CD3Z hypermethylation is associated with severe clinical manifestations in
systemic lupus erythematosus and reduces CD3?-chain expression in T cells
#MMPMID27940592
Hong KM
; Kim HK
; Park SY
; Poojan S
; Kim MK
; Sung J
; Tsao BP
; Grossman JM
; Rullo OJ
; Woo JM
; McCurdy DK
; Rider LG
; Miller FW
; Song YW
Rheumatology (Oxford)
2017[Mar]; 56
(3
): 467-476
PMID27940592
show ga
OBJECTIVE: The importance of hypomethylation in SLE is well recognized; however,
the significance of hypermethylation has not been well characterized. We screened
hypermethylated marks in SLE and investigated their possible implications.
METHODS: DNA methylation marks were screened in SLE whole-blood DNA by
microarray, and two marks ( CD3Z and VHL hypermethylations) were confirmed by a
methylation single-base extension method in two independent ethnic cohorts
consisting of 207 SLE patients and 151 controls. The correlation with clinical
manifestations and the genetic influence on those epigenetic marks were analysed.
RESULTS: Two epigenetic marks, CD3Z and VHL hypermethylation, were significantly
correlated with SLE: CD3Z hypermethylation (odds ratio = 7.76; P = 1.71 × 10 -13
) and VHL hypermethylation (odds ratio = 3.77; P = 3.20 × 10 -8 ), and the
increased CD3Z methylation was correlated with downregulation of the CD3?-chain
in SLE T cells. In addition, less genetic influence on CD3Z methylation relative
to VHL methylation was found in analyses of longitudinal and twin samples.
Furthermore, a higher CD3Z methylation level was significantly correlated with a
higher SLE disease activity index and more severe clinical manifestations, such
as proteinuria, haemolytic anaemia and thrombocytopenia, whereas VHL
hypermethylation was not. CONCLUSION: CD3Z hypermethylation is an SLE risk factor
that can be modified by environmental factors and is associated with more severe
SLE clinical manifestations, which are related to deranged T cell function by
downregulating the CD3?-chain.
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