Session Title: ACR Late-Breaking Abstract Poster Session
Session Type: Late-Breaking Abstracts
Title: Kidney resident B Cells and plasmacytoid dendritic cells (pDCs) in the urine of systemic lupus erythematosus (SLE) patients.
Renal involvement remains the principal cause of morbidity and mortality in SLE. B cells play a prominent role in kidney pathology in mouse models of SLE. In addition to producing autoantibodies, B cells produce cytokines and can present antigen to autoreactive T cells. Recently, we identified a B cell population with high expression of CD19 and CD20 and low expression of CD21 that is expanded in some human SLE patients. These high CD19 expressing cells (CD19hi) are present in ~30% of SLE patients, where they can comprise as much as 50% of peripheral blood B cells. The presence of an expanded CD19hi B cell population correlates with poor long-term outcomes of end stage renal disease and neurological complications. High expression of CXCR3 by CD19hi B cells, suggests that they are trafficking to sites of inflammation, such as the kidney.
To test this possibility we examined concurrent patient urine and plasma samples for the presence of B cells by flow cytometry. An Interferon alpha (IFNα) assay was used to determine whether levels were elevated in blood and urine. We also determined the frequency of pDCs in blood and urine by flow cytometry.
Fig. 1: B and T cells presence in SLE urine
We identified B cells in ~1/3 of patient samples that are likely of kidney origin. Patients fell into two non-overlapping groups based on B cell phenotype. In the first group, urine B cells exhibited a B cell phenotype, among which were CD19hi B cells, present at the frequency equal to the peripheral blood. In the second group, the B cells exhibited a plasmablast phenotype and these cells spontaneously secreted IgG. In addition, we found that, IFNα and pDCs, the major producers of IFNα were present in patient urine, but only in patients who had B cells in their urine. In patients depleted of B cells, B cells were still present in the urine suggesting that they are of kidney, not peripheral blood, origin Moreover, IFNα levels in plasma correlate significantly with the frequency of CD19hi B cells.
Kidney resident B cells are present in urine samples, providing access to these cells for phenotypic and functional characterization. Their presence in urine is strongly correlated with the presence of IFNα and pDCs. In addition, the presence of IFNα in peripheral blood correlates with the presence of urine B cells. These data suggest that kidney resident B cells, possibly CD19hi B cells, promote the production of IFNα by pDCs.
M. A. Dooley,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/kidney-resident-b-cells-and-plasmacytoid-dendritic-cells-in-urine-of-systemic-lupus-erythematosus-patients/