Expression of Interferon-Inducible Mx-Proteins in Patients With IgA Nephropathy or Henoch-Scho¨ nlein Purpura Ju¨ rgen Floege, MD, Michael Burg, MD, Abdul N. Al Masri, PhD, Hermann Joseph Gro¨ ne, MD, and Peter von Wussow, MD ● Both viral infections and dysregulated cytokine synthesis have been implicated in the pathogenesis of immuno- globulin A nephropathy (IgAN) and Henoch-Scho¨ nlein purpura (HSP). Mx proteins are specifically induced by type I interferons (IFN-,-β,-) and are very sensitive in detecting, for example, virus-induced, in vivo production of IFN-/-β, because the biological half-life of Mx (3 days) markedly exceeds that of IFN-/-β (20 to 90 minutes). Mx 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 Mx concentrations (F2 mU/1,000 leukocytes), only 3 of 79 samples of IgAN/HSP patients showed mildly elevated Mx 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- 2 showed leukocyte Mx concentrations of up to 35 mU/1,000 leukocytes. In patients with IgAN and HSP, leukocyte Mx concentrations were not correlated with various clinical parameters. Immunohistochemically, no renal Mx 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- 2 ) showed abundant cellular Mx expression. Furthermore, human mesangial cells in vitro showed marked Mx production after exposure to IFN- or IFN-β. We conclude that, in patients with IgAN/HSP, no evidence of an activation or dysregulation of the type I interferon system can be detected.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: IgA nephropathy; interferon; mesangial cell; virus; infection; glomerulus; MxA-proteins; Henoch- Scho¨ nlein purpura. I MMUNOGLOBULIN A nephropathy (IgAN), presenting as isolated glomerular disease (pri- mary IgAN) or as a part of Henoch-Scho¨nlein purpura (HSP), is the most common type of glomerulonephritis worldwide. 1,2 A variety of studies have implicated dysregulated cytokine expression both within the circulation and within renal tissue in the pathogenesis of IgAN. 3-9 Of the many cytokines that have been studied, the potential role of the interferon system is particu- larly interesting given that: 1. Disease exacerbations frequently occur dur- ing viral illnesses. 1 Virus infections po- tently induce type I interferon (IFN) produc- tion (IFN-,-β,-) and also, through antigenemia and T-cell activation, type II IFN production (IFN-). 10 2. Some experimental models of IgAN can be induced by viral infections. 11,12 Although uncommon, IgAN is associated with human immunodeficiency virus (HIV) in- fection. 13,14 Others have reported a high prevalence of non-HIV, non–human T- lymphotropic virus-I infection in patients with IgAN. 15 Antigens or DNA of cyto- megalovirus, hepatitis B virus, Epstein- Barr virus, and herpes simplex virus have been detected by some investigators in re- nal tissue of IgAN patients. 16-18 3. Type II IFN levels were found to be ele- vated in patients with IgAN, and peripheral blood mononuclear cells of such patients produced more type II IFN than those of control subjects. 4,5,8,9 4. Administration of both type I and type II IFN can lead to an aggravation of immune renal disease, including IgAN, mesangio- proliferative glomerulonephritis, and lupus nephritis. 19-21 In the current study, we have focused on type I IFNs, which, unlike type II IFN, are produced by many cells throughout the body in response to viral infections and during autoimmune dis- eases. 22-24 Rather than measuring serum levels or assessing tissue expression of the type I IFNs, we have investigated the leukocyte content or From the Divisions of Nephrology and Rheumatology, Medical School, Hannover, Germany; the Department of Pathology, University of Marburg, Germany; and the Sophien-Hospital, Hannover, Germany. Received July 2, 1998; accepted in revised form Septem- ber 25, 1998. Supported by grants from the Deutsche Forschungsgemein- schaft (SFB 244/C12 and a Heisenberg stipend to J.F.). Address reprint requests to Ju¨rgen Floege, MD, Division of Nephrology 6840, Medizinische Hochschule, 30623 Han- nover, Germany. E-mail: floege.juergen@mh-hannover.de  1999 by the National Kidney Foundation, Inc. 0272-6386/99/3303-0002$3.00/0 434 American Journal of Kidney Diseases, Vol 33, No 3 (March), 1999: pp 434-440