ALW peptide ameliorates lupus nephritis in MRL/lpr mice

Huixia Wang,Kunyi Wu,Mei Lu,Lingling Peng,Yumin Xia,Siyue Zhai,Jie Yang

doi:10.1186/s13075-019-2038-0

Abstract

BackgroundLupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus. Anti-double-stranded (ds) DNA immunoglobulin G (IgG) plays a pivotal role in the pathogenesis of LN. Currently, there are various therapies for patients with LN; however, most of them are associated with considerable side effects. We confirmed previously that ALW (ALWPPNLHAWVP), a 12-amino acid peptide, inhibited the binding of polyclonal anti-dsDNA antibodies to mesangial cells and isolated glomeruli in vitro. In this study, we further investigate whether the administration of ALW peptide decreases renal IgG deposition and relevant damage in MRL/lpr lupus-prone mice.MethodsForty female MRL/lpr mice were randomly divided into four groups. The mice were intravenously injected with D-form ALW peptide (ALW group), scrambled peptide (PLP group), and normal saline (NaCl group) or were not treated (blank group). The IgG deposition, the histopathologic changes, and the expressions of profibrotic factors were analyzed in the kidney of MRL/lpr mice.ResultsCompared with the other groups, glomerular deposition of IgG, IgG2a, IgG2b, and IgG3 was decreased in the ALW group. Moreover, ALW administration attenuated renal histopathologic changes in MRL/lpr mice, including mesangial proliferation and infiltration of inflammatory cells. Furthermore, the expressions of profibrotic cytokines, such as transforming growth factor-beta1 (TGF-β1) and platelet-derived growth factor B (PDGF-B), decreased in the serum and kidney tissue of ALW-treated mice.ConclusionsOur study demonstrated that ALW peptide ameliorates the murine model of LN, possibly through inhibiting renal IgG deposition and relevant tissue inflammation and fibrosis.

Highlights

Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a large amount of autoantibodies and involvement of autoantibody-induced end-organ damage which is associated with significant morbidity and mortality [1]
ALW peptide decreases glomerular deposition of immunoglobulin G (IgG) in MRL/lpr mice Deposition of antibodies plays a pivotal role in the pathogenesis of LN

Summary

Introduction

Lupus nephritis (LN) is a common and serious complication of systemic lupus erythematosus. We confirmed previously that ALW (ALWPPNLHAWVP), a 12-amino acid peptide, inhibited the binding of polyclonal antidsDNA antibodies to mesangial cells and isolated glomeruli in vitro. Anti-double-stranded (ds) DNA antibody plays a crucial role in renal injuries by indirect and direct binding with glomerular antigens [2,3,4]. We found that the renal pathogenicity of anti-dsDNA IgGs (IgM, IgG1, IgG2a, IgG2b, and IgG3) was affected by the isotypes in a murine model [12, 13]. We identified a 12-amino acid peptide (ALWPPNLHAWVP [ALW]) that effectively inhibited the binding of all murine and human anti-dsDNA IgG subclasses to glomerular antigens [16]. ALW peptide markedly inhibited the affinity of murine and human lupus sera to dsDNA and glomeruli in vitro [16]. Through blocking the reactions of polyclonal anti-dsDNA antibodies to autoantigens in vivo, the ALW peptide (or its derivatives) may possibly be a helpful approach to depress the pathogenicity of anti-DNA antibodies

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