Novel Biomarker Could Lead to Earlier Diagnosis of TA-TMA

Published May 2019 | Pediatric Nephrology

About 35% of children and young adults receiving hematopoietic stem cell transplants (HSCT) develop transplant-associated thrombotic microangiopathy (TA-TMA). The manifestations of TA-TMA can range from mild anemia, thrombocytopenia, and acute kidney injury to severe multi-organ failure and even death.

In 2012, researchers at Cincinnati Children’s pioneered the use of eculizumab as a treatment for children with severe TA-TMA. But a lack of consistent non-invasive diagnostic criteria presented a significant roadblock to early diagnosis and effective care.

A discovery by Meredith Schuh, MD, could lead to a breakthrough. Schuh, a pediatric nephrologist at Cincinnati Children’s, recently identified a 17kDa haptoglobin degradation product as a potential early biomarker for the disease.

Schuh’s study used serum samples from patients who underwent HSCT at Cincinnati Children’s. Samples were taken as part of a routine screening protocol prior to transplant, and then weekly throughout treatment. This allowed for investigation at time points two weeks before and at clinical TMA diagnosis.

Schuh used mass spectrometry and proteomic analysis to identify a protein of interest (haptoglobin degradation product) that was upregulated two weeks prior to TMA diagnosis. She then validated the product as a potential biomarker through Western Blot to determine chronological changes in these small haptoglobin fragments before and at TMA diagnosis. A 17-kDa haptoglobin fragment differed significantly from pre-TMA to clinical TMA diagnosis.

“Next we want to develop a clinical-grade assay for a large-scale validation and quantification,” says Schuh, whose study was a collaboration with the Division of Bone Marrow Transplant and Immune Deficiency. “If that provides sufficient validation, we could potentially incorporate the 17-kDa haptoglobin degradation product as part of an early biomarker panel.”