{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:37:37Z","timestamp":1768772257184,"version":"3.49.0"},"reference-count":52,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T00:00:00Z","timestamp":1751673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Sjogren\u2019s syndrome is an autoimmune disease that may be triggered by environmental factors. While the impact of perfluoroalkyl substances (PFASs) on the human immune system has been investigated, their specific effect on Sjogren\u2019s syndrome remains unreported. We conducted this study to evaluate the association between PFAS exposure and clinical manifestations of pSS. In total, 136 patients with pSS and 148 healthy controls in the Second Affiliated Hospital of Zhejiang University School of Medicine were investigated. The concentrations of perfluoroundecanoic acid (PFUdA) in the pSS group were statistically significantly higher than those in the healthy control group. Compared to patients without leukopenia and thrombocytopenia, those with the condition had significantly lower concentrations of perfluorononanoic acid (PFNA). The serum levels of PFNA and perfluorodecanoic acid (PFDA) were found to be lower in patients with a high antinuclear antibody (ANA) titer compared to those with a low ANA titer. The serum levels of PFNA were found to be lower in patients who were anti-Sj\u00f6gren\u2019s syndrome A (anti-SSA)-positive compared to those who were anti-SSA-negative. These results indicate that the levels of serum PFASs may be correlated with the disease activity in pSS patients, and there might be an association between PFASs and the onset of pSS.<\/jats:p>","DOI":"10.3390\/toxics13070570","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T06:03:13Z","timestamp":1751868193000},"page":"570","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Perfluoroalkyl Substances on the Clinical Manifestations of Primary Sj\u00f6gren Syndrome"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8154-5931","authenticated-orcid":false,"given":"Yun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Rheumatology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hangbiao","family":"Jin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shetuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meirong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310032, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-6575","authenticated-orcid":false,"given":"Jing","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou 310009, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41584-024-01135-3","article-title":"Update on the pathophysiology and treatment of primary Sj\u00f6gren syndrome","volume":"20","author":"Baldini","year":"2024","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_2","first-page":"97","article-title":"Primary Sjogren\u2019s Syndrome","volume":"379","author":"Mariette","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/14397595.2018.1546268","article-title":"Targeting primary Sjogren\u2019s syndrome","volume":"29","author":"Odani","year":"2019","journal-title":"Mod. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/joim.13032","article-title":"Environmental factors in the pathogenesis of primary Sjogren\u2019s syndrome","volume":"287","author":"Bjork","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"7954","DOI":"10.1021\/es2011622","article-title":"Polyfluorinated compounds: Past, present, and future","volume":"45","author":"Lindstrom","year":"2011","journal-title":"Environ. Sci. Technol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1289\/ehp.10009","article-title":"Half-Life of Serum Elimination of Perfluorooctanesulfonate, Perfluorohexanesulfonate, and Perfluorooctanoate in Retired Fluorochemical Production Workers","volume":"115","author":"Olsen","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41370-018-0094-1","article-title":"A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects","volume":"29","author":"Sunderland","year":"2018","journal-title":"J. Expo. Sci. Environ. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7439","DOI":"10.1021\/es051097y","article-title":"Perfluorinated Alkyl Substances in Plasma, Liver, Brain, and Eggs of Glaucous Gulls (Larus hyperboreus) from the Norwegian Arctic","volume":"39","author":"Verreault","year":"2005","journal-title":"Environ. Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1038\/nrendo.2016.186","article-title":"Early-life exposure to EDCs: Role in childhood obesity and neurodevelopment","volume":"13","author":"Braun","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12940-018-0352-7","article-title":"Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood atopic dermatitis: A prospective birth cohort study","volume":"17","author":"Chen","year":"2018","journal-title":"Environ. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"126764","DOI":"10.1016\/j.chemosphere.2020.126764","article-title":"Perfluoroalkyl substances cause Leydig cell dysfunction as endocrine disruptors","volume":"253","author":"Zhu","year":"2020","journal-title":"Chemosphere"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114285","DOI":"10.1016\/j.envpol.2020.114285","article-title":"Associations between the serum levels of PFOS\/PFOA and IgG N-glycosylation in adult or children","volume":"265","author":"Liu","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/etc.4890","article-title":"Per- and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research","volume":"40","author":"Fenton","year":"2020","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1289\/ehp.1206449","article-title":"Ulcerative Colitis and Perfluorooctanoic Acid (PFOA) in a Highly Exposed Population of Community Residents and Workers in the Mid-Ohio Valley","volume":"121","author":"Steenland","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1136\/oemed-2014-102364","article-title":"A cohort incidence study of workers exposed to perfluorooctanoic acid (PFOA)","volume":"72","author":"Steenland","year":"2015","journal-title":"Occup. Environ. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134338","DOI":"10.1016\/j.chemosphere.2022.134338","article-title":"Per-\/polyfluoroalkyl substance concentrations in human serum and their associations with immune markers of rheumatoid arthritis","volume":"298","author":"Zhao","year":"2022","journal-title":"Chemosphere"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"119505","DOI":"10.1016\/j.envpol.2022.119505","article-title":"Evaluated serum perfluoroalkyl acids and their relationships with the incidence of rheumatoid arthritis in the general population in Hangzhou, China","volume":"307","author":"Qu","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Jin, H., Qu, J., Zhang, S., Hu, S., Xue, J., and Zhao, M. (2022). The influences of perfluoroalkyl substances on the rheumatoid arthritis clinic. BMC Immunol., 23.","DOI":"10.1186\/s12865-022-00483-7"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.chemosphere.2018.12.186","article-title":"The overlooked short- and ultrashort-chain poly- and perfluorinated substances: A review","volume":"220","author":"Ateia","year":"2019","journal-title":"Chemosphere"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"151143","DOI":"10.1016\/j.scitotenv.2021.151143","article-title":"Detection of long chain per- and polyfluoroalkyl substances (PFAS) in the benthic Golden tilefish (Lopholatilus chamaeleonticeps) and their association with microscopic hepatic changes","volume":"809","author":"Pulster","year":"2022","journal-title":"Sci. Total Environ."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Brase, R.A., Mullin, E.J., and Spink, D.C. (2021). Legacy and Emerging Per- and Polyfluoroalkyl Substances: Analytical Techniques, Environmental Fate, and Health Effects. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22030995"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/ard.61.6.554","article-title":"Classification criteria for Sj\u00f6gren\u2019s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group","volume":"61","author":"Vitali","year":"2002","journal-title":"Ann. Rheum. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7808","DOI":"10.1021\/acs.est.6b01698","article-title":"Isomer-Specific Distribution of Perfluoroalkyl Substances in Blood","volume":"50","author":"Jin","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"077018","DOI":"10.1289\/EHP275","article-title":"Serum Vaccine Antibody Concentrations in Adolescents Exposed to Perfluorinated Compounds","volume":"125","author":"Grandjean","year":"2017","journal-title":"Environ. Health Perspect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1038\/s41584-023-00932-6","article-title":"Genetics and epigenetics of primary Sjogren syndrome: Implications for future therapies","volume":"19","author":"Thorlacius","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103673","DOI":"10.1016\/j.autrev.2024.103673","article-title":"Sjogren\u2019s syndrome: Everything you always wanted to know about genetic and epigenetic factors","volume":"23","author":"Perricone","year":"2024","journal-title":"Autoimmun. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.semarthrit.2017.06.007","article-title":"Concordance of autoimmune disease in a nationwide Danish systemic lupus erythematosus twin cohort","volume":"47","author":"Svendsen","year":"2018","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","article-title":"Variation in the Human Immune System Is Largely Driven by Non-Heritable Influences","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e636","DOI":"10.1016\/S2665-9913(24)00039-0","article-title":"Precision medicine in Sj\u00f6gren\u2019s disease","volume":"6","author":"Gandolfo","year":"2024","journal-title":"Lancet Rheumatol."},{"key":"ref_30","unstructured":"ATSDR (2021). Toxicological Profile for Perfluoroalkyls."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115969","DOI":"10.1016\/j.envres.2023.115969","article-title":"Impact of PFAS exposure on prevalence of immune-mediated diseases in adults in the Czech Republic","volume":"229","author":"Rudzanova","year":"2023","journal-title":"Environ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/pr.2015.213","article-title":"Perfluoroalkyl and polyfluoroalkyl substances and indicators of immune function in children aged 12\u201319 y: National Health and Nutrition Examination Survey","volume":"79","author":"Stein","year":"2015","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1001\/jama.2011.2034","article-title":"Serum Vaccine Antibody Concentrations in Children Exposed to Perfluorinated Compounds","volume":"307","author":"Grandjean","year":"2012","journal-title":"JAMA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/all.12605","article-title":"Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children","volume":"70","author":"Smit","year":"2015","journal-title":"Allergy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.envint.2017.01.024","article-title":"Prenatal exposure to perfluoroalkyl acids and prevalence of infectious diseases up to 4years of age","volume":"104","author":"Goudarzi","year":"2017","journal-title":"Environ. Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.scitotenv.2016.03.187","article-title":"Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status","volume":"559","author":"Zhu","year":"2016","journal-title":"Sci. Total Environ."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113905","DOI":"10.1016\/j.ijheh.2021.113905","article-title":"Cross-sectional associations between serum PFASs and inflammatory biomarkers in a population exposed to AFFF-contaminated drinking water","volume":"240","author":"Barton","year":"2022","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3109\/1547691X.2015.1029147","article-title":"Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood","volume":"13","author":"Pennings","year":"2016","journal-title":"J. Immunotoxicol."},{"key":"ref_39","unstructured":"NTP (National Toxicology Program) (2019). TOX-97: Perfuorohexanoic acid (307-24-4), perfuorooctanoic acid (335-67-1), perfuorononanoic acid (375-95-1), perfuorodecanoic acid (335-76-2), WY-14643 (50892-23-4), Chemical Efects in Biological Systems (CEBS)."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1093\/toxsci\/kfn127","article-title":"Immunotoxic Effects of Perfluorononanoic Acid on BALB\/c Mice","volume":"105","author":"Fang","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.fct.2016.12.004","article-title":"Persistent alterations in immune cell populations and function from a single dose of perfluorononanoic acid (PFNA) in C57Bl\/6 mice","volume":"100","author":"Rockwell","year":"2017","journal-title":"Food Chem. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41590-020-00816-x","article-title":"The immunology of rheumatoid arthritis","volume":"22","author":"Weyand","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The pathogenesis of rheumatoid arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1093\/toxsci\/kfp019","article-title":"Alterations of Cytokines and MAPK Signaling Pathways are Related to the Immunotoxic Effect of Perfluorononanoic Acid","volume":"108","author":"Fang","year":"2009","journal-title":"Toxicol. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/1547691X.2018.1445145","article-title":"Immunotoxic and hepatotoxic effects of perfluoro-n-decanoic acid (PFDA) on female Harlan Sprague\u2013Dawley rats and B6C3F1\/N mice when administered by oral gavage for 28 days","volume":"15","author":"Frawley","year":"2018","journal-title":"J. Immunotoxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1007\/s11033-022-07272-w","article-title":"The toxicity of perfluorodecanoic acid is mainly manifested as a deflected immune function","volume":"49","author":"Li","year":"2022","journal-title":"Mol. Biol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1515\/reveh-2023-0146","article-title":"Association between exposure to per- and polyfluoroalkyl substances and levels of lipid profile based on human studies","volume":"40","author":"Song","year":"2024","journal-title":"Rev. Environ. Health"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"139491","DOI":"10.1016\/j.chemosphere.2023.139491","article-title":"Perfluoroundecanoic acid induces DNA damage, reproductive and pathophysiological dysfunctions via oxidative stress in male Swiss mice","volume":"338","author":"Ogunsuyi","year":"2023","journal-title":"Chemosphere"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"114578","DOI":"10.1016\/j.fct.2024.114578","article-title":"Systemic and immunotoxicity induced by topical application of perfluorohexane sulfonic acid (PFHxS) in a murine model","volume":"186","author":"Weatherly","year":"2024","journal-title":"Food Chem. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"108421","DOI":"10.1016\/j.reprotox.2023.108421","article-title":"Reproductive and immune effects emerge at similar thresholds of PFHxS in deer mice","volume":"120","author":"Narizzano","year":"2023","journal-title":"Reprod. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.envint.2015.12.020","article-title":"Perfluoroalkyl substances and food allergies in adolescents","volume":"88","author":"Buser","year":"2016","journal-title":"Environ. Int."},{"key":"ref_52","first-page":"e06223","article-title":"Risk to human health related to the presence of perfluoroalkyl substances in food","volume":"18","author":"Schrenk","year":"2020","journal-title":"EFSA J."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/7\/570\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:05:06Z","timestamp":1760033106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/7\/570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,5]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["toxics13070570"],"URL":"https:\/\/doi.org\/10.3390\/toxics13070570","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,5]]}}}