Transfusion Medicine
The focus of my lab’s research is on detection and characterization of platelet and neutrophil-reactive antibodies and antigens and studies of the glycoproteins that carry these antigens. The primary goal is to apply the results of this work to develop new and improved clinical tests for use by the Diagnostic Laboratories at Blood Center of Wisconsin.
Drug-Dependent Platelet Antibodies
Some people develop antibodies against their platelets, red blood cells, or white blood cells following receipt of medications. Our Platelet & Neutrophil Immunology Reference Lab currently tests for drug-dependent platelet and white blood cell antibodies, and to date, we have identified drug-dependent antibodies in patients’ blood samples for over 60 drugs, including vancomycin, sulfa-drugs, beta-lactam antibiotics, and even over-the-counter medications like ibuprofen and Tylenol (view complete list). We currently have laboratory and clinical studies in progress, together with researchers at BRI, to better understand the formation of drug-dependent antibodies and their clinical significance.
Studies of CD36 on Platelets
We showed that ~3% of African-Americans lack the protein CD36/glycoprotein IV on their platelets. CD36 is a receptor for malaria-infected red blood cells, and absence of the protein from platelets and monocytes may play a role in malaria infection. Studies are ongoing to identify the rate of alloimmunization to CD36 in patients with CD36 deficiency and the role of these antibodies in immune platelet disorders.
Low Frequency Human Platelet Alloantigens (HPA)
The Platelet & Neutrophil Immunology Lab performs testing on over 400 samples each year to aid physicians in the clinical diagnosis of fetal & neonatal alloimmune thrombocytopenia (FNAIT). FNAIT is a disorder in pregnancy in which a mother makes antibodies against her baby’s platelets resulting in destruction of the baby’s platelets leading to severe bleeding into the baby’s brain (ICH) and even death. It is thus important that laboratory testing for FNAIT be thorough, including the ability to detect maternal antibodies reactive with low frequency or new HPA (view list Platelet Antigen Database). We are working with cutting-edge methods to detect and characterize newly discovered HPA.
Leukocyte Antibodies in TRALI
Transfusion-Related Acute Lung Injury (TRALI) is a severe reaction that some patients experience following transfusion of blood or plasma. TRALI is currently the number one cause of transfusion-related death reported to the Food and Drug Administration (FDA). In a significant number of TRALI cases, the plasma from donors of the implicated blood products contains leukocyte antibodies (HLA and neutrophil) that cause activation of the patient’s neutrophils, leading to TRALI. One of the antigens targeted by such antibodies is designated human neutrophil antigen (HNA)-3a, which has been implicated in numerous severe cases of TRALI, many of them fatal. We identified the protein carrier (CTL2) of HNA-3a and HNA-3b, alleles of gene SLC44A2. We are also investigating the use of tests that could be used to screen blood donors for antibodies against HNA-3 as a TRALI risk-reduction measure.