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dc.contributor.authorLay, Elizabethen
dc.contributor.authorNutland, Sarahen
dc.contributor.authorSmith, Julia Een
dc.contributor.authorHiles, Ianen
dc.contributor.authorSmith, RIchard AGen
dc.contributor.authorSeilly, David Jen
dc.contributor.authorBuchberger, Annaen
dc.contributor.authorSchwaeble, Wilhelmen
dc.contributor.authorLachmann, Sir Peteren
dc.date.accessioned2014-10-09T10:05:14Z
dc.date.available2014-10-09T10:05:14Z
dc.date.issued2014-08-13en
dc.identifier.citationClinical & Experimental Immunology 181(2):314-22. doi: 10.1111/cei.12437.en
dc.identifier.issn0009-9104
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246146
dc.description.abstractSera from a large panel of normal subjects were typed for three common polymorphisms, one in C3 (R102G) and two in Factor H (V62I and Y402H) that influence predisposition to age related macular degeneration and to some forms of kidney disease. Three groups of sera were tested; those that were homozygous for the three risk alleles; those that were heterozygous for all three; and those homozygous for the low risk alleles. These groups vary in their response to the addition of exogenous Factor I when the alternative complement pathway is activated by zymosan. Both the reduction in the maximum amount of iC3b formed and the rate at which the iC3b is converted to C3dg are affected. For both reactions the at-risk complotype requires higher doses of Factor I to produce similar down-regulation. Since iC3b reacting with the complement receptor CR3 is a major mechanism by which complement activation gives rise to inflammation the breakdown of iC3b to C3dg can be seen to have major significance for reducing complement induced inflammation. These findings demonstrate for the first time that sera from subjects with different complement alleles do behave as predicted in an in-vitro assay of the down-regulation of the alternative complement pathway by increasing the concentration of Factor I. These results support the hypothesis that exogenous Factor I may be a valuable therapeutic for down-regulating hyperactivity of the C3b feedback cycle and thereby providing a treatment for age-related macular degeneration and other inflammatory diseases of later life.
dc.languageEnglishen
dc.language.isoenen
dc.publisherWiley
dc.titleComplotype affects the extent of down-regulation by Factor I of the C3b feedback cycle in-vitroen
dc.typeArticle
dc.description.versionThis is the author's accepted manuscript and will be under embargo until the 13th of August 2015. This final version is available from Wiley in Clinical & Experimental Immunology at http://onlinelibrary.wiley.com/doi/10.1111/cei.12437/abstract.en
prism.endingPage322
prism.publicationDate2014en
prism.publicationNameClinical & Experimental Immunologyen
prism.startingPage314
prism.volume181en
dc.rioxxterms.funderGlaxoSmithKline
dcterms.dateAccepted2014-08-11en
rioxxterms.versionofrecord10.1111/cei.12437en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-08-13en
dc.contributor.orcidLachmann, Sir Peter [0000-0003-2849-3524]
dc.identifier.eissn1365-2249
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2015-08-13


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