Increasing Activity of Complement Factor H May Ease Symptoms in aHUS Patients

Increasing Activity of Complement Factor H May Ease Symptoms in aHUS Patients

New research shows how an antibody was able to enhance the function of a member of the complement system, called complement factor H (FH), responsible for keeping this system in check.

Augmenting FH with the newly discovered antibody reduced red blood cell burst in blood samples of atypical hemolytic uremic syndrome (aHUS) patients.

Most importantly, the antibody had no negative effects on the complement-mediated killing of bacteria.

The study, “Potentiation of complement regulator factor H protects human endothelial cells from complement attack in aHUS sera” was published in the journal Blood Advances.

aHUS is characterized by the progressive destruction of red blood cells due to impaired function of the complement system, a set of more than 50 blood proteins that form part of the body’s immune defenses.

Damaged red blood cells are prone to form aggregates, leading to clots that clog the kidney’s filtering system, potentially leading to kidney failure.

Complement regulators are proteins whose job is to regulate and prevent complement-mediated damage, and one of the most important of these factors is called complement factor H (FH). However, in 20% to 30% of aHUS patients, the function of FH is impaired due to loss-of-function mutations or autoantibodies reacting against it.

Treatment with Soliris (eculizumab), a complement inhibitor developed and marketed by Alexion, has proven to be successful in aHUS by blocking signals from the immune system’s complement pathway, preventing overactivation and red blood cell damage.

However, one limitation of Soliris is the fact that its use may increase the risk of bacterial infections, such as Neisseria meningitidis.

“Because FH plays a crucial role in the regulation of complement on human cells, we investigated the possibility of enhancing FH activity to improve complement regulation on human cells,” researchers said.

They generated several different antibodies against the human FH and identified one, which they called anti-FH.07, that increased FH-mediated protection of human endothelial cells (those lining the inner wall of blood vessels) from the malfunctioning complement.

Most importantly, the antibody didn’t affect the complement’s activity against bacteria.

Researchers tested the antibody in blood samples from 11 aHUS patients carrying different mutations in the FH gene. Adding anti-FH.07 decreased the disruption of red blood cells (hemolysis).

Overall, these results suggest that FH regulatory activity of the complement system can be increased. Moreover, the antibody discovered in this study augments the activity of FH without affecting complement-mediated destruction of bacteria.

“We believe that enhancing FH activity is of great interest as a safe alternative to the current therapeutic interventions in complement-mediated diseases,” the study concluded.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.
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Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.