A novel monoclonal antibody against human B7‑1 protects against chronic graft‑vs.‑host disease in a murine lupus nephritis model

Shen,Lijun; Zhu,Ying; Han,Lianhua; Wang,Yuyu; Yan,Tianming; Kong,Yong; Zou,Shitao; Qiu,Yuhua; Xu,Yan

doi:10.3892/etm.2020.9146

A novel monoclonal antibody against human B7‑1 protects against chronic graft‑vs.‑host disease in a murine lupus nephritis model

Authors:
- Lijun Shen
- Ying Zhu
- Lianhua Han
- Yuyu Wang
- Tianming Yan
- Yong Kong
- Shitao Zou
- Yuhua Qiu
- Yan Xu
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Affiliations: Institutes of Biology and Medical Sciences, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, P.R. China, Department of Immunology, Medical College, Soochow University, Suzhou, Jiangsu 215123, P.R. China, Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, P.R. China, Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215001, P.R. China
Published online on: August 25, 2020 https://doi.org/10.3892/etm.2020.9146
Article Number: 14
Copyright: © Shen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lupus nephritis (LN) is the most common complication that causes mortality in patients with systemic lupus erythematosus. The B7‑1/B7‑2 and CD28/cytotoxic T‑lymphocyte associated protein 4 co‑stimulatory pathway serves a key role in autoimmune disease and organ transplantation. The aim of the present study was to generate and characterize a monoclonal antibody (mAb; clone 4E5) against human B7‑1 and to investigate its potential use for the treatment of LN. The results demonstrated that the 4E5 mAb was successfully generated and able to recognize both human and mouse B7‑1. After injection of this mAb into a mouse model with chronic graft‑vs.‑host disease (cGVHD)‑induced lupus‑like disease, the expression of CD21, CD23, CD80 and CD86 on B220+ B‑cells in the spleen, and the concentrations of serum autoantibodies and urine protein, were decreased. Direct immunofluorescence analysis of the kidneys revealed that immunoﬂuorescence of immune complex deposits was weaker in the 4E5‑treated mice and electron microscopy analyses of renal tissues indicated that pathological injury of the kidneys of 4E5‑treated mice was decreased compared with that in the model control mice. The results of the present study demonstrated that inhibition of the B7‑1/CD28 co‑stimulatory signaling pathway with the 4E5 mAb may represent a promising strategy to decelerate the progression of LN that is induced by cGVHD with potential for use in the treatment of other autoimmune diseases.

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