Author: Willrich, Maria Alice V. ; Green, Dolly F. ; Aslam, Nabeel ; Avila-Casado, Carmen ; Rizk, Dana V. ; Li, Tingting ; Hladunewich, Michelle ; Radhakrishnan, Jay ; Juncos, Luis A. ; Lieske, John C. ; Philibert, David ; Sussman, Amy N. ; Gipson, Debbie S. ; Jefferson, Jonathan A. ; Erickson, Stephen B. ; Sethi, Amit ; Reich, Heather N. ; Brenchley, Paul ; Lafayette, Richard A. ; Beanlands, Heather ; Barbour, Sean J. ; McCarthy, Ellen T. ; Cattran, Daniel C. ; Parikh, Samir V. ; Leung, Nelson ; Beara-Lasic, Lada ; Fervenza, Fernando C. ; Gipson, Patrick E. ; Simon, James F. ; Appel, Gerald B. ; Canetta, Pietro A. ; Thomas, Lesley F. ; Sethi, Sanjeev ; Sedor, John R. ; Hebert, Lee A. ; Miao, Jing ; Rovin, Brad H. ; Frinack, Jody L. ; Blumenthal, Samuel S.

This article deals about limited significance of antifactor H antibodies in patients with membranous nephropathy.Limited significance of antifactor H antibodies in patients with membranous nephropathy.Large amounts of complement proteins are present in glomeruli of patients with membranous nephropathy, suggested that complement proteins in membranous nephropathy.Results above cutoff of 18.8 U/mL were considered pos. and anti-PLA2R was also tested using ELISA assay and >20 U/mL was defined as pos.Our study confirms that anti-CFH antibodies are present in a small subset of patients with membranous nephropathy, but prevalence is low.On the basis of our data, evaluating every patient with membranous nephropathy for anti-CFH antibody in routine laboratory testing is not warranted at this time.

01 Nov 2020·Journal of Extracellular VesiclesQ2 · MEDICINE

Tumour extracellular vesicle‐derived Complement Factor H promotes tumorigenesis and metastasis by inhibiting complement‐dependent cytotoxicity of tumour cells

Q2 · MEDICINE

ArticleOA

Author: Yam, Judy Wai Ping ; Mao, Xiaowen ; Zhou, Longyin ; Fung, Yi Man Eva ; Tey, Sze Keong ; Patz, Edward F. ; Liu, Bonnie Hei Man ; Gao, Yi ; Ng, Tung Him ; Yeung, Cherlie Lot Sum ; Wong, Samuel Wan Ki ; Cao, Peihua ; Ma, Angel Po Yee

AbstractThe complement system is involved in the immunosurveillance of pathogens and tumour cells. Proteomic profiling revealed that extracellular vesicles (EVs) released by metastatic hepatocellular carcinoma (HCC) cells contained a significant number of complement proteins. Complement Factor H (CFH), an abundant soluble serum protein that inhibits the alternative complement pathway, was found to be highly expressed in EVs of metastatic HCC cell lines. Here, we investigated the functional role of EV‐CFH and explored the therapeutic efficacy of targeting EV‐CFH with an anti‐CFH antibody in HCC. The results showed that EVs that are enriched in CFH promoted HCC cell growth, migration, invasiveness and enhanced liver tumour formation in mice. EV‐CFH also promoted metastasis, which was significantly abrogated when treated with an anti‐CFH antibody. These findings demonstrate an unexplored function of EV‐CFH in protecting HCC cells by evading complement attack, thereby facilitating tumorigenesis and metastasis. Lastly, we demonstrated the therapeutic efficacy of an anti‐CFH antibody in suppressing tumour formation in a syngeneic mouse model. This study suggests a new therapeutic strategy for HCC, by inhibiting EV‐CFH with a tumour specific anti‐CFH antibody.

01 Apr 2020·British Journal of HaematologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Nangaku, Masaomi ; Yasumoto, Atsushi ; Fujisawa, Madoka ; Sugawara, Yuka ; Kato, Hideki ; Yatomi, Yutaka ; Yoshida, Yoko

SummaryAtypical 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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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Preclinical	United Kingdom	Alchemab Therapeutics Ltd.Startup	07 Nov 2022

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