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Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and systemic lupus erythematosus

World Journal of Nephrology 2015年第2期4卷 213-222页

作者： Junichi Fujii Toshihiro Kurahashi Tasuku Konno Takujiro Homma Yoshihito Iuchi Department of Biochemistry and Molecular Biology Graduate School of Medical ScienceYamagata University Department of Biological Chemistry Faculty of AgricultureYamaguchi University

The kidneys and the blood system mutually exert infuence in maintaining homeostasis in the body. Because the kidneys control erythropoiesis by producing erythropoietinand by supporting hematopoiesis, anemia is associated with kidney diseases. Anemia is the most prevalent genetic disorder, and it is caused by a deficiency of glucose 6-phosphate dehydrogenase （G6PD）, for which sulfhydryl oxidation due to an insufficient supply of NADPH is a likely direct cause. Elevated reactive oxygen species （ROS） result in the sulfhydryl oxidation and hence are another potential cause for anemia. ROS are elevated in red blood cells （RBCs） under superoxide dismutase （SOD1） defciency in C57BL/6 mice. SOD1 defcient miceexhibit characteristics similar to autoimmune hemolytic anemia （AIHA） and systemic lupus erythematosus （SLE） at the gerontic stage. An examination of AIHA-prone new zealand black （NZB） mice, which have normal SOD1 and G6PD genes, indicated that ROS levels in RBCs are originally high and further elevated during aging. Transgenic overexpression of human SOD1 in erythroid cells effectively suppresses ROS elevation and ameliorates AIHA symptoms such as elevated anti-RBC antibodies and premature death in NZB mice. These results support the hypothesis that names oxidative stress as a risk factor for AIHA and other autoimmune diseases such as SLE. Herein we discuss the association between oxidative stress and SLE pathogenesis based mainly on the genetic and phenotypic characteristics of NZB and new zealand white mice and provide insight into the mechanism of SLE pathogenesis.

关键词： Autoimmune hemolytic anemia Systemic lupus erythematosus Red blood cells new zealand black mice new zealand white mice

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