Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. May 6, 2015; 4(2): 213-222
Published online May 6, 2015. doi: 10.5527/wjn.v4.i2.213
Oxidative stress as a potential causal factor for autoimmune hemolytic anemia and systemic lupus erythematosus
Junichi Fujii, Toshihiro Kurahashi, Tasuku Konno, Takujiro Homma, Yoshihito Iuchi
Junichi Fujii, Toshihiro Kurahashi, Tasuku Konno, Takujiro Homma, Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata-city, Yamagata 990-9585, Japan
Yoshihito Iuchi, Department of Biological Chemistry, Faculty of Agriculture, Yamaguchi University, Yamaguchi-shi, Yamaguchi 753-8515, Japan
Author contributions: Fujii J mainly wrote the paper; Kurahashi T, Konno T, Homma T, and Iuchi Y contributed to the original studies, which have been published or will be submitted soon, and provided ideas for this manuscript.
Supported by The Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation from the Japan Society for the Promotion of Sciences.
Conflict-of-interest: There are no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Junichi Fujii, Professor, Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, 2-2-2 Iidanishi, Yamagata 990-9585, Japan. jfujii@med.id.yamagata-u.ac.jp
Telephone: +81-23-6285227 Fax: +81-23-6285230
Received: June 16, 2014
Peer-review started: June 18, 2014
First decision: August 14, 2014
Revised: January 5, 2015
Accepted: February 4, 2015
Article in press: February 9, 2015
Published online: May 6, 2015
Abstract

The kidneys and the blood system mutually exert influence in maintaining homeostasis in the body. Because the kidneys control erythropoiesis by producing erythropoietin and 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) deficiency in C57BL/6 mice. SOD1 deficient mice exhibit 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.

Keywords: Autoimmune hemolytic anemia, Systemic lupus erythematosus, Red blood cells, New Zealand black mice, New Zealand white mice

Core tip: Superoxide dismutase (SOD1) deficient C57BL/6 mice exhibit 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 indicated that reactive oxygen species (ROS) levels in red blood cells are originally high and further elevated during aging. Transgenic overexpression of human SOD1 in erythroid cells effectively suppresses ROS elevation and ameliorates AIHA symptoms in NZB mice. 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.