Session Type: Abstract Submissions
Session Time: 5:15PM-5:45PM
Methods: Urinary cells were isolated from patients with systemic lupus erythematosus (SLE). Immunofluorescence was performed to quantify and characterize cells expressing Kv1.3. Peripheral blood T lymphocyte subsets were assayed ex vivo for Kv1.3 expression by flow cytometry. The effect of dalazatide on phorbol myristate acetate (PMA)/ionomycin-induced inflammatory cytokine expression by TEMcells was evaluated by intracellular cytokine staining.
Results: In the urine, cells expressing Kv1.3 were found in every subject studied. Kv1.3 expression was detected on CD3+ lymphocytes in 13 of 13 samples studied (mean of 52%,range 10-100%). In 4 of 6 samples, Kv1.3 was detected on CD20+ B lymphocytes (mean 35%, range 0-100%), and CD14+ monocytes/macrophages (mean 50%, range 0-100%).
In the blood, Kv1.3 expression by CD8+ TEM cells was significantly higher in patients with active lupus nephritis when compared to patients with inactive SLE or healthy controls. Dalazatide inhibited IFN-g, IL-17 and TNF-a production by both CD4+ and CD8+ TEM cells from SLE patients in a dose-dependent manner. Higher levels of dalazatide-mediated inhibition were observed in IFN-g and TNF-a-expressing CD4+ TEMcells from patients with active SLE when compared to samples from SLE patients with inactive disease.
Conclusion: Kv1.3 is detectable on urinary B lymphocytes, T lymphocytes, and macrophage, implying that inflammatory cells in the kidney may be targeted by this channel. Peripheral blood cell expression and functional data suggest that SLE T cells are more susceptible to inhibition by dalazatide than healthy T cells.
To cite this abstract in AMA style:Stevens A, Hinkle A, Yuasa M, Peckham D, Olsen C, Philips C, Iadonato SP, Probst P. Kv1.3 Expression on Urinary Leukocytes in Lupus Nephritis: Potential for Targeted Immunotherapy [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 4). https://acrabstracts.org/abstract/kv1-3-expression-on-urinary-leukocytes-in-lupus-nephritis-potential-for-targeted-immunotherapy/. Accessed September 30, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/kv1-3-expression-on-urinary-leukocytes-in-lupus-nephritis-potential-for-targeted-immunotherapy/