Research Awards Recipients

Lay Abstract

Childhood immunoglobulin A nephropathy (cIgAN) is a prevalent kidney disease in children, yet it often goes unnoticed until adulthood when limited treatment options are available, putting young patients at high risk of kidney failure. IgA Nephropathy is a rare, autoimmune disease that compromises the kidneys, especially the kidney’s primary function to filter the blood to remove waste products from the body. One of the symptoms of IgAN is red urine. Around 20-40% of people with IgAN will develop end-stage kidney disease, which means they will need dialysis or kidney transplantation to survive. IgAN onset is often during young adulthood but can appear during childhood, affecting the child's development. Our research program aims to change this by improving early diagnosis and treatment for cIgAN. We focus on a protein called sCD89, which shows promise as an early biomarker for cIgAN. This protein is part of the immune system and plays a crucial role in how the disease develops. By understanding its role, we can potentially detect cIgAN at an earlier stage and provide more effective treatments. Our research has uncovered several key aspects of cIgAN: - Biomarker Discovery: We have found elevated levels of sCD89 in young patients with IgA nephropathy, suggesting it could serve as an early warning sign for the disease. This discovery may lead to quicker and more accurate diagnoses. - Mechanisms of Disease and Inflammatory Response: Our studies have shown that sCD89 triggers an inflammatory response in the kidneys. We have identified important components in the development of cIgAN, including the TfR1 receptor and the mTOR pathway. By understanding this process, we can work on ways to intervene and prevent further damage. These components are like puzzle pieces, and understanding how they fit together can help us develop targeted therapies. - Role of APRIL: We have also discovered that sCD89 stimulates the production of a proinflammatory molecule called APRIL. Although we are still investigating its exact role, we suspect that APRIL plays a vital role in the interaction between different cells in the kidney. Our research program is structured around three main goals: Aim 1: Identifying Specific Markers. We aim to define the various forms of sCD89 and APRIL found within the IgA nephropathy deposits using a sophisticated technique called mass spectrometry. This will help us pinpoint the exact forms that are associated with the disease. Aim 2: Understanding the Disease Process. We are working on unraveling how sCD89 triggers inflammation in the kidneys and activates certain pathways. By exploring the molecular and genetic aspects of the disease, we hope to identify new ways to target it. Aim 3: Exploring Cell Interactions. We will be using a unique model called GlomSpheres to investigate how sCD89 and APRIL affect the communication between different cells in the kidneys. This model allows us to simulate and study these interactions more closely. Our research brings together clinical and basic scientific approaches, utilizing resources and data from biobanks in France and Canada. We are dedicated to understanding the role of sCD89 in the development of cIgAN, how it influences communication between different cells in the kidney, and ultimately, how we can develop non-invasive tests to monitor kidney inflammation. This could lead to fewer kidney biopsies and better management of kidney disease. In essence, our work holds the potential to significantly benefit young cIgAN patients by offering earlier diagnoses and more effective treatments. It is an important step toward improving the quality of life for those affected by this kidney disease.