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Published online before print March 14, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0107064

Received for publication January 25, 2007.
Revised February 8, 2007.
Accepted for publication February 9, 2007.

Article

Transcript overexpression of the MBD2 and MBD4 genes in CD4⁺ T cells from systemic lupus erythematosus patients

Research Unit in Systemic Autoimmune Diseases, Vall d’Hebron Research Institute, Hospital Vall d’Hebron, Barcelona, Spain

^@ To whom correspondence should be addressed. E-mail: jordi{at}vhebron.net.

	Abstract

Global DNA hypomethylation in CD4+ T cells has been detected in systemic lupus erythematosus (SLE), and it seems to be linked to its pathogenesis. We investigated the relationship between overall DNA methylation and the expression f two methyl CpG-binding domain (MBD) proteins. DNA deoxymethylcytosine (d^mC) content of purified CD4⁺ T cells from 29 SLE patients and 30 healthy controls was measured by means of an ELISA. Transcript levels of two methyl CpG-binding proteins (MBD2 and MBD4) were quantified by real-time RT-PCR. Association studies were also carried out with several laboratory parameters, as well as with the patients’ clinical manifestations. SLE patients had significantly less CD4+ T cell DNA d^mC content than controls (0.802±0.134 vs. 0.901±0.133; P=0.007). MBD2 and MBD4 mRNA levels were considerably higher in the patients’ group: 0.975 ± 0683 versus 0.604 ± 0.614 (P=0.004) and 0.359 ± 0.330 versus 0.092 ± 0.169, respectively (P<0.0005). It is interesting that SLE patients showed a negative correlation between methylation indices and MBD2 (r=-0.609, P<0.0005) and MBD4 (r=-0.395, P=0.034) transcript levels. MBD2 and MBD4 transcript overexpression and inverse correlations with DNA methylation indices indicate that both enzymes may really have a direct and active role on the genome-wide DNA hypomethylation observed in CD4+ T cells from SLE patients.

Key Words: DNA methylation • autoimmunity • epigenetics