aHUS’ Cause in 8 cases linked to complement activating conditions

Eight cases of atypical hemolytic uremic syndrome (aHUS) that occurred in people with underlying conditions that could have caused increased activity of the complement cascade – a part of the immune system that thought about a HUS . to drive – were described in a recent report.

“The cases described provide further evidence that a vicious cycle of complement activation may be a common pathogen.” [disease-causing] trait in many forms of HUS,” the scientists wrote.

The report, “Complement-enhancing disorders in atypical hemolytic uremic syndrome: a Canadian case series”, was published in the Canadian Journal of Kidney Health and DiseaseThe research was funded by Alexion

The complement cascade is a group of immune proteins that are normally present in the blood in an inactive state. In response to certain stimuli – for example an infection – the cascade is activated, with one complement protein activating others, such as a series of falling dominoes. This eventually triggers a powerful inflammatory response that can help fight infection.

Still, uncontrolled complement activation is thought to drive aHUS. The approved aHUS treatments Ultomiris (ravulizumab-cwvz) and Soliris (eculizumab), both of which are marketed by Alexion, now part of AstraZeneca, work by blocking complement activity.

Scientists in Canada described eight cases of people diagnosed with aHUS. In each case, individuals had an underlying condition that could predispose them to increased complement activation. These conditions include pneumonia, autoimmune diseases, complement-mediated kidney disease, pregnancy, and bacterial diarrheal disease.

“We report cases of aHUS where a complement-enhancing disorder (CAC) was suspected,” the researchers wrote.

In addition to the presence of such underlying conditions, clinical data for all eight patients were broadly indicative of disease caused by the overactivation of the complement cascade.

In several patients, laboratory tests were indicative of complement activation (ie, low blood C3 levels or C5b-9 deposition). Genetic testing also revealed that four of the eight patients had disease-causing mutations in complement-related genes.

Also note that all patients showed rapid improvement after treatment with the complement-blocking drug Soliris and/or with plasma exchange, a procedure that replaces plasma, the non-cellular part of blood, which can reduce complement activity by pro- – inflammatory signaling molecules from the bloodstream.

Overall, these findings “add to existing lines of evidence that the complement pathway may be involved in” [aHUS] and that it should be considered a therapeutic target of interest,” the researchers wrote.

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