Short communicationGene profiling involved in immature CD4+ T lymphocyte responsible for systemic lupus erythematosus
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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These authors equally contributed to this work.