NEW YORK— Diagnostics startup Plexision aims to cut down delays in testing for organ transplant rejection with an antigen-based blood test for early signs a patient's immune system is attacking the donated tissue.
The University of Pittsburgh spinout said its PlexAPR assay can deliver rapid rejection-risk assessments by measuring a patient's B-cell presentation for cell surface antigens that match the human leukocyte antigen type (HLA) of the donated abdominal organ. The firm delivers results from the laboratory-developed test within about six hours of receiving a sample.
Rakesh Sindhi, CSO and cofounder of Plexision, said each PlexAPR assay uses two unique antigenic preparations, one that matches the HLA type from the organ donor and a second reference preparation that has an HLA type distinct from the patient and organ donor. The company measures and compares how often the patient's circulating B cells react with the antigens in each preparation, which can indicate whether the patient's immune system is already primed to defend against the donated organ. A ratio of 1.1:1 or higher indicates an elevated risk of rejection.
"The test is suited for surveillance of graft health at any time after transplantation but should always be used with available clinical and laboratory information to make decisions," Sindhi said. "A unique benefit of rapid results is that, if rejection is suspected based on clinical and laboratory information and this impression is confirmed quickly with this test, caregivers can act while they are coordinating a biopsy or waiting for results of a biopsy."
The firm also said last week that it has started offering another prognostic blood test, PlexCMV, for the risk of cytomegalovirus infection and transplant rejection. That assay measures the risk of cytomegalovirus infection based on T-cell immunity to the virus.
In a study involving 138 pediatric liver or intestine transplant patients, Plexision found its PlexAPR assay was predictive of acute cellular rejection in the 60 days following the test. The results, first published Oct. 21 on BioRxiv, indicate the test's performance on post-transplant samples suggested it had sensitivity, specificity, and positive and negative predictive values nearing or exceeding 80 percent.
The authors wrote that healthcare providers could use the test results to validate the need for confirmatory biopsies or develop treatment plans while waiting for biopsy results. They also found a connection between persistent markers of rejection and late graft loss, although Sindhi said he wants further validation of those results.
Sindhi said Plexision has similar specificity and sensitivity to blood tests already on the market, but its advantage is in the fast turnaround for results. He said competitors using other genomic technologies, such as cell-free DNA assays, deliver results about 48 hours after the laboratories receive samples.
"I don't think any competitor can come close to delivering this level of prediction within six hours of us receiving a sample," he said.
Plexision is competing against commercial cfDNA-based tests from CareDx, Natera, and Eurofins, each of which has multiple assays for monitoring signs of organ rejection. Eurofins also offers DNA microarray tests to rule out subclinical kidney transplant rejection, and Thermo Fisher Scientific's One Lambda also offers assays for donor-specific antibodies and antibody-mediated rejection.
More competitors are planning to enter the market, too. Verici Dx is developing tests that use gene expression-based immune system profiling to determine how aggressively a patient's immune system is likely to respond to a transplanted kidney. And Bio-Techne has been collaborating with Thermo Fisher to develop a urine-based kidney transplant rejection assay.
John Bucuvalas, professor of pediatrics at the Mount Sinai Kravis Children's Hospital, chief of the division of pediatric hepatology, and director of solid organ transplant outreach for Mount Sinai's Recanati/Miller Transplantation Institute, said Plexision's results are promising. Further study could show whether the assay results are predictive enough to aid decisions on when to conduct biopsies and when to modify immunosuppression treatments without biopsies.
"I'm not sure we're there yet, but that's where I think you would want to get to," he said.
The standard of care for deciding when to conduct biopsies in liver transplant patients involves testing for serum aminotransferase and GGT levels as biomarkers for liver injury, Bucuvalas said. But those signs of injury are not specific to rejection and can instead reflect effects of medications or infections, and he was one of the authors of a 2018 article in Gastroenterology that indicates patients with normal results on liver tests also may have subclinical changes in liver histology.
Bucuvalas, who is not connected with Plexision, said Sindhi's Pittsburgh-based group has been "pushing the envelope for years" on transplant assay development. If their assay proves to be predictive enough to reduce the need for biopsies, that could be particularly beneficial for pediatric patients, who require general anesthesia for a biopsy and often travel further than adult patients for biopsies because fewer healthcare centers cater to pediatric patients.
The ideas behind the assay began incubating in 2005 within Sindhi's laboratory at the University of Pittsburgh, where he is now the director of pediatric transplant surgery. In 2006, he started a National Institutes of Health-funded research project with a goal of identifying genetic susceptibility to transplant rejection among children with liver transplants.
Sindhi and his brother, Rajeev Sindhi, established Plexision's reference laboratory in 2012. The University of Pittsburgh has a stake in the startup, which has been self-funded by the founders and their families. The firm has sought external investments, said Sindhi.
The team's work led to a previous prognostic assay, Pleximmune, which gained a US Food and Drug Administration Humanitarian Device Exemption in 2014 for evaluating the risk of acute cellular rejection among pediatric liver or small bowel transplant patients. That test uses a similar concept as the PlexAPR but instead measures the immune response to the donor's tissue by targeting CD154 expression on memory T-cells.
Plexision processes the tests out of its CLIA- and CAP-accredited laboratory in Pittsburgh and has no intentions of taking it through the FDA clearance process, Sindhi said. Their customers today predominantly send samples from the East Coast and mostly for pediatric patients. Sindhi also noted that the firm is working with reimbursement consultants on CMS coding options.