Background/Purpose: ANCA-associated vasculitis (AAV) is a multisystem autoimmune disease that often affects the kidneys. It is unclear why some patients with AAV have kidney involvement while others do not. To investigate the mechanisms underlying these phenotypes, this study examined plasma and urine cytokine profiles in patients with active renal and non-renal AAV (AAGN and NR-AAV, respectively), and healthy controls (HC).

Methods: Levels of 200 cytokines were measured in the plasma and urine of 6 patients with active AAGN, 9 patients with NR-AAV, and 3 HC using a human cytokine array. Urine cytokine levels were corrected to urine creatinine and an analyte-to-creatinine ratio was utilized for analysis. Levels in the three groups were compared using ANOVA. Analytes with false discovery rate (FDR)-corrected p-values < 0.05 were further compared using Tukey HSD post-hoc test.

Results: Patient Characteristics are depicted in Table 1. Most cytokines measured were similar between HC and NR-AAV patients. Compared to patients with NR-AAV, patients with AAGN had higher levels of plasma and urine cytokines that are involved in involved in Th17 signaling (IL-17A, IL-17F, IL-17R, IL-23, IL-6), Th1 response (IL-12, GM-CSF, IFNg, TNFa), chemotaxis (especially for T-cells, monocytes, and dendritic cells – eotaxin-2, I-TAC, Lymphotactin, MCP-3, MIP-3a, CCL23), B and T-cell crosstalk (B7-1, CD40, CD40L), and angiogenesis (VEGFR1, FLT4, VEGF-C, VEGF-D, SDF1a) (Figure 1).

Conclusion: Compared to NR-AAV, AAGN is associated with an increase in plasma and urine levels of many pro-inflammatory cytokines. T-cell differentiation, signaling, and crosstalk seem to be the most prominent molecular processes that are active in patients with AAGN. These data suggest a prominent role of T-cells in AAGN which have the potential of being leveraged therapeutically.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/plasma-and-urine-cytokine-profiles-in-active-anca-associated-vasculitis/