Akinori Hara1, Kengo Furuichi1, Junya Yamahana1, Haruka Yasuda1, Yasunori Iwata1, Norihiko Sakai1, Miho Shimizu1, Shuichi Kaneko1, Takashi Wada2. 1. From the Division of Nephrology, Kanazawa University Hospital; Department of Disease Control and Homeostasis, and Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.A. Hara, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; K. Furuichi, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; J. Yamahana, MD, PhD, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; H. Yasuda, MS, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; Y. Iwata, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; N. Sakai, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; M. Shimizu, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; S. Kaneko, MD, PhD, Department of Disease Control and Homeostasis, Kanazawa University; T. Wada, MD, PhD, Department of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University. 2. From the Division of Nephrology, Kanazawa University Hospital; Department of Disease Control and Homeostasis, and Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University, Kanazawa, Japan.A. Hara, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; K. Furuichi, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; J. Yamahana, MD, PhD, Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; H. Yasuda, MS, Department of Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; Y. Iwata, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; N. Sakai, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; M. Shimizu, MD, PhD, Division of Nephrology, Kanazawa University Hospital, and Department of Disease Control and Homeostasis, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University; S. Kaneko, MD, PhD, Department of Disease Control and Homeostasis, Kanazawa University; T. Wada, MD, PhD, Department of Nephrology and Laboratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Medicine, Kanazawa University. twada@m-kanazawa.jp.
Abstract
OBJECTIVE: We examined the clinical significance of autoantibodies to the erythropoietin receptor (EPOR) in patients with systemic lupus erythematosus (SLE) who had biopsy-proven lupus nephritis (LN). METHODS: Forty-six Japanese patients with SLE with LN who had undergone renal biopsy during 1993-2014 were enrolled in this study and followed for a mean of 83 months. Sera from those patients were screened for anti-EPOR antibodies using ELISA. RESULTS: Anti-EPOR antibodies were detected in 18 (39%) of the 46 patients with SLE with anemia. Anti-EPOR antibodies were associated with low hemoglobin concentrations and reticulocytopenia. In addition, anti-EPOR antibodies were positively correlated with SLE disease activity, even though serum levels of the complement factors 3 and 4 did not differ between the 2 groups. In patients with International Society of Nephrology/Renal Pathology Society 2003 class IV LN, anti-EPOR antibodies were associated with active lesions including cellular crescents in glomeruli. Decrease in renal function was more frequently observed in patients without complete or partial renal response than in patients with it, and serum levels of the antibodies as well as renal response to treatment were significant risk factors for progression of renal dysfunction. CONCLUSION: The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.
OBJECTIVE: We examined the clinical significance of autoantibodies to the erythropoietin receptor (EPOR) in patients with systemic lupus erythematosus (SLE) who had biopsy-proven lupus nephritis (LN). METHODS: Forty-six Japanese patients with SLE with LN who had undergone renal biopsy during 1993-2014 were enrolled in this study and followed for a mean of 83 months. Sera from those patients were screened for anti-EPOR antibodies using ELISA. RESULTS: Anti-EPOR antibodies were detected in 18 (39%) of the 46 patients with SLE with anemia. Anti-EPOR antibodies were associated with low hemoglobin concentrations and reticulocytopenia. In addition, anti-EPOR antibodies were positively correlated with SLE disease activity, even though serum levels of the complement factors 3 and 4 did not differ between the 2 groups. In patients with International Society of Nephrology/Renal Pathology Society 2003 class IV LN, anti-EPOR antibodies were associated with active lesions including cellular crescents in glomeruli. Decrease in renal function was more frequently observed in patients without complete or partial renal response than in patients with it, and serum levels of the antibodies as well as renal response to treatment were significant risk factors for progression of renal dysfunction. CONCLUSION: The present study suggests that anti-EPOR antibodies might be involved in overall disease activity and active renal lesions, as well as in the impaired erythropoiesis in patients with SLE with LN. Further, the levels of anti-EPOR antibodies may be an additional predictor for renal injury.
Authors: Chiara Donadei; Andrea Angeletti; Chiara Cantarelli; Vivette D D'Agati; Gaetano La Manna; Enrico Fiaccadori; Julian K Horwitz; Huabao Xiong; Chiara Guglielmo; Susan Hartzell; Joren C Madsen; Umberto Maggiore; Peter S Heeger; Paolo Cravedi Journal: JCI Insight Date: 2019-04-23
Authors: Megumi Oshima; Akinori Hara; Tadashi Toyama; Min Jun; Carol Pollock; Meg Jardine; Stephen Harrap; Neil Poulter; Mark E Cooper; Mark Woodward; John Chalmers; Vlado Perkovic; Muh Geot Wong; Takashi Wada Journal: Kidney Int Rep Date: 2020-11-10