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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.

A precipitating antigen-antibody system has been characterized that occurs in patients with polymyositis. At least half of the patients not only have polymyositis but also have scleroderma. The proposed name for this antigen found in calf thymus extract (CTE) is PM-Scl, to indicate the almost universal presence of polymyositis and the frequent occurrence of scleroderma in the patients who make antibodies to this antigen. The antigen is probably nucleolar since all sera which precipitate with the PM-Scl antigen stain the nucleoli of Hep2 cells by indirect immunofluorescence. The PM-Scl immune system is a distinctive one different from the other known precipitins that occur in patients with polymyositis and dermatomyositis including Jo1, nRNP, and Mi. This PM-Scl antigen and its antibody represent one system which constitutes part of the reactions previously designated as PM1. Interlaboratory exchange of sera and extracts have established the unique nature of this reaction which occurs in patients with inflammatory myopathy.