New complement tests developed by the Nephrology Clinical Laboratory team at Cincinnati Children’s will provide faster turnaround times and the functional activity level of proteins in the complement cascade.

Specialized Assays

Complement proteins are part of the body’s immune system. Abnormal levels of complement protein can indicate an autoimmune disease or other health condition.

Complement blood tests that measure the amount of complement proteins in the blood use high-complexity, manual methods. To decrease turnaround time and improve accuracy, Cincinnati Children’s Nephrology Clinical Lab has developed a novel approach to measuring these proteins.

The new method converts the traditional complement blood tests to high through-put nephelometric tests, which quickly and accurately measure protein levels in the blood, Thelma Kathman, clinical lab supervisor, says.

Nephelometry measures the amount of light scattered or reflected and is the gold standard for measuring protein levels. The refined microparticle-enhanced nephelometric immunoassays developed by the Nephrology Clinical Lab provide higher sensitivity and lower reagent consumption.

“This will help our patients,” says Stefanie Benoit, MD, clinical director of the laboratory. “Better data, faster. This is what we are here for.”

Measuring Protein Function

The Nephrology Clinical Lab were pioneers in monitoring complement blockade. The first approved complement blocker, eculizumab, can only be used by the body once. The amount of drug in the blood goes down as it is used. This makes it easy to know whether the patient is getting too much or not enough drug. The Cincinnati Children’s team has been assisting doctors in the escalation and weaning of eculizumab to match the needs of their patients with their lab-developed eculizumab drug-level assay.

Novel complement-blocking medications, like ravulizumab and other up-and-coming drugs, have a recycling mechanism so the drugs can be used by the body more than once. This produces sustained inhibition of complement proteins and allows for extended, multiweek dosing. This is much more convenient for patients. But it makes it harder for doctors to know if the dose is too much or not enough.

The functional tests developed at Cincinnati Children’s will help doctors answer these questions. By looking at both the amount of protein and how active the protein is, doctors will be able to assess the effect the drug is having despite the recycling mechanism. Kathman says the C5 functional complement assay provides a way to determine if ravulizumab is doing its job.

“We want to be ahead of new treatments. We’re building testing panels to help clinicians navigate the exciting future ahead. So, they can monitor complement activity and complement blockade,” says Benoit.

Expanding Future Uses

The Nephrology Clinical Laboratory already serves more than 300 institutions across the country with its testing services. The new complement tests enhance and expand its monitoring and testing panels. Benoit says the new complement tests “will give providers faster and more complete data to monitor the complement cascade in patients being treated with complement-blocking medications, such as ravulizumab, as well as all of the exciting novel medications that are currently in phase 2 and phase 3 clinical trials.”

Whenever possible, the team attends clinical and pharmaceutical complement meetings to stay at the cutting edge of where the complement field is going. “We try to anticipate what the doctors dealing with these diseases will need,” Benoit says. “How their tools will expand and what questions will need answering.”

The complement tests can be used for diagnostic testing but are also available for research support. The Nephrology Clinical Laboratory is a certified Good Clinical Laboratory Practice lab with experience in supporting pharmaceutical studies and clinical and research trials.