Systemic complement activation levels in Stargardt disease.

<h4>Purpose</h4>Preclinical 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 bee...

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Autores principales:	Patty P A Dhooge, Esmee H Runhart, Catherina H Z Li, Corrie M de Kat Angelino, Carel B Hoyng, Renate G van der Molen, Anneke I den Hollander
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/250ba005364d4e1da67bbeaf7cbb86e0
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spelling	oai:doaj.org-article:250ba005364d4e1da67bbeaf7cbb86e02021-12-02T20:09:58ZSystemic complement activation levels in Stargardt disease.1932-620310.1371/journal.pone.0253716https://doaj.org/article/250ba005364d4e1da67bbeaf7cbb86e02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253716https://doaj.org/toc/1932-6203<h4>Purpose</h4>Preclinical 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.<h4>Methods</h4>Systemic 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).<h4>Results</h4>The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3-15%). 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's Correlation).<h4>Conclusions</h4>Systemic 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.Patty P A DhoogeEsmee H RunhartCatherina H Z LiCorrie M de Kat AngelinoCarel B HoyngRenate G van der MolenAnneke I den HollanderPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0253716 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Patty P A Dhooge Esmee H Runhart Catherina H Z Li Corrie M de Kat Angelino Carel B Hoyng Renate G van der Molen Anneke I den Hollander Systemic complement activation levels in Stargardt disease.
description	<h4>Purpose</h4>Preclinical 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.<h4>Methods</h4>Systemic 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).<h4>Results</h4>The C3d/C3 ratio did not significantly differ between patients (mean C3d/C3 ratio 3.5±1.4) and controls (mean C3d/C3 ratio 3.6±1.0), mean difference -0.156 (p = 0.804, independent samples t-test). The overall effect size was 8% (95% confidence interval, 3-15%). 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's Correlation).<h4>Conclusions</h4>Systemic 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.
format	article
author	Patty P A Dhooge Esmee H Runhart Catherina H Z Li Corrie M de Kat Angelino Carel B Hoyng Renate G van der Molen Anneke I den Hollander
author_facet	Patty P A Dhooge Esmee H Runhart Catherina H Z Li Corrie M de Kat Angelino Carel B Hoyng Renate G van der Molen Anneke I den Hollander
author_sort	Patty P A Dhooge
title	Systemic complement activation levels in Stargardt disease.
title_short	Systemic complement activation levels in Stargardt disease.
title_full	Systemic complement activation levels in Stargardt disease.
title_fullStr	Systemic complement activation levels in Stargardt disease.
title_full_unstemmed	Systemic complement activation levels in Stargardt disease.
title_sort	systemic complement activation levels in stargardt disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/250ba005364d4e1da67bbeaf7cbb86e0
work_keys_str_mv	AT pattypadhooge systemiccomplementactivationlevelsinstargardtdisease AT esmeehrunhart systemiccomplementactivationlevelsinstargardtdisease AT catherinahzli systemiccomplementactivationlevelsinstargardtdisease AT corriemdekatangelino systemiccomplementactivationlevelsinstargardtdisease AT carelbhoyng systemiccomplementactivationlevelsinstargardtdisease AT renategvandermolen systemiccomplementactivationlevelsinstargardtdisease AT annekeidenhollander systemiccomplementactivationlevelsinstargardtdisease
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Systemic complement activation levels in Stargardt disease.

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