Expression of interferon-inducible Mx-proteins in patients with IgA nephropathy or Henoch-Schonlein purpura

Both viral infections and dysregulated cytokine synthesis have been implicated in the pathogenesis of immunoglobulin A nephropathy (IgAN) and Henoch-Schonlein purpura (HSP), Mr proteins are specifically induced by type I interferons (IFN-alpha, -beta, -omega) and are very sensitive in detecting, for example, virus-induced, in vivo production of IFN-alpha/-beta, because the biological half-life of Mx (similar to 3 days) markedly exceeds that of IFN-alpha/-beta (20 to 90 minutes), Mr concentrations in leukocytes were measured by enzyme-linked immunosorbent assay (ELISA) in 79 blood samples of 35 patients with IgAN and five with HSP. No patient showed symptoms of infections at the time of the examination. Compared with normal leukocyte Mr concentrations (<2 mU/1,000 leukocytes), only 3 of 79 samples of IgAN/HSP patients showed mildly elevated Mr concentrations (range, 2.2 to 3 mU/1,000 leukocytes), By contrast, patients with increased endogenous IFN production (lupus erythematosus) or patients treated with IFN-alpha(2) showed leukocyte Mr concentrations of up to 35 mU/1,000 leukocytes, In patients with IgAN and HSP, leukocyte Mr concentrations were not correlated with various clinical parameters. Immunohistochemically, no renal Mr expression could be detected in eight renal biopsy specimens of patients with various stages of IgAN, whereas control specimens (skin of patients treated with IFN-(alpha 2)) showed abundant cellular Mx expression, Furthermore, human mesangial cells in vitro showed marked Mx production after exposure to IFN-alpha or IFN-beta. We conclude that, in patients with IgAN/HSP, no evidence of an activation or dysregulation of the type I interferon system can be detected, (C) 1999 by the National Kidney Foundation, Inc.