Immune Cells and Type I Interferon in Systemic Lupus Erythematosus Patient Urine and Kidney Immunopathology Public Deposited

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  • March 19, 2019
Creator
  • Scott, Eric
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • Murine models have demonstrated that systemic lupus erythematosus (SLE) results in kidney damage due to antibody mediated tissue destruction. Studies of peripheral blood immune subsets in patients revealed the importance of T and B lymphocyte subsets that drive pathological antibody production. The immunopathological events in the kidneys of human SLE nephritis (LN) are poorly understood, in part due to a paucity of serial patient samples related to the risk of tissue biopsy procedures. To circumvent this, we investigated readily available patient urine that might contain immune mediators that correlate with kidney pathology and function. Flow cytometry analysis was performed on peripheral blood and urine cells of 28 non-LN patients and 41 LN patients. The urine immune cell phenotypes were correlated with the class of LN and kidney function. Sixty percent of non-LN patients had urine lymphocytes. Non-LN urine B cells were naïve and memory cell subsets and T cells were predominantly CD8+. In contrast, nearly all LN patients had urine lymphocytes. In half of LN patients, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4+. In addition, the urine contained plasmacytoid dendritic cells (pDCs) and IFNα/β. Patients with significantly increased PB/PCs were more likely to have proliferative nephritis, exhibit a significant loss of kidney function, and progress to end stage renal disease (ESRD). We find that urine provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD.
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  • In Copyright
Advisor
  • Wan, Yisong
  • Vilen, Barbara J.
  • Tisch, Roland
  • Sarantopoulos, Stefanie
  • Clarke, Stephen H.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2015
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  • Chapel Hill, NC
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