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Measurement of factor H variants in plasma using variant-specific monoclonal antibodies: application to assessing risk of age-related macular degeneration.

Abstract：

PURPOSE:The Y402H polymorphism in the complement regulator factor H (fH) is strongly associated with age-related macular degeneration (AMD) across diverse populations. Persons homozygous for histidine at this position have up to 12-fold greater risk for AMD than those homozygous for tyrosine. Knowledge of fH-Y402H status is, therefore, valuable in predicting risk and focusing preventive measures in the elderly. This knowledge requires genetic analysis, which is unavailable in most laboratories and which provides no information about the levels of fH protein, a putative linked determinant of disease risk. METHODS:The authors describe novel monoclonal antibodies that distinguish the two fH allelic variants in plasma. ELISA with these antibodies not only reliably identifies the fH-Y402H status, confirmed by genotyping, but also quantifies the concentration of total fH and the fH-Y402 and fH-H402 variants. RESULTS:In young adult control subjects, mean fH concentration was 233 mg/L. In elderly control subjects, mean fH concentration was 269 mg/L, whereas in a matching AMD cohort, mean fH concentration was 288 mg/L. Total fH concentration was similar in each subgroup of young and elderly control subjects; however, in the AMD group, fH concentration was significantly higher in the heterozygous subgroup. Measurement of the two variants in this subgroup showed that both were elevated to a similar degree. CONCLUSIONS:The novel monoclonal antibody MBI-7 was used to develop a robust assay for measurement of fH and the variants in plasma. The simplicity of the assay means that it may be used by any clinical laboratory to identify polymorphic status and to quantify plasma levels in persons at risk for AMD.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Hakobyan S,Harris CL,Tortajada A,Goicochea de Jorge E,García-Layana A,Fernández-Robredo P,Rodríguez de Córdoba S,Morgan BP

doi

10.1167/iovs.07-1523

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1983-90

issue

eissn

0146-0404

issn

1552-5783

pii

49/5/1983

journal_volume

pub_type

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Measurement of factor H variants in plasma using variant-specific monoclonal antibodies: application to assessing risk of age-related macular degeneration.