Floege J, Burg M, Al Masri A N, Gröne H J, von Wussow P
Division of Nephrology, Medical School, Hannover, Germany.
Am J Kidney Dis. 1999 Mar;33(3):434-40. doi: 10.1016/s0272-6386(99)70179-4.
Both viral infections and dysregulated cytokine synthesis have been implicated in the pathogenesis of immunoglobulin A nephropathy (IgAN) and Henoch-Schönlein purpura (HSP). Mx 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 (approximately 3 days) markedly exceeds that of IFN-alpha/-beta (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 (<2 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-alpha2 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-alpha2) 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.
病毒感染和细胞因子合成失调均与免疫球蛋白A肾病（IgAN）和过敏性紫癜（HSP）的发病机制有关。Mx蛋白由I型干扰素（IFN-α、-β、-ω）特异性诱导产生，并且在检测例如病毒诱导的体内IFN-α/-β产生方面非常敏感，因为Mx的生物半衰期（约3天）明显超过IFN-α/-β的生物半衰期（20至90分钟）。采用酶联免疫吸附测定（ELISA）法检测了35例IgAN患者和5例HSP患者的79份血样中白细胞的Mx浓度。检查时所有患者均无感染症状。与正常白细胞Mx浓度（<2 mU/1000个白细胞）相比，79份IgAN/HSP患者样本中只有3份显示Mx浓度轻度升高（范围为2.2至3 mU/1000个白细胞）。相比之下，内源性IFN产生增加的患者（红斑狼疮）或接受IFN-α2治疗的患者白细胞Mx浓度高达35 mU/1000个白细胞。在IgAN和HSP患者中，白细胞Mx浓度与各种临床参数无关。免疫组织化学检查显示，在IgAN不同阶段患者的8份肾活检标本中未检测到肾Mx表达，而对照标本（接受IFN-α2治疗患者的皮肤）显示细胞Mx表达丰富。此外，体外培养的人系膜细胞在暴露于IFN-α或IFN-β后显示出明显的Mx产生。我们得出结论，在IgAN/HSP患者中，未检测到I型干扰素系统激活或失调的证据。
