The role of interleukin-17 in the associations between systemic lupus erythematosus and ANCA-associated vasculitis

Abstract

We read with great interest the recent contribution by Hervier et al. [1]. They reported four cases of de novo systemic lupus erythematosus (SLE) associated with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) and described the clinical significance of this association [1]. However, they did not explicate the precise pathomechanism between the two diseases. We would like to suggest a possible pathogenesis of the association of SLE with AAV. Recently, there have been some reports showing that interleukin (IL)-17 may play an important role in the pathogenesis of both SLE and AAV [2–5]. The activation of IL-17/IL-23 axis has close relationship in a lot of inflammatory autoimmune diseases [2]. In the study of Wong et al. [2] plasma IL-17 and IL-23 concentrations and the number of Th17 cells were significantly elevated in SLE patients than control subjects and elevated IL-17 concentrations correlated positively and significantly with SLE disease activity index (SLEDAI). Furthermore, Zhang et al. [3] reported that IL-23-treated lymph node cells from lupus-prone mice may transfer disease to Rag1-deficient mice and CD3(?)CD4(-)CD8(-) double-negative T cells from lupus-prone mice express high amounts of IL-17. Also, as disease progressively worsens, the expression of IL-17 and of IL-23 receptor in lymphocytes from these mice increased. Conversely, Kyttaris et al. [4] showed IL-23R-deficient lupus-prone mice display decreased numbers of that double-negative cells and IL17A-producing cells in the lymph nodes and produce less anti-nuclear antibody (ANA). Recently, Gan et al. [5] reported that wild-type mice developed necrotizing glomerulonephritis (GN) with an influx of glomerular leukocytes and albuminuria but mice deficient in the key Th17 effector cytokine IL-17A were nearly completely protected. Nogueira et al. [6] found that serum IL-17A and IL-23 levels were significantly elevated in acute AAV patients compared to healthy controls, but importantly, remained elevated in a proportion of convalescent patients. Patients with elevated levels of IL-23 compared to those with low IL-23 had more active disease as measured by Birmingham Vasculitis Activity Score and had higher ANCA titers. These data implicate the Th17 axis and specifically IL-23 as mediators of more severe disease in AAV. Therefore, there is a possibility that IL-17/IL-23 axis might have central role in the pathogenesis of SLE and AAV. However, further studies are necessary to elucidate the molecular role and signaling transduction pathway of IL-23 and IL-17 and serial changes of IL-17 after rituximab treatment in AAV.