T cell activation in patients with ANCA-associated vasculitis: inefficient immune suppression by therapy

Background and aims: Patients with vasculitic disease and autoantibodies to neutrophil cytoplasmic antigens (ANCA) generally respond to immunosuppressive therapy with a reduction of the inflammation and lowering of the ANCA titre. However, most patients experience relapses, sometimes after years of quiescence. In the present study we addressed the question whether the relapsing nature of this disease could be dependent on an underlying T cell activation. Patients were analyzed at disease onset, in remission while on treatment, and in quiescence. Patients and methods: Blood lymphocyte subsets and the expression of molecules associated with T cell activation were analyzed by flow cytometry and soluble interleukin-2 receptor (sIL2r) levels in serum by ELISA. Three patient categories (la, Ib and 2) were studied and compared with age-matched healthy controls (la: 16 patients at onset of the disease before therapy, Ib: 10 patients from group la, re-analyzed after first remission, 2: 11 other patients in quiescence, 2 - 10 years after debut). Results: All patient groups, la, Ib and 2, showed signs of T cell activation such as reduced CD28 on CD3+ and increased of the early T cell activation marker CD69 on CD3+, as well as of CD38 on CD8+ T cells. The sIL2r levels were significantly raised in all patient categories (la: 4280, Ib: 1844, 2: 2882 ng/ml) compared with the controls (923 ng/ml). Conclusion: Patients with ANCA-positive vasculitis show an increased expression of T cell activation markers irrespective of immunosuppressive therapy or disease phase. Such memory cells may form the basis for the remitting course of vasculitides and would be a rational target for new strategies of therapy.