To the Editor:
We read with interest the article by Mulpuru, et al1. They described a 50-year-old woman who developed Goodpasture’s disease one month after the diagnosis of Wegener’s granulomatosis1. As one of the possible mechanisms, they described that antineutrophil cytoplasmic antibody (ANCA) might initiate renal damage, which exposes the glomerular basement membrane (GBM) as an antigenic source, allowing the development of anti-GBM disease1,2. Although not extensively studied to date, there have been some reports that Th17 cell-associated cytokines might be involved in anti-GBM disease or Wegener’s granulomatosis3,4. Nogueira, et al recently reported that a subset of CD4-positive T cells characterized by inter-leukin 17 (IL-17) production (Th17 cells) might be implicated in the pathogenesis of ANCA-associated vasculitis (AAV) including Wegener’s granulomatosis3. In their study, levels of serum IL-17A and IL-23 (critically required for maintenance of the IL-17-secreting phenotype5) were significantly elevated in patients with acute AAV compared to healthy controls, and high IL-23 levels correlated with higher levels of clinical disease activity and with higher ANCA titers3.
It was demonstrated that IL-23 might be closely associated with autoreactivity to the Goodpasture antigen [noncollagenous domain of alpha-3 type IV collagen, alpha3(IV)NC1] in a form of experimental glomerulonephritis4. In that study, wild-type mice developed autoreactivity to alpha3(IV)NC1, such as humoral and cellular responses, renal histologic abnormalities, leukocyte accumulation, autoantibody deposition, and IL-17A mRNA expression (a cytokine produced by the IL-23-maintained Th17 subset)4. However, IL-23–deficient strains exhibited lower autoantibody titers, reduced cellular reactivity, diminished cytokine production [interferon-γ (Th1), IL-17A (Th17), and tumor necrosis factor-α], and less renal disease and glomerular IgG deposition4.
There is a possibility that Th17 cell-associated cytokines, especially IL-23, might be involved in the common pathogenesis of both Goodpasture syndrome and Wegener’s granulomatosis. Further studies should be performed to elucidate whether IL-23 might be related to the development of 2 diseases at the same time.
