Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody–associated vasculitis

Abstract

Numbers of circulating CD4+ effector memory T cells are proportionally increased in patients with proteinase 3 antineutrophil cytoplasmic antibody-associated vasculitis (AAV) whose disease is in remission and are decreased during active disease, which presumably reflects their migration toward sites of inflammation. Since renal infiltrating cells may appear in urine, we investigated the presence of CD4+ effector memory T cells in urinary sediment as a reflection of renal disease activity in AAV. CD4+ effector memory (CD45RO+CCR7-CD3+CD4+) T cells were quantitated in the urine and peripheral blood of patients with AAV with renal involvement (n = 33), patients with AAV without renal involvement (n = 18), patients with AAV whose disease was in remission (n = 29), and patients with active disease (n = 22), using 4-color flow cytometric analysis. Numbers and percentages of urine CD4+ effector memory T cells in 12 patients with AAV with active renal disease were obtained over several weeks of followup during remission induction. A notable increase in urine CD4+ effector memory T cell numbers was observed in patients with active renal AAV compared with patients whose disease was in remission and patients with active disease without renal involvement. The increase in these cells in the urine of patients with active renal AAV was accompanied by a reciprocal decrease in these cells in peripheral blood. Results from followup analysis showed a clear reduction in urine CD4+ effector memory T cells following treatment. Moreover, a negative correlation was observed between percentages of circulating and urine CD4+ effector memory T cells, consistent with their migration toward sites of inflammation. Our findings indicate that the presence of CD4+ effector memory T cells in urine reflects renal involvement in AAV. Flow cytometric analysis of these cells in urine may contribute to assessing renal disease activity in patients with AAV.