The role of anti-complement factor H antibodies in the development of atypical haemolytic uremic syndrome: a possible contribution to abnormality of platelet function.

Published on Apr 1, 2020in British Journal of Haematology6.998
· DOI :10.1111/BJH.16297
Madoka Fujisawa3
Estimated H-index: 3
(UTokyo: University of Tokyo),
Atsushi Yasumoto14
Estimated H-index: 14
(UTokyo: University of Tokyo)
+ 4 AuthorsMasaomi Nangaku84
Estimated H-index: 84
(UTokyo: University of Tokyo)
Atypical haemolytic uremic syndrome (aHUS) is associated with complement system abnormality, such as production of complement factor H (CFH) autoantibodies. The growing evidence indicates complement overactivation on platelets is intimately involved in aHUS pathogenesis, besides endothelial injury. We here showed plasma from patients with anti-CFH antibodies induced aggregation of washed platelets, while purified anti-CFH antibodies suppressed aggregation. This suggested anti-CFH antibody itself suppressed thrombosis, while other plasma factor including complement factors could overactivate the platelets, leading to aggregation, which augmented the notion the state of complement activation influenced by anti-CFH antibodies is important in the aggregation of platelets in aHUS.
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Uncontrolled activation of the complement system against endothelial and blood cells is central to the pathogenesis of atypical hemolytic uremic syndrome (aHUS). aHUS patients frequently carry mutations in the inhibitory complement regulator factor H (FH). Mutations cluster in domains 19 and 20 (FH19-20), which are critical for recognizing self surfaces. On endothelial cells, binding of FH is generally attributed to heparan sulfate. This theory, however, is questioned by the puzzling observation...
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