Elsevier

Molecular Immunology

Volume 43, Issue 9, March 2006, Pages 1497-1507
Molecular Immunology

Short communication
Gene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus

https://doi.org/10.1016/j.molimm.2005.07.039Get rights and content

Abstract

We attempted to characterize the genes expression of CD4+ T lymphocytes for the pathogenesis of systemic lupus erythematosus (SLE). Genomewide gene expression profiles of CD4+ T cells, which were isolated from the disease severe activity (T4-1s) and nonactivity (T4-2s) with an SLE patient by using long serial analysis of gene expression (LongSAGE). We picked out 289 genes matching to Unigene cluster with different expression more than four copies between T4-1s and T4-2s libraries and analyzed their roles from the collectedly published articles of PubMed by genes functional clustering. The genes functions were related to a diverse cellular process including: (1) most of these genes were associated with CD4+ T cells functions, particularly related to cellular developments; (2) Ras pathway genes as RANBP10, GMIP, RASGRP2 and ARL5 might be responsible for the abnormal development of CD4+ T cells of SLE; (3) HIG2, TCF7, KHSRP, WWP1, SMAD3, TLK2, AES, CCNI and PIM2 belong to Wnt/beta-catenin way, they could play roles in modulating proliferation and differentiation of T lymphocytes; (4) uncertain viral infections may initiate autoimmunity because high levels expression genes were detected in T4-1s such as TRIM22, IER2, ABCE1, DUT, G1P2, G1P3, HNRPUL1, EVER2, IFNAR1, TNFSF14, TMP21 and PVRL2; and (5) apoptosis relating genes as EIF3S8, SH3BGRL3, GPX4, TOSO, PFDN5, BIN1, XIAPAF1, TEGT and CUGBP2 may contribute to over uploading of selfantigens in SLE cells. Abnormalities findings of multiple genes expression involving with a variety of CD4+ T cells process might be meaningful to understanding the pathogenesis of SLE, and immature CD4+ T cells may be responsible for SLE.

Introduction

Our understandings in animal models and in human patients have found that the pathogenesis of systemic lupus erythematosus (SLE) is associated with both genetic predispositions and environmental influences. This combination of various factors, which may differ among individuals, results in dysfunction of the adaptive immune system (Qing and Putterman, 2004). The production of autoantibodies immune complexes, along with autoreactive T lymphocytes mediate this altered immune response at the cellular level in SLE together cause pathological changes in several target organs, including skin, blood vessels, lung and kidney (Shlomchik et al., 2001). As SLE is a multigenic and age-dependent disease, the final disease phenotype is probably the result of many interactions arising from an initial loss of peripheral tolerance followed by the amplification of specific autoimmune responses. CD4+ T lymphocytes are considered to play a pivotal role in the generation of losing self-tolerance (Bouzahzah et al., 2003, Chang et al., 2004, Kolowos et al., 2001, Soltesz et al., 2002, Tsai et al., 2004).

A tremendous amount of work has been done to investigate the mechanisms underlying the pathogenesis of SLE. However, traditional molecular biology methods that focus on a single likely molecule or pathway may be limited in their ability to identify potential disease-related candidates from a broad spectrum of multiple interacting factors. Genomewide gene profiling using serial analysis of gene expression (SAGE) technology emerged in 1995 (Velculescu et al., 1995), and long serial analysis of gene expression (LongSAGE) were subsequently promoted in 2002 (Saha et al., 2002). LongSAGE derives 21 bp tags for a given transcript while SAGE generates 14 bp tags. A LongSAGE/SAGE library can produce adequate tags of transcripts which allow for the unbiased quantitative analysis of transcriptomes with given tissues or cells, but the LongSAGE tags can be used to rapidly identify novel genes and exons rather than SAGE tags. Although many aspects of T lymphocytes with SLE have been studied in detail, the molecular mechanisms underlying the pathogenesis of SLE for T cells remain elusive. This work is in an attempt to identify genes of T cells with SLE that determine commitment to the disease active state or nonactive state, the gene expression profiles of CD4+ T lymphocytes isolated from a SLE patient in the disease active state (T4-1s) and nonactive state (T4-2s) were analyzed by LongSAGE, which can detect novel genes and known genes that have not been implicated in CD4+ T cell with SLE so far.

Section snippets

Patient's selection and management

A 26-year-old woman who gave birth to a daughter four years ago was selected. The patient complained erythema eruptions on her hands, feet, back and face (see Supplementary data, Fig. s1) for five months along with arthropathy involving her shoulders, knees and coxae joints. The disease has not been identified and she did not take any medications until she was referred to our department. Laboratory examinations found that the patient was not with impaired renal, hepatic and cardiac function

Chemotherapy results and follow-up observations

Skin lesions showed on the patient's face, back, hands and feet at her first hospitalization (see Supplementary data, Fig. s1). The erythemas shrank along with chemotherapy and disappeared in the third hospitalization without relapse (see Supplementary data, Fig. s2). Red blood cells (RBC) count, white blood cells (WBC) count, erythrocyte sedimentation rate (ESR), 24 h protein of urine, C3, IgG, and antinuclear–antibodies (ANA) titer returned to normal levels (see Supplementary data, Figs. s3–s9

Acknowledgement

This work was supported by National Natural Science Foundation of China Grants (No. 30271199).

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