[The role of DNA methylation in the pathogenesis of adult idiopathic thrombocytopenic purpura].

OBJECTIVE: To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP). METHODS: We measured DNA methyltransferases (DNMTs) 1, 3A and 3B mRNA expression in peripheral blood mononuclear cells of 48 adult ITP patients and 36 normal controls using real-time polymerase chain reaction, as well as the plasma levels of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) with reversed phase high performance liquid chromatography (HPLC). Furthermore, we determined the expression of CD(11a)/LFA-1 on CD(4)(+) or CD(8)(+) T cells by three-color flow cytometry. RESULTS: The mRNA expression of two DNA methyltransferases (DNMT3A and DNMT3B) was significantly lower when comparing ITP patients with healthy controls (P < 0.01). Although there were decreased tendency when comparing expression of DNMT1 of ITP patients with healthy controls, no significant differences were found (P > 0.05). The SAH concentration in the plasma of ITP patients was significantly elevated than that in the healthy controls (P < 0.05). However we found significant differences of SAM and SAM/SAH ratio in the plasma of ITP patients when compared with the healthy subjects (both P > 0.05). In addition, CD(11a)/LFA-1 expression on CD(8)(+) T lymphocytes increased in ITP patients compared with the control group (P < 0.01), whereas CD(11a)/LFA-1 expression on CD(4)(+) T lymphocytes and CD(4)(+)CD(11a)(+)/CD(8)(+)CD(11a)(+) ratio was significantly decreased in ITP patients than that in control group (both P < 0.01). CONCLUSION: Aberrant DNA methylation in peripheral blood and CD(11a)/LFA-1 expression on T cell surface may play an important role in the pathogenesis of ITP, although the underlying mechanisms still await further investigation.

Duke Scholars

Author Zhong Chen Pathology