{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:44:12Z","timestamp":1792633452477,"version":"4.5.0"},"reference-count":133,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T00:00:00Z","timestamp":1515628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell communication, proliferation, differentiation and survival. Zinc plays also a role in regulating the immune system with implications in pathologies where zinc deficiency and inflammation are observed. In order to examine the experimental evidence reported in the literature regarding zinc levels in the body of patients with autoimmune disorders compared to control individuals, a systematic review and meta-analysis were performed. From 26,095 articles identified by literature search, only 179 of them were considered potentially relevant for our study and then examined. Of the 179 articles, only 62 satisfied the inclusion criteria. Particularly for Fixed Model, Zn concentration in both serum (mean effect = \u22121.19; confidence interval: \u22121.26 to \u22121.11) and plasma (mean effect = \u22123.97; confidence interval: \u22124.08 to \u22123.87) samples of autoimmune disease patients was significantly lower than in controls. The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.<\/jats:p>","DOI":"10.3390\/nu10010068","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T13:36:15Z","timestamp":1515677775000},"page":"68","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-4254","authenticated-orcid":false,"given":"Alessandro","family":"Sanna","sequence":"first","affiliation":[{"name":"Department of Civil, Environmental Engineering and Architecture, University of Cagliari, 09123 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5768-391X","authenticated-orcid":false,"given":"Davide","family":"Firinu","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences and Public Health, Monserrato Campus, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0481-092X","authenticated-orcid":false,"given":"Patrizia","family":"Zavattari","sequence":"additional","affiliation":[{"name":"Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, 09042 Monserrato, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6812-5921","authenticated-orcid":false,"given":"Paolo","family":"Valera","sequence":"additional","affiliation":[{"name":"Department of Civil, Environmental Engineering and Architecture, University of Cagliari, 09123 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,11]]},"reference":[{"key":"ref_1","first-page":"293","article-title":"Etude chimique sur la vegetation","volume":"11","author":"Raulin","year":"1869","journal-title":"Ann. Sci. Nat. Bot. Biol. Veg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wessels, I., Maywald, M., and Rink, L. (2017). Zinc as a Gatekeeper of Immune Function. Nutrients, 9.","DOI":"10.3390\/nu9121286"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1023\/A:1012905406548","article-title":"Functions of zinc in signaling, proliferation and differentiation of mammalian cells","volume":"14","author":"Beyersmann","year":"2001","journal-title":"Biometals"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1301\/00296640260085877","article-title":"Cellular transporter for zinc","volume":"60","author":"Harris","year":"2002","journal-title":"Nutr. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/nu4070676","article-title":"Zinc and Regulation of inflammatory cytokines: Implications for cardiometabolic disease","volume":"4","author":"Foster","year":"2012","journal-title":"Nutrients"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jtemb.2006.01.006","article-title":"Zinc requirements and the risks and benefits of zinc supplementation","volume":"20","author":"Maret","year":"2006","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1079\/PHN2005724","article-title":"Use of national food balance data to estimate the adequacy of zinc in national food supplies: Methodology and regional estimates","volume":"8","author":"Wuehler","year":"2005","journal-title":"Public Health Nutr."},{"key":"ref_8","unstructured":"(2017, July 03). World Health Organization. Available online: http:\/\/www.who.int\/whr\/2002."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"327","DOI":"10.4161\/gmcr.1.5.14764","article-title":"Detection of genomic changes in transgenic Bt rice populations through genetic fingerprinting using amplified fragment length polymorphism (AFLP)","volume":"1","author":"Chandel","year":"2010","journal-title":"GM Crops"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ng913","article-title":"Identification of SLC39A4, a gene involved in acrodermatitis enteropathica","volume":"31","author":"Giraudet","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1093\/jn\/130.5.1388S","article-title":"Zinc deficiency, malnutrition and the gastrointestinal tract","volume":"130","author":"Wapnir","year":"2000","journal-title":"J. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1093\/jn\/137.1.135","article-title":"A mathematical model of zinc absorption in humans as a function of dietary zinc and phytate","volume":"137","author":"Miller","year":"2007","journal-title":"J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1146\/annurev.nu.05.070185.002013","article-title":"Clinical manifestations of zinc deficiency","volume":"5","author":"Prasad","year":"1985","journal-title":"Annu. Rev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1097\/MCO.0b013e3283312956","article-title":"Zinc: Role in immunity, oxidative stress and chronic inflammation","volume":"12","author":"Prasad","year":"2009","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1093\/jn\/114.10.1762","article-title":"Interference in the development of a secondary immune response in mice by zinc deprivation: Persistence of effects","volume":"114","author":"Fraker","year":"1984","journal-title":"J. Nutr."},{"key":"ref_16","first-page":"354","article-title":"The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: Explanation and elaboration","volume":"6","author":"Liberati","year":"2009","journal-title":"BMJ"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.ijsu.2010.02.007","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"8","author":"Moher","year":"2010","journal-title":"Int. J. Surg."},{"key":"ref_18","unstructured":"(2017, July 03). American Autoimmune Related Diseases Association. Available online: https:\/\/www.aarda.org\/diseaselist\/."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3109\/03009747809095662","article-title":"Trace elements in serum and urine of patients with rheumatoid arthritis","volume":"7","author":"Aaseth","year":"1978","journal-title":"Scand. J. Rheumatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ijd.12769","article-title":"Evaluation of serum zinc level in patients with newly diagnosed and resistant alopecia areata","volume":"55","author":"Atef","year":"2016","journal-title":"Int. J. Dermatol."},{"key":"ref_22","first-page":"195","article-title":"Bone mineral content, 25-hydroxycalciferol and zinc serum levels in insulin-dependent (type I) diabetic patients","volume":"21","author":"Arreola","year":"1990","journal-title":"Arch. Investig. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1136\/ard.41.5.458","article-title":"Serum copper and erythrocyte superoxide dismutase in rheumatoid arthritis","volume":"41","author":"Banford","year":"1982","journal-title":"Ann. Rheum. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/0378-6323.45216","article-title":"Trace element levels in alopecia areata","volume":"75","author":"Bhat","year":"2009","journal-title":"Indian J. Dermatol. Venereol. Leprol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1515\/JPEM.2005.18.10.1007","article-title":"Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus","volume":"18","author":"Bideci","year":"2005","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1023\/A:1009254424394","article-title":"Lack of acute zinc effects in glucose metabolism in healthy and insulin-dependent diabetes mellitus patients","volume":"12","author":"Figueiredo","year":"1999","journal-title":"Biometals"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1007\/BF02784618","article-title":"Zinc and copper in the serum of diabetic patients","volume":"32","author":"Car","year":"1992","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3109\/03009748709102508","article-title":"Serum aluminium concentrations in patients with rheumatoid arthritis","volume":"16","author":"Dijkmans","year":"1987","journal-title":"Scand. J. Rheumatol."},{"key":"ref_29","first-page":"541","article-title":"Zinc profiles in rheumatoid arthritis","volume":"8","author":"Peterson","year":"1990","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/ana.410140409","article-title":"Zinc in multiple sclerosis","volume":"14","author":"Catalanotto","year":"1983","journal-title":"Ann. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12011-008-8117-8","article-title":"Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism","volume":"123","author":"Erdal","year":"2008","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_32","first-page":"161","article-title":"High copper and low zinc serum levels in Iranian patients with multiple sclerosis: A case control study","volume":"58","author":"Ghazavi","year":"2012","journal-title":"Clin. Lab."},{"key":"ref_33","first-page":"88","article-title":"Prospective and retrospective studies of zinc concentrations in serum, blood clots, hair and urine in young patients with insulin-dependent diabetes mellitus","volume":"102","author":"Hallmans","year":"1983","journal-title":"Acta Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/03009747509095612","article-title":"The content of calcium, magnesium, copper, zinc, lead and chromium in the blood of patients with rheumatoid arthritis","volume":"4","author":"Hansson","year":"1975","journal-title":"Scand. J. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3109\/03009749209099216","article-title":"Nutrient intake and nutritional status in children with juvenile chronic arthritis","volume":"21","author":"Haugen","year":"1992","journal-title":"Scand. J. Rheumatol."},{"key":"ref_36","first-page":"637","article-title":"Dietary intake and serum concentrations of antioxidants in children with juvenile arthritis","volume":"18","author":"Helgeland","year":"2000","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1136\/ard.43.3.386","article-title":"Nutritional status in patients with rheumatoid arthritis","volume":"43","author":"Helliwell","year":"1984","journal-title":"Ann. Rheum. Dis."},{"key":"ref_38","first-page":"41","article-title":"Zinc, copper and magnesium status in insulin-dependent diabetes","volume":"26","author":"Isbir","year":"1994","journal-title":"Diabetes Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1016\/j.jnutbio.2011.09.008","article-title":"Disturbed zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of zinc","volume":"23","author":"Jansen","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"ref_40","first-page":"105","article-title":"Serum selenium, zinc, and copper in early diagnosed patients with pemphigus vulgaris","volume":"41","author":"Javanbakht","year":"2012","journal-title":"Iran J. Public Health"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.1600-0404.1989.tb03803.x","article-title":"Zinc, copper and magnesium concentration in serum and CSF of patients with neurological disorders","volume":"79","author":"Kapaki","year":"1989","journal-title":"Acta Neurol. Scand."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0009-8981(90)90229-L","article-title":"65 Zinc absorption in patients with insulin-dependent diabetes mellitus assessed by whole-body counting technique","volume":"189","author":"Kiilerich","year":"1990","journal-title":"Clin. Chim. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0009-8981(86)90082-3","article-title":"Distribution of serum zinc between albumin and alpha 2-macroglobulin in patients with different zinc metabolic disorders","volume":"154","author":"Kiilerich","year":"1986","journal-title":"Clin. Chim. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/j.1651-2227.1988.tb10739.x","article-title":"Early changes of some serum proteins and metals in diabetic children","volume":"77","author":"Kobbah","year":"1988","journal-title":"Acta Paediatr. Scand."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.clnu.2015.05.022","article-title":"Magnesium, zinc, and chromium levels in children, adolescents, and young adults with type 1 diabetes","volume":"35","author":"Lin","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_46","first-page":"121","article-title":"Serum levels of minerals and vitamins in two categories of female alopecia subjects using hair relaxer","volume":"29","author":"Iyanda","year":"2011","journal-title":"DSI"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1007\/BF01649424","article-title":"Zinc levels after intravenous administration of zinc sulphate in insulin-dependent diabetes mellitus patients","volume":"69","author":"Maldonado","year":"1991","journal-title":"Klin. Wochenschr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s12011-010-8952-2","article-title":"A pilot study on zinc levels in patients with rheumatoid arthritis","volume":"143","author":"Mierzecki","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.anl.2004.01.005","article-title":"Taste function in Sj\u00f6gren\u2019s syndrome patients with special reference to clinical tests","volume":"31","author":"Negoro","year":"2004","journal-title":"Auris Nasus Larynx"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.vph.2005.06.005","article-title":"Serum fibrillin-antifibrillin immune complexes among diabetic children","volume":"43","author":"Nicoloff","year":"2005","journal-title":"Vascul. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s12011-010-8826-7","article-title":"Effects of different medical treatments on serum copper, selenium and zinc levels in patients with rheumatoid arthritis","volume":"142","author":"Bulut","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1136\/jnnp.45.8.691","article-title":"Zinc and copper in multiple sclerosis","volume":"45","author":"Palm","year":"1982","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_53","first-page":"21","article-title":"Trace elements in blood cells of diabetic subjects","volume":"10","author":"Raz","year":"1989","journal-title":"Diabetes Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1177\/0961203314530792","article-title":"Association between serum trace element concentrations and the disease activity of systemic lupus erythematosus","volume":"23","author":"Sahebari","year":"2014","journal-title":"Lupus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/sj.ejcn.1601601","article-title":"Copper and zinc intake and serum levels in patients with juvenile rheumatoid arthritis","volume":"57","author":"Yanaguibashi","year":"2003","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s12011-016-0746-8","article-title":"Determination of Serum Trace Elements (Zn, Cu, and Fe) in Pakistani Patients with Rheumatoid Arthritis","volume":"175","author":"Ullah","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1111\/j.1365-4632.2011.04968.x","article-title":"Serum zinc and copper status in Iranian patients with pemphigus vulgaris","volume":"50","author":"Yazdanpanah","year":"2011","journal-title":"Int. J. Dermatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s10067-004-1028-y","article-title":"Trace elements and some extracellular antioxidant proteins levels in serum of patients with systemic lupus erythematosus","volume":"24","author":"Yilmaz","year":"2005","journal-title":"Clin. Rheumatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1007\/BF01450895","article-title":"Serum zinc and copper in active rheumatoid arthritis: Correlation with interleukin 1 beta and tumour necrosis factor alpha","volume":"17","author":"Zoli","year":"1998","journal-title":"Clin. Rheumatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3109\/01485018608986935","article-title":"Low plasma zinc and androgen in insulin-dependent diabetes mellitus","volume":"16","author":"Arreola","year":"1986","journal-title":"Arch. Androl."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0049-0172(90)90022-8","article-title":"Nutritional status and growth in juvenile heumatoid arthritis","volume":"20","author":"Bacon","year":"1990","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1136\/ard.39.4.329","article-title":"Plasma zinc and its relationship to clinical symptoms and drug treatment in rheumatoid arthritis","volume":"39","author":"Balogh","year":"1980","journal-title":"Ann. Rheum. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/ajcn\/38.5.706","article-title":"Zinc absorption in celiac disease and dermatitis herpetiformis: A test of small intestinal function","volume":"38","author":"Crofton","year":"1983","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/0026-0495(94)90016-7","article-title":"Hyperzincuria in individuals with insulin-dependent diabetes mellitus: Concurrent zinc status and the effect of high-dose zinc supplementation","volume":"43","author":"Cunningham","year":"1994","journal-title":"Metabolism"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1002\/ana.410200610","article-title":"Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis","volume":"20","author":"Ho","year":"1986","journal-title":"Ann. Neurol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3109\/03009747509165264","article-title":"Zinc: Its relationship to osteoporosis in rheumatoid arthritis","volume":"4","author":"Kennedy","year":"1975","journal-title":"Scand. J. Rheumatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1365-2796.1989.tb01353.x","article-title":"Plasma zinc concentrations during the first 2 years after diagnosis of insulin-dependent diabetes mellitus: A prospective study","volume":"226","author":"Melchior","year":"1989","journal-title":"J. Intern. Med."},{"key":"ref_68","first-page":"271","article-title":"Copper and zinc status in rheumatoid arthritis: Studies of plasma, erythrocytes, and urine, and their relationship to disease activity markers and pharmacological treatment","volume":"11","author":"Milanino","year":"1993","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"932","DOI":"10.2337\/diab.38.7.932","article-title":"Zinc-dependent low thymic hormone level in type I diabetes","volume":"38","author":"Mocchegiani","year":"1989","journal-title":"Diabetes"},{"key":"ref_70","first-page":"643","article-title":"Zinc metabolism in rheumatoid arthritis: Plasma and urinary zinc and relationship to disease activity","volume":"24","author":"Naveh","year":"1997","journal-title":"J. Rheumatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1590\/S0004-28032011000100013","article-title":"Research on zinc blood levels and nutritional status in adolescents with autoimmune hepatitis","volume":"48","author":"Pereira","year":"2011","journal-title":"Arq. Gastroenterol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/00006676-200104000-00012","article-title":"Evidence that diabetes mellitus favors impaired metabolism of zinc, copper, and selenium in chronic pancreatitis","volume":"22","author":"Quilliot","year":"2001","journal-title":"Pancreas"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0009-8981(93)90245-Y","article-title":"Magnesium, zinc and copper in plasma and blood cellular components in children with IDDM","volume":"215","author":"Rohn","year":"1993","journal-title":"Clin. Chim. Acta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/S0946-672X(98)80031-X","article-title":"Selenium, Zinc and Copper in Plasma of patients with Type 1 Diabetes Mellitus in Different Metabolic Control States","volume":"12","author":"Lagarda","year":"1998","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/ajcn\/50.1.136","article-title":"Trace element status in multiple sclerosis","volume":"50","author":"Smith","year":"1989","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF02784402","article-title":"Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis","volume":"68","author":"Tuncer","year":"1999","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1016\/j.metabol.2009.04.035","article-title":"Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus","volume":"58","author":"Krizko","year":"2009","journal-title":"Metabolism"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1385\/BTER:106:2:123","article-title":"Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis","volume":"106","author":"Yazar","year":"2005","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12011-012-9352-6","article-title":"Interaction between zinc, cadmium, and lead in scalp hair samples of Pakistani and Irish smokers rheumatoid arthritis subjects in relation to controls","volume":"148","author":"Afridi","year":"2012","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10661-015-4353-5","article-title":"Estimation of toxic elements in the samples of different cigarettes and their effect on the essential elemental status in the biological samples of Irish smoker rheumatoid arthritis consumers","volume":"187","author":"Afridi","year":"2015","journal-title":"Environ. Monit. Assess."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1385\/BTER:93:1-3:1","article-title":"Manganese, copper, and zinc in cerebrospinal fluid from patients with multiple sclerosis","volume":"93","author":"Larsen","year":"2003","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.jclinepi.2007.11.010","article-title":"Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry","volume":"61","author":"Peters","year":"2008","journal-title":"J. Clin. Epidemiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1093\/hmg\/10.25.2907","article-title":"Dissection of the HLA association with multiple sclerosis in the founder isolated population of Sardinia","volume":"10","author":"Marrosu","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1093\/hmg\/9.20.2967","article-title":"Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia","volume":"9","author":"Zavattari","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Pitzalis, M., Zavattari, P., Murru, R., Deidda, E., Zoledziewska, M., Murru, D., Moi, L., Motzo, C., Orr\u00f9, V., and Costa, G. (2008). Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia. BMC Med. Genet., 9.","DOI":"10.1186\/1471-2350-9-3"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2013.08.041","article-title":"Genetic variants regulating immune cell levels in health and disease","volume":"155","author":"Steri","year":"2013","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1056\/NEJMoa1610528","article-title":"Overexpression of the cytokine BAFF and autoimmunity risk","volume":"376","author":"Steri","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.2337\/diabetes.51.12.3573","article-title":"Sex-related bias and exclusion mapping of the nonrecombinant portion of chromosome Y in human type 1 diabetes in the isolated founder population of Sardinia","volume":"51","author":"Contu","year":"2002","journal-title":"Diabetes"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Monti, M.C., Guido, D., Montomoli, C., Sardu, C., Sanna, A., Pretti, S., Lorefice, L., Marrosu, M.G., Valera, P., and Cocco, E. (2016). Is Geo-Environmental Exposure a Risk Factor for Multiple Sclerosis? A Population-Based Cross-Sectional Studyin South-Western Sardinia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163313"},{"key":"ref_90","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_91","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nature11984","article-title":"Induction of pathogenic TH 17 cells by inducible salt-sensing kinase SGK1","volume":"496","author":"Wu","year":"2013","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1039\/c3mt00353a","article-title":"Multiple impacts of zinc on immune function","volume":"6","author":"Haase","year":"2014","journal-title":"Metallomics"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1086\/315916","article-title":"Effects of zinc deficiency on Th1 and Th2 cytokine shifts","volume":"182","author":"Prasad","year":"2000","journal-title":"J. Infect. Dis."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/imm.12536","article-title":"Inhibition of interleukin-1\u03b2-mediated interleukin-1 receptor-associated kinase 4 phosphorylation by zinc leads to repression of memory T helper type 17 response in humans","volume":"146","author":"Lee","year":"2015","journal-title":"Immunology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11786","DOI":"10.1073\/pnas.1323557111","article-title":"Zinc transporter SLC39A10\/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength","volume":"111","author":"Hojyo","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/mnfr.201500524","article-title":"Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures","volume":"60","author":"Rosenkranz","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jnutbio.2015.11.010","article-title":"Induction of regulatory T cells in Th1-\/Th17-driven experimental autoimmune encephalomyelitis by zinc administration","volume":"29","author":"Rosenkranz","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1093\/intimm\/dxq017","article-title":"Zinc suppresses Th17 development via inhibition of STAT3 activation","volume":"22","author":"Kitabayashi","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Bredholt, M., and Frederiksen, J.L. (2016). Zinc in multiple sclerosis: A systematic review and meta-analysis. ASN Neuro, 8.","DOI":"10.1177\/1759091416651511"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.nut.2017.03.009","article-title":"Dietary habits; concentration of copper, zinc, and Cu-to-Zn ratio in serum and ability status of patients with relapsing-remitting multiple sclerosis","volume":"39","author":"Socha","year":"2017","journal-title":"Nutrition"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s00401-017-1696-8","article-title":"Pathogenic implications of distinct patterns of iron and zinc in chronic MS lesions","volume":"134","author":"Popescu","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1385\/BTER:79:1:15","article-title":"Zinc inhibits the mixed lymphocyte culture","volume":"79","author":"Campo","year":"2001","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1038\/sj.bmt.1704509","article-title":"Zinc in pharmacological doses suppresses allogeneic reaction without affecting the antigenic response","volume":"33","author":"Faber","year":"2004","journal-title":"Bone Marrow Transpl."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S1053-2498(01)00384-9","article-title":"Zinc chloride-mediated reduction of apoptosis as an adjunct immunosuppressive modality in cardiac transplantation","volume":"21","author":"Kown","year":"2002","journal-title":"J. Heart Lung Transplant."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s10534-014-9786-8","article-title":"Oral zinc aspartate treats experimental autoimmune encephalomyelitis","volume":"27","author":"Schubert","year":"2014","journal-title":"Biometals"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1007\/s00125-010-1793-x","article-title":"Zinc, zinc transporters and diabetes","volume":"53","author":"Rungby","year":"2010","journal-title":"Diabetologia"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.jnutbio.2009.01.009","article-title":"Zinc and diabetes\u2014Clinical links and molecular mechanisms","volume":"20","author":"Jansen","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.2337\/db09-0551","article-title":"Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes\u2013associated variants","volume":"58","author":"Nicolson","year":"2009","journal-title":"Diabetes"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"14872","DOI":"10.1073\/pnas.0906587106","article-title":"Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice","volume":"106","author":"Lemaire","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1007\/s00125-010-1733-9","article-title":"Beta cell-specific ZnT8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion","volume":"53","author":"Wijesekara","year":"2010","journal-title":"Diabetologia"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6843","DOI":"10.1073\/pnas.0502257102","article-title":"Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response","volume":"102","author":"Liuzzi","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s00011-016-1003-5","article-title":"Hepatic mobilization of zinc after an experimental surgery, and its relationship with inflammatory cytokines release, and expression of metallothionein and Zip14 transporter","volume":"66","author":"Brambila","year":"2017","journal-title":"Inflamm. Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bonaventura, P., Lamboux, A., Albar\u00e8de, F., and Miossec, P. (2016). A Feedback Loop between Inflammation and Zn Uptake. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147146"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1177\/153537020422901002","article-title":"DNA methylation, cancer susceptibility, and nutrient interactions","volume":"229","author":"Davis","year":"2004","journal-title":"Exp. Biol. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/bdrb.20264","article-title":"Zinc and reproduction: Effects of zinc deficiency on prenatal and early postnatal development","volume":"89","author":"Keen","year":"2010","journal-title":"Birth Defects Res. B Dev. Reprod. Toxicol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1126\/science.7123244","article-title":"Gestational zinc deprivation in mice: Persistence of immunodeficiency for three generations","volume":"218","author":"Beach","year":"1982","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1152\/ajpregu.00050.2008","article-title":"Moderate zinc restriction during fetal and postnatal growth of rats: Effects on adult arterial blood pressure and kidney","volume":"295","author":"Tomat","year":"2008","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10653-013-9520-4","article-title":"A correlation study between multiple sclerosis and type 1 diabetes incidences and geochemical data in Europe","volume":"36","author":"Valera","year":"2014","journal-title":"Environ. Geochem. Health"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Valera, P., Zavattari, P., Sanna, A., Pretti, S., Marcello, A., Mannu, C., Targhetta, C., Bruno, G., and Songini, M. (2015). Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141262"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.gexplo.2010.06.004","article-title":"Hydrogeochemical analysis on Italian bottled mineral waters: Effects of geology","volume":"107","author":"Dinelli","year":"2010","journal-title":"J. Geochem. Explor."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.gexplo.2010.04.004","article-title":"Trace elements and ions in Italian bottled mineral waters: Identification of anomalous values and human health related effects","volume":"107","author":"Cicchella","year":"2010","journal-title":"J. Geochem. Explor."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.gexplo.2011.11.002","article-title":"Comparative study between bottled mineral and tap water in Italy","volume":"112","author":"Dinelli","year":"2012","journal-title":"J. Geochem. Explor."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.gexplo.2011.07.009","article-title":"Major and trace elements in tap water from Italy","volume":"112","author":"Dinelli","year":"2012","journal-title":"J. Geochem. Explor."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.jafrearsci.2014.07.017","article-title":"Impact of mine tailings on surrounding soils and ground water: Case of Kettara old mine, Morocco","volume":"100","author":"Valera","year":"2014","journal-title":"J. Afr. Earth Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"567","DOI":"10.3109\/15622975.2015.1062551","article-title":"Relationships of local lithium concentrations in drinking water to regional suicide rates in Italy","volume":"16","author":"Pompili","year":"2015","journal-title":"World J. Biol. Psychiatry"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.psychres.2017.01.041","article-title":"Arsenic: Association of regional concentrations in drinking water with suicide and natural causes of death in Italy","volume":"249","author":"Pompili","year":"2017","journal-title":"Psychiatry Res."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1144\/geochem2011-096","article-title":"The geochemistry of niobium and its distribution and relative mobility in agricultural soils of Europe","volume":"12","author":"Scheib","year":"2012","journal-title":"Geochem. Explor. Environ. A"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1144\/geochem2014-279","article-title":"Mobile metal ion\u00ae analysis of european agricultural soils: Bioavailability, weathering, Geogenic patterns and anthropogenic anomalies","volume":"15","author":"Mann","year":"2015","journal-title":"Geochem. Explor. Environ. A"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemgeo.2014.12.004","article-title":"Geochemical fingerprinting and source discrimination of agricultural soils at continental scale","volume":"396","author":"Sadeghi","year":"2015","journal-title":"Chem. Geol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.gexplo.2014.11.020","article-title":"GEMAS: Indium in agricultural and grazing land soil of Europe\u2014Its source and geochemical distribution patterns","volume":"154","author":"Ladenberger","year":"2015","journal-title":"J. Geochem. Explor."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.apgeochem.2016.08.014","article-title":"The GEMAS Project Team. Use of GEMAS data for risk assessment of cadmium in European agricultural and grazing land soil under the REACH Regulation","volume":"74","author":"Birke","year":"2016","journal-title":"Appl. Geochem."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.gexplo.2016.11.007","article-title":"GEMAS: Cadmium distribution and its sources in agricultural and grazing land soil of Europe\u2014Original data versus clr-transformed data","volume":"173","author":"Birke","year":"2017","journal-title":"J. Geochem. Explor."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/bor.12029","article-title":"Geochemical evidence of aeolian deposits in European soils","volume":"43","author":"Scheib","year":"2014","journal-title":"Boreas"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/1\/68\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:50:51Z","timestamp":1760194251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/10\/1\/68"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,11]]},"references-count":133,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,1]]}},"alternative-id":["nu10010068"],"URL":"https:\/\/doi.org\/10.3390\/nu10010068","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,11]]}}}