Versiti Blood Research Institute (VBRI) research scientist Nanyan Zhang, MD, PhD, was recently published in the prestigious medical journal Blood for her work exploring a phenomenon called fetal/neonatal alloimmune thrombocytopenia (FNAIT). FNAIT occurs when an expectant mother and her unborn baby have mismatched platelet surface antigens. The mother’s body develops an antibody to the baby’s platelets and begins attacking and destroying them, leading to excessive bleeding.

Key to effectively diagnosing FNAIT is detecting the mother’s antibodies against human platelet antigens (HPAs) that are expressed on the baby’s platelets. Researchers at VBRI have conducted extensive work to identify HPAs that can cause FNAIT and to develop diagnostic assays to improve patient care. However, existing diagnostic testing for FNAIT leaves room for improvement. “We are involved in this work,” Dr. Zhang said. “We are trying to develop a better assay to identify the alloantibody that causes FNAIT.”

Of the more than 30 known HPAs, HPA-9b is a rare antigen that often causes severe bleeding in affected babies. Detection of the anti-HPA-9b alloantibody is extremely difficult in some cases, for unknown reasons. Using cutting-edge CRISPR-Cas9 gene editing technology, combined with the induced pluripotent stem cell (iPSC) technique, Dr. Zhang found that when cells are manipulated to preserve the HPA-9b antigen on their surfaces, it is easier to detect the patient’s anti-HPA-9b antibody than it is through current, traditional testing.

In her newest research, Dr. Zhang did additional cell editing to modify the glycans, or sugars, on the surfaces of cells, which are located very close to the HPA-9b antigen. Dr. Zhang found that by modifying cells to remove the entire chain of glycans, anti-HPA-9b binding decreased, suggesting that the local glycans help to stabilize the antigen structure. Interestingly, genetic modification to remove only the terminal, negatively charged sialic acid from the glycans enhanced anti-HPA-9b antibody binding. This information not only helps to improve current knowledge of etiology of platelet alloimmune disorders, but also gives researchers a better tool to detect anti-HPA-9b alloantibodies.

“We think this will significantly help with the clinical diagnosis of FNAIT and improve patient care,” Dr. Zhang said.

About the expert: Nanyan Zhang, MD, PhD, is a research scientist in the laboratory of Peter Newman, PhD, at Versiti Blood Research Institute.