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Mann, Simranpreet Kaur

University of British Columbia

Chronic primary systemic vasculitis (PSV) describes a group of rare and potentially life-threatening disorders characterized by the inflammation and necrosis of blood vessels in one or more vital organs. In children, PSV typically affects small blood vessels, with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) being the most common form. Compared to adult-onset AAV, AAV in children is more likely to be severe at outset and present with multi-organ involvement. Furthermore, more than 80% of children exhibit kidney involvement at initial presentation, and approximately one-third develop permanent kidney damage within the first year. Due to the rarity of childhood-onset AAV, most knowledge of the disease is obtained by studying adult-onset AAV. In adults with AAV, certain autoantibodies and urine proteins have been identified as biomarkers of risk for severe disease, kidney involvement, and relapse, and are now used to guide treatment decisions. The intent of this thesis is to assess the utility of these adult-derived tools in childhood-onset vasculitis. Using the single largest repository of retrospective data and biosamples from children with vasculitis stored at the University of British Columbia and the BC Children’s Hospital Research Institute, this thesis reports, as primary findings, a higher likelihood of presenting with kidney involvement for children who are seropositive for ANCA directed towards myeloperoxidase (MPO) compared to those with ANCA towards proteinase-3 (PR3) and those without ANCA against either autoantigen, while neither ANCA seropositivity nor specificity were informative of the risk of relapse. Additionally, none of the three urine proteins (usCD163, usCD25, uMCP-1) identified as markers of kidney disease activity in adult-onset AAV exhibited a similar utility in the pediatric population. The findings from this thesis research identify potential differences in the utility of adult-derived biomarkers between childhood- and adult-onset AAV, and, in doing so, emphasize the importance of validating these tools in children prior to their use in clinical care for this population. Furthermore, these findings highlight a need to identify novel, pediatric-specific biomarkers for the detection and monitoring of overall and kidney-specific disease in children with AAV.

Text

2024-07-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/88664

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/