2026 Fellow Awardee

Awardee: Conor Gruber, MD, PhD, Clinical Fellow, Division of Rheumatology, Children's Hospital of Philadelphia

Study Title: Mapping Inflammatory immune profiles in Turner Syndrome for biomarker discovery

Study Summary: Individuals with Turner syndrome (45,X) have one of the highest rates of autoimmune disease among all genetic conditions, with an estimated 30–50% developing disorders such as autoimmune thyroid disease, celiac disease, type 1 diabetes, inflammatory bowel disease, or rheumatologic conditions during their lifetime. Despite this significant health burden, clinicians have limited ability to predict which individuals are most likely to develop autoimmune disease, and there are currently no therapies designed to prevent or modify the underlying immune dysfunction. This study seeks to better understand how the immune system is altered in Turner syndrome and to identify biological markers that may help predict autoimmune disease risk before symptoms develop.

By defining the cellular and molecular immune signatures associated with autoimmunity in Turner syndrome, this research aims to establish a foundation for earlier identification of individuals at greatest risk and to support the development of personalized strategies for disease prevention and treatment. The biomarkers identified through this work may ultimately guide future clinical trials of targeted immune therapies and improve long-term health outcomes for individuals with Turner syndrome. In addition, because an increased risk of autoimmune disease is shared across many sex chromosome aneuploidies, the insights gained from this study may help advance our understanding of immune dysfunction in related conditions and contribute to broader efforts to develop precision medicine approaches for autoimmune disease.

Study Design: Researchers will analyze nasal swab samples from ~30 individuals with a confirmed karyotype of 45,X; 46,XX; or 47,XXX, including participants with and without a history of autoimmune disease, and compare them with samples from healthy individuals. Using advanced immune profiling technologies, including high-dimensional mass cytometry and targeted proteomic analysis, the study will examine dozens of immune cell populations and inflammatory proteins (cytokines) that regulate immune responses. These approaches provide an unprecedented level of detail, allowing researchers to identify patterns of immune cell function and inflammatory signaling that may distinguish individuals who develop autoimmune disease from those who remain unaffected. The findings will also be compared with an independent biorepository of Turner syndrome samples to validate the most promising biomarkers.