Complement factor h autoantibodies and age-related macular degeneration.
OBJECTIVE
In this case-control study, the hypothesis that factor H autoantibodies are associated with age-related macular degeneration (AMD) was examined.


METHODS
One hundred AMD patients (median age, 78 years), 98 age-matched control subjects (median age, 78 years) known not to have AMD, and 100 healthy blood donors (median age, 43 years) were enrolled. An enzyme-linked immunosorbent assay (ELISA) was used to screen for complement factor H autoantibodies and either quantitative polymerase chain reaction (qPCR) or multiplex ligation-dependent probe amplification (MLPA) were performed to measure the copy number of the gene encoding complement factor H-related protein 3 (CFHR3).


RESULTS
There was a significant difference in the median complement factor H autoantibody titer between the three groups (AMD patients, 196 reference units [RU]]; age-match control subjects, 316 RU; and blood donor control subjects, 121 RU; Kruskal-Wallis test, P < 0.001). Pair-wise comparison (Mann-Whitney test) showed that all three groups were significantly different from each other. Two different thresholds were used in the healthy blood donors to identify individuals with complement factor H autoantibodies. Both suggested that the prevalence of factor H autoantibodies was decreased in AMD patients. The CFHR3 copy number was measured as a surrogate for the deletion of the genes encoding complement factor H-related proteins 3 and 1 (CFHR3/1). The allele frequency of the deletion was significantly higher in the age-matched control subjects than in the AMD patients (22.2% vs. 8.2%).


CONCLUSIONS
The level of factor H autoantibodies is lower in AMD patients than in age-matched control subjects.
Dhillon
Baljean
B
Department of Clinical and Surgical Sciences, Princess Alexandra Eye Pavilion.
Wright
Alan F
AF
Tufail
Adnan
A
Pappworth
Isabel
I
Hayward
Caroline
C
Moore
Iain
I
Strain
Lisa
L
Kavanagh
David
D
Barlow
Paul N
PN
Herbert
Andrew P
AP
Schmidt
Christoph Q
CQ
Armbrecht
Ana-Maria
AM
Laude
Augustinus
A
Deary
Ian J
IJ
Staniforth
Scott J
SJ
Holmes
Lucy V
LV
Goodship
Timothy H J
TH
Marchbank
Kevin J
KJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D001782:Blood Donors; D001798:Blood Proteins / Q000235:genetics; D016022:Case-Control Studies; D003180:Complement C3b Inactivator Proteins / Q000235:genetics; D017242:Complement Factor H / Q000276:immunology; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D006801:Humans; D008268:Macular Degeneration / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D016133:Polymerase Chain Reaction; D055815:Young Adult
D001323:Autoantibodies; D001798:Blood Proteins; C493495:CFH protein, human; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D017931:DNA Primers; D015342:DNA Probes; D017242:Complement Factor H