{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T02:14:03Z","timestamp":1784772843766,"version":"3.55.0"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["PPA-0517-0717-RAD"],"award-info":[{"award-number":["PPA-0517-0717-RAD"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\nPurpose<\/jats:title>\nPreclinical research provides evidence for the complement system as a potential common pathway in Stargardt disease (STGD1) and age-related macular degeneration (AMD) leading to retinal pigment epithelium (RPE) loss. However, systemic complement activation has not yet been assessed in STGD1 patients. We conducted a cross-sectional case-control study to assess systemic complement activation in STGD1 patients and its association with disease severity.<\/jats:p>\n<\/jats:sec>\n\nMethods<\/jats:title>\nSystemic concentrations of complement component C3 and its degradation product C3d were compared between 80 STGD1 patients and 80 controls that were frequency matched for age and sex. The C3d\/C3 ratio was used as parameter of systemic complement activation. Within the STGD1 cohort, we additionally examined the association between the C3d\/C3 ratio, demographic and behavioural factors (age, sex, smoking and BMI), and measures of disease severity (age at onset, visual acuity, and area of atrophy).<\/jats:p>\n<\/jats:sec>\n\nResults<\/jats:title>\nThe C3d\/C3 ratio did not significantly differ between patients (mean C3d\/C3 ratio 3.5\u00b11.4) and controls (mean C3d\/C3 ratio 3.6\u00b11.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3\u201315%). Elevated C3d\/C3 ratios (>8.1) were found in three patients who all had a concomitant inflammatory condition at the time of blood draw. Within the patient cohort, C3 levels were associated with sex (mean difference -134, p = 0.001, independent samples t-test) and BMI (correlation coefficient 0.463, p<0.001, Spearman\u2019s Correlation).<\/jats:p>\n<\/jats:sec>\n\nConclusions<\/jats:title>\nSystemic complement levels were not elevated in STGD1 patients compared to age and sex matched controls and was not associated with STGD1 severity. Considering the continued absent proof of a systemic contribution of the complement system to RPE loss in STGD1 patients, we hypothesize that complement activation in STGD1 is more likely a local process. In light of upcoming complement-targeted therapies, further studies are needed that measure complement levels in the eye of STGD1 patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0253716","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T17:31:09Z","timestamp":1624642269000},"page":"e0253716","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Systemic complement activation levels in Stargardt disease"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-1668","authenticated-orcid":true,"given":"Patty P. A.","family":"Dhooge","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmee H.","family":"Runhart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherina H. 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