s-adenosylhomocysteine and Purpura--Thrombocytopenic--Idiopathic

To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP).. 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.. 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).. 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.

Topics: Adolescent; Adult; Aged; Case-Control Studies; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; Female; Humans; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; RNA, Messenger; S-Adenosylhomocysteine; S-Adenosylmethionine; T-Lymphocytes; Young Adult

DNA methylation is known to play an important role in gene transcription and alterations of methylation contribute to the development of certain disorders such as cancer and immunodeficiency. Recent years have found an increasing interest in the role of epigenetic modifications in the etiology of human autoimmune diseases, such as systemic lupus erythromatosus (SLE) and rheumatoid arthritis (RA). DNA methyltransferases (DNMTs) are involved in the epigenetic control of DNA methylation processes. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, have important indicator action of cellular methylation status. The aim of this study is to explore if DNA methylation plays a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP).. DNMT1, DNMT3A, and DNMT3B mRNA expression in peripheral blood mononuclear cells (PBMCs) of adult ITP patients were analyzed by real-time quantitative polymerase chain reaction. Plasma SAM and SAH levels were assayed with reversed-phase high performance liquid chromatography (HPLC).. DNMT3A and DNMT3B mRNA expressions were significantly lower in ITP patients than in healthy controls (p < 0.001), while DNMT1 mRNA expression was not significantly different between the two groups (p = 0.774). Plasma SAH concentration was significantly elevated in ITP patients than in healthy controls (p < 0.05), while the plasma SAM and SAM/SAH were not significantly different between the two groups (p = 0.133, p = 0.624 respectively).. Our observations suggest that aberrant DNA methylation status reflected by increased plasma SAH concentration and decreased mRNA expression levels of DNMT3A and 3B are possibly involved in the pathogenesis of ITP although the precise mechanisms need further study.

Topics: Adolescent; Adult; Aged; Chromatography, High Pressure Liquid; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; S-Adenosylhomocysteine; S-Adenosylmethionine