Increased Expression of Ganglioside GM1 in Peripheral CD4+ T Cells Correlates Soluble Form of CD30 in Systemic Lupus Erythematosus Patients

Lingli Dong,Hisanori Umehara,Shaoxian Hu,Wei Sun,Yikai Yu,Fang Chen,Xiaomei Lei,Liu Yang,Wei Tu,Yasufumi Masaki,Takuro Yamaguchi

doi:10.1155/2010/569053

Abstract

Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts) with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4) were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30), IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores). Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE.

Highlights

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune, connective-tissue disorder in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes [1]
Analyzing the correlations among the SLE patients, we found that there was a significant correlation between GM1 expression on CD4+ T cells (MFI), SLE Disease Activity Index (SLEDAI) scores(r = 0.556, P < .005), plasma level of SCD30 (r = 0.51, P < .005), and serum IgG levels (r = 0.56, P < .005) in the SLE patients
Number of GM1-highly expressing CD45RO+CD4+ memory T cells were significantly increased in SLE patients compared with healthy controls (Figure 2(e))

Summary

Introduction

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune, connective-tissue disorder in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes [1]. Lipid rafts are liquid ordered sphingolipid and cholesterol-enriched membrane domains, functioning in cellular processes, especially in signal transduction through recruiting signaling and stimulatory proteins [4], and play a critical role in T lymphocytes activation, in signaling from the T-cell antigen receptor (TCR) and in localization and function of proteins residing proximal to the receptor [4,5,6,7]. High levels of GM1 and cholesterol have been found in peripheral blood T cells from SLE patients, which was only measured in whole negatively selected T cells population by confocal microscopy study [9]. The levels of GM1 in T cell subgroups such as CD4+ helper T cells and CD8+ cytotoxic T cells are largely unknown

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Conclusion