Abstract:
PURPOSE:Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. METHODS:Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash(TM) methylated quantification colorimetric assay. RESULTS:Significant increase in DNMT3A (p < 0.001) was shown in lupus patients when compared to age-matched healthy controls. This increase was associated with a higher SLEDI index. More striking was that expression levels for African American (AA) women were higher than European American women in the lupus populations. A subset of AA women on DHEA therapy showed a significant decrease (p < 0.05) in DNMT3A expression in comparison to lupus patients not on the therapy. DHEA is an androgenic steroid found in low levels in the serum of lupus patients. Supplementation of this hormone has been shown to be beneficial to some lupus patients. DHEA was not shown to effect DNMT1 or DNMT3B expression. Increased expression was also noted in DNMT3B (p < 0.05) in lupus patients compared to age-matched healthy controls. However, no significant difference was noted in DNMT1 (p = 0.2148) expression between lupus patients and healthy controls. Although increases were detected in de novo methyltransferases, a global decrease (p < 0.001) in 5-methycytosine was observed in lupus patients when compared to age-matched healthy controls. CONCLUSION:These findings suggest that epigenetic changes may play a critical role in the manifestations of the disease observed among ethnic groups, particularly African American women who often have a higher incidence of lupus. DHEA therapy effects on DNMT3A expression in AA women warrant further investigation in a larger population.
journal_name
J Clin Immunoljournal_title
Journal of clinical immunologyauthors
Wiley KL,Treadwell E,Manigaba K,Word B,Lyn-Cook BDdoi
10.1007/s10875-012-9803-zsubject
Has Abstractpub_date
2013-02-01 00:00:00pages
342-8issue
2eissn
0271-9142issn
1573-2592journal_volume
33pub_type
杂志文章abstract::Immunoglobulin isolated from sera of homosexual men infected with human immunodeficiency virus (HIV) inhibited the reverse transcriptase (RT) activity of HIV. The inhibitory activity was specifically directed against HIV RT, and not against other mammalian retrovirus RT, including human T-lymphotropic virus type I. Th...
journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00915727
更新日期:1987-05-01 00:00:00
abstract:INTRODUCTION:Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes. Abnormal activation of intracellular signaling molecules in lymphocytes by inflammatory cytokines can instigate the inflammation in SLE. MATERIALS AND METHODS:The activation of e...
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
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journal_title:Journal of clinical immunology
pub_type: 杂志文章,多中心研究
doi:10.1007/s10875-016-0252-y
更新日期:2016-04-01 00:00:00
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
pub_type: 杂志文章,多中心研究
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更新日期:2014-05-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/BF00919143
更新日期:1983-01-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2011-06-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2019-02-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-014-0121-5
更新日期:2015-02-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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journal_title:Journal of clinical immunology
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2005-07-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 临床试验,杂志文章
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更新日期:2004-03-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
doi:10.1007/s10875-014-9990-x
更新日期:2017-02-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-008-9202-7
更新日期:2008-09-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2010-03-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2009-01-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
doi:10.1007/s10875-011-9646-z
更新日期:2012-06-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 已发布勘误
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更新日期:2019-07-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章,评审
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更新日期:1990-11-01 00:00:00
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journal_title:Journal of clinical immunology
pub_type: 杂志文章
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更新日期:2014-08-01 00:00:00