{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:41:57Z","timestamp":1789839717669,"version":"4.0.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymatic disorder that is particularly prevalent in Africa, Asia, and the Middle East. This study aimed to assess the long-term health risks associated with G6PD deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A retrospective cohort study was conducted using data from a national healthcare provider in Israel (Leumit Health Services). A total of 7,473 G6PD-deficient individuals were matched with 29,892 control subjects in a 1:4 ratio, based on age, gender, socioeconomic status, and ethnic groups. The exposure of interest was recorded G6PD diagnosis or positive G6PD diagnostic test. The main outcomes and measures included rates of infectious diseases, allergic conditions, and autoimmune disorders between 2002 and 2022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significantly increased rates were observed for autoimmune disorders, infectious diseases, and allergic conditions in G6PD-deficient individuals compared to the control group. Specifically, notable increases were observed for rheumatoid arthritis (odds ratio [OR] 2.41, p&amp;lt;0.001), systemic lupus erythematosus (OR 4.56, p&amp;lt;0.001), scleroderma (OR 6.87, p&amp;lt;0.001), pernicious anemia (OR 18.70, p&amp;lt;0.001), fibromyalgia (OR 1.98, p&amp;lt;0.001), Graves\u2019 disease (OR 1.46, p=0.001), and Hashimoto\u2019s thyroiditis (OR 1.26, p=0.001). These findings were supported by elevated rates of positive autoimmune serology and higher utilization of medications commonly used to treat autoimmune conditions in the G6PD-deficient group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, individuals with G6PD deficiency are at a higher risk of developing autoimmune disorders, infectious diseases, and allergic conditions. This large-scale observational study provides valuable insights into the comprehensive association between G6PD deficiency and infectious and immune-related diseases. The findings emphasize the importance of considering G6PD deficiency as a potential risk factor in clinical practice and further research is warranted to better understand the underlying mechanisms of these associations.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1232560","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T11:07:30Z","timestamp":1694430450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Glucose-6-phosphate dehydrogenase deficiency and long-term risk of immune-related disorders"],"prefix":"10.3389","volume":"14","author":[{"given":"Ariel","family":"Israel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro A.","family":"Sch\u00e4ffer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matitiahu","family":"Berkovitch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Ozeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Merzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilan","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avivit","family":"Golan-Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eytan","family":"Ruppin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Vinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eli","family":"Magen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/S0140-6736(08)60073-2","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"371","author":"Cappellini","year":"2008","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2015.11.006","article-title":"Glucose-6-phosphate dehydrogenase deficiency","volume":"30","author":"Luzzatto","year":"2016","journal-title":"Hematol Oncol Clin North Am"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2008.12.005","article-title":"The global prevalence of glucose-6-phosphate dehydrogenase deficiency: A systematic review and meta-analysis","volume":"42","author":"Nkhoma","year":"2009","journal-title":"Blood Cells Mol Dis"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/376246a0","article-title":"Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria","volume":"376","author":"Ruwende","year":"1995","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061573","article-title":"Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance","volume":"293","author":"Tishkoff","year":"2001","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V84.11.3613.bloodjournal84113613","article-title":"G6PD deficiency","volume":"84","author":"Beutler","year":"1994","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1159\/000153257","article-title":"Distribution of serum proteins, red cell enzymes and haemoglobins in vitiligo","volume":"32","author":"Saha","year":"1982","journal-title":"Hum Hered"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/IJERPH20032709","article-title":"Is glucose-6-phosphate dehydrogenase deficiency a risk factor for autoimmune thyroid disease? 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