatment was retrospectively compared between high <jats:italic>LAMP3<\/jats:italic> mRNA expression in minor salivary glands and those with <jats:italic>LAMP3<\/jats:italic> mRNA levels comparable with healthy controls. Study results show that CQ treatment stabilized the lysosomal membrane in LAMP3-overexpressing cells via deactivation of cathepsin B, resulting in decreased apoptotic cell death. In mice with established SjD-like phenotype, HCQ treatment also significantly decreased apoptotic cell death and ameliorated salivary gland hypofunction. Retrospective analysis of SjD patients found that HCQ tended to be more effective in improving disease activity index, symptom severity and hypergammaglobulinemia in patients with high <jats:italic>LAMP3<\/jats:italic> expression compared those with normal <jats:italic>LAMP3<\/jats:italic> expression. Taken together, these findings suggested that by determining salivary gland <jats:italic>LAMP3<\/jats:italic> mRNA level, a patient\u2019s response to HCQ treatment could be predicted. This finding may provide a novel strategy for guiding the development of more personalized medicine for SjD.<\/jats:p>","DOI":"10.1371\/journal.pone.0282227","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T18:35:11Z","timestamp":1677177311000},"page":"e0282227","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Salivary gland LAMP3 mRNA expression is a possible predictive marker in the response to hydroxychloroquine in Sj\u00f6gren\u2019s 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