Systemic Complement Activation in Age-Related Macular Degeneration
Publication Date
July 02, 2008
Journal
PLOS ONE
Authors
Hendrik P. N. Scholl, Peter Charbel Issa, Maja Walier, Stefanie Janzer, et al
Volume
3
Issue
7
Pages
e2593
DOI
https://dx.plos.org/10.1371/journal.pone.0002593
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0002593
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/18596911
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440421
Europe PMC
http://europepmc.org/abstract/MED/18596911
Web of Science
000263288200052
Scopus
49749150467
Mendeley
http://www.mendeley.com/research/systemic-complement-activation-agerelated-macular-degeneration-2
Events
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Mendeley | Further Information

{"title"=>"Systemic Complement Activation in Age-Related Macular Degeneration", "type"=>"journal", "authors"=>[{"first_name"=>"Hendrik P. N.", "last_name"=>"Scholl"}, {"first_name"=>"Peter Charbel", "last_name"=>"Issa"}, {"first_name"=>"Maja", "last_name"=>"Walier"}, {"first_name"=>"Stefanie", "last_name"=>"Janzer"}, {"first_name"=>"Beatrix", "last_name"=>"Pollok-Kopp"}, {"first_name"=>"Florian", "last_name"=>"Börncke"}, {"first_name"=>"Lars G.", "last_name"=>"Fritsche"}, {"first_name"=>"Ngaihang V.", "last_name"=>"Chong"}, {"first_name"=>"Rolf", "last_name"=>"Fimmers"}, {"first_name"=>"Thomas", "last_name"=>"Wienker"}, {"first_name"=>"Frank G.", "last_name"=>"Holz"}, {"first_name"=>"Bernhard H. F.", "last_name"=>"Weber"}, {"first_name"=>"Martin", "last_name"=>"Oppermann"}], "year"=>2008, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"49749150467", "issn"=>"1932-6203", "doi"=>"10.1371/journal.pone.0002593", "pmid"=>"18596911", "isbn"=>"2005512036", "pui"=>"352180429"}, "id"=>"b2193bd3-6859-3708-a18f-16573a3d4fbe", "abstract"=>"Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH), factor B-C2 (BF-C2) and complement C3 (C3) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.", "link"=>"http://www.mendeley.com/research/systemic-complement-activation-agerelated-macular-degeneration-2", "reader_count"=>61, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>18, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>5, "Student > Master"=>5, "Other"=>4, "Student > Bachelor"=>7, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>18, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>5, "Student > Master"=>5, "Other"=>4, "Student > Bachelor"=>7, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>6, "Mathematics"=>1, "Medicine and Dentistry"=>24, "Agricultural and Biological Sciences"=>24, "Psychology"=>2, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>24}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>24}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>6}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "Germany"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/927799"], "description"=>"*<p>AMD patients were categorized into mutually exclusive groups: All subjects classified as “early AMD” (n = 9) had extensive intermediate and/or large drusen in at least one eye and all qualified as category III of the Age-Related Eye Disease Study group. Patients with GA in both eyes or GA in one eye in the absence of CNV in the fellow eye were classified as “GA” (n = 25). Nineteen of these had subfoveal GA in at least one eye; the remaining six patients exclusively showed extrafoveal GA. If a CNV due to AMD was present in at least one eye, patients were classified as “CNV” (n = 78). Subjects with changes such as many hard drusen and/or pigmentary alterations in both eyes were excluded as these changes may refer to normal aging processes not necessarily linked to AMD.</p><p>** Difference between cases and controls, p = 0.02; <sup>***</sup> p<0.001.</p>", "links"=>[], "tags"=>["genetics and genomics/genetics of disease", "immunology/innate immunity", "ophthalmology/inherited eye disorders", "ophthalmology/macular disorders"], "article_id"=>598238, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002593.t001", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Clinical_and_Demographic_Characteristics_of_the_Study_Population_/598238", "title"=>"Clinical and Demographic Characteristics of the Study Population.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-02 02:17:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/927594"], "description"=>"<p>Complement gene SNPs (boxed with dotted lines) and protein plasma concentrations (boxed with solid lines) were determined in all AMD patients and controls. C3, C4 and factor B are substrates (open rectangles), factor H and factor D are regulators (open ellipses), Ba, C3d and SC5b-9 are markers of chronic activation (filled rectangles), and C3a and C5a are markers of acute activation (filled ellipses) of the alternative complement pathway.</p>", "links"=>[], "tags"=>["pathway", "polymorphic", "variants", "complement", "proteins"], "article_id"=>598025, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002593.g001", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Alternative_Pathway_of_Complement_Polymorphic_Variants_and_Complement_Proteins_under_Study_/598025", "title"=>"The Alternative Pathway of Complement: Polymorphic Variants and Complement Proteins under Study.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-07-02 02:13:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/927905"], "description"=>"*<p>Complement proteins in this table are arranged in groups of substrates (C3, C4, factor B), regulators (factor H, factor D), markers of acute (C3a, C5a) and chronic activation (Ba, C3d, SC5b-9) of the alternative pathway of complement (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002593#pone-0002593-g001\" target=\"_blank\">Fig. 1</a>).</p>**<p>Wilcoxon rank-sum test; corrected for multiple testing by Bonferroni-Holm procedure.</p>", "links"=>[], "tags"=>["concentrations", "complement", "proteins", "amd", "patients"], "article_id"=>598342, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002593.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_Concentrations_of_Complement_Proteins_in_AMD_Patients_and_Controls_/598342", "title"=>"Plasma Concentrations of Complement Proteins in AMD Patients and Controls.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-02 02:19:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/927854"], "description"=>"<p>Plasma Concentrations (mean±S.E.M.) of Complement Proteins in Carriers of Risk-Conferring and Protective Haplotypes of the <i>CFH</i> Gene.</p>", "links"=>[], "tags"=>["concentrations", "complement", "proteins", "carriers", "risk-conferring", "haplotypes"], "article_id"=>598288, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002593.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plasma_Concentrations_mean_S_E_M_of_Complement_Proteins_in_Carriers_of_Risk_Conferring_and_Protective_Haplotypes_of_the_CFH_Gene_/598288", "title"=>"Plasma Concentrations (mean±S.E.M.) of Complement Proteins in Carriers of Risk-Conferring and Protective Haplotypes of the <i>CFH</i> Gene.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2008-07-02 02:18:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/927702"], "description"=>"<p>Receiver operating characteristic curves for genetic markers (dotted line; A473A of <i>CFH</i>, IVS 10 of <i>BF-C2</i> and R102G of <i>C3</i>) and complement protein markers (solid line; Ba, C3d, and factor D) are shown. AUC = Area under ROC curve.</p>", "links"=>[], "tags"=>["curves", "discriminative", "markers", "complement"], "article_id"=>598137, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0002593.g002", "stats"=>{"downloads"=>3, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Receiver_Operating_Characteristic_ROC_Curves_for_the_Discriminative_Capability_of_Genetic_and_Protein_markers_of_the_Complement_System_/598137", "title"=>"Receiver Operating Characteristic (ROC) Curves for the Discriminative Capability of Genetic and Protein markers of the Complement System.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-07-02 02:15:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/457339", "https://ndownloader.figshare.com/files/457387", "https://ndownloader.figshare.com/files/457447"], "description"=>"<div><p>Dysregulation of the alternative pathway (AP) of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112) and controls (n = 67). Subjects were analyzed for single nucleotide polymorphisms in factor H (<em>CFH</em>), factor B-C2 (<em>BF-C2</em>) and complement C3 (<em>C3</em>) genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001), were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with <em>CFH</em> haplotypes.</p><p>This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of <em>CFH</em> that were previously linked to AMD susceptibility.</p></div>", "links"=>[], "tags"=>["systemic", "complement", "activation", "age-related", "macular", "degeneration"], "article_id"=>150084, "categories"=>["Immunology", "Medicine", "Genetics"], "users"=>["Hendrik P. N. Scholl", "Peter Charbel Issa", "Maja Walier", "Stefanie Janzer", "Beatrix Pollok-Kopp", "Florian Börncke", "Lars G. Fritsche", "Ngaihang V. Chong", "Rolf Fimmers", "Thomas Wienker", "Frank G. Holz", "Bernhard H. F. Weber", "Martin Oppermann"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0002593.s001", "https://dx.doi.org/10.1371/journal.pone.0002593.s002", "https://dx.doi.org/10.1371/journal.pone.0002593.s003"], "stats"=>{"downloads"=>13, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Systemic_Complement_Activation_in_Age_Related_Macular_Degeneration/150084", "title"=>"Systemic Complement Activation in Age-Related Macular Degeneration", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-07-02 00:01:24"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"25", "full-text"=>"33", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"3", "cited-by"=>"1", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"26", "full-text"=>"28", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"10", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"10", "full-text"=>"10", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"25", "full-text"=>"31", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"19", "full-text"=>"22", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}

Relative Metric

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