Antibody Biomarkers of Cryptococcosis in Immunosuppressed Solid Organ Transplant Recipients

Project Abstract Dr. Hyun Ah Yoon proposes a mentored clinical and translational research project and career development plan to identify antibody (Ab) biomarkers of risk for cryptococcosis in organ transplant recipients being started on immunosuppression. Her study will test the hypothesis that immunosuppression induces changes in plasma immunoglobulin (Ig) levels and cryptococcal capsular polysaccharide glucuronoxylomannan (GXM)-binding, and/or naturally occurring laminarin-binding Ab levels, and that these changes correlate with the risk of cryptococcal disease in relation to the presence of absence of Ab functionality. Her published data support the hypothesis and aims demonstrating that compared to controls, relative differences in plasma Igs, GXM- and naturally occurring laminarin-binding Ab levels were associated with cryptococcosis. To test her hypothesis, In Aim 1, Dr. Yoon will retrospectively identify kidney transplant candidates from an ongoing longitudinal prospective study at Montefiore Medical Center (MMC) who are about to start immunosuppression and do not have cryptococcosis. She will then determine Ab levels over 3 years as a function of immunosuppressive drug type, dosage, blood level and duration. In Aim 2, she will analyze the plasma Ab function of organ transplant recipients diagnosed with cryptococcosis at MMC and University of Alabama at Birmingham to identify Ab correlates of protection against disease or progression over a year. Her study will generate new knowledge on the effect of immunosuppression on Ab markers and how Ab functional attributes correlate with cryptococcosis risk and/or disease outcome in high-risk organ transplant recipients. The long-term goal is to identify HIV- negative patients at risk for cryptococcosis or poor clinical outcome earlier, intervene, and reduce morbidity and mortality by testing the proposed Ab biomarkers in a multi-center prospective clinical trial. The proposed training plan includes a combination of didactic training and mentored clinical and translational investigation that will allow Dr. Yoon to build on the preliminary data and essential laboratory and analytic skills she started to develop during her master’s degree in clinical research methods at Einstein, which she completed with distinction in May 2022. Her career development plan proposes mentored training in 1) laboratory techniques in Ab immunology, 2) longitudinal study design and analysis of comprehensive clinical and translational data, 3) leveraging her data to develop an independent grant proposal to conduct a clinical trial applying the biomarkers. Additional training will be accomplished by enrolling in advanced didactic courses and presenting at national and international conferences. Dr. Yoon will be mentored and guided by renowned mentors and collaborators with extensive experience in cryptococcal pathogenesis, Ab research, fungal immunology, clinical and translational research, and epidemiology/biostatistics, which will allow her to develop her own distinct research trajectory. Upon completing this project, Dr. Yoon will have acquired substantial breadth and depth of clinical and translational research training and be well-positioned to begin an independent research career and pursue extramural funding.