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Impaired transglutaminase 2 expression in patients with systemic lupus erythematosus

全身性紅斑性狼瘡第二型轉麩胺酶的表現障礙

摘要


Objective: Transglutaminases are a group of enzymes that promote a transamination reaction, causing the cross-linking of proteins or the intercalation of polyamines. Tissue transglutaminase, also referred to as transglutaminase type 2 (TGM2), is a potentiating factor that is involved in cellular apoptosis and the formation of apoptotic bodies. The purpose of this study was to examine TGM2 expression in peripheral blood mononuclear cells (PBMCs) and analyze the correlations between TGM2 expression in PBMCs and clinical factors in patients with systemic lupus erythematosus (SLE). Method: Thirty-eight patients with SLE and 33 healthy volunteers were enrolled and assigned to the study group and control group, respectively. Results: The results of the study showed that the expression of TGM2 in PBMCs of patients with SLE was significantly higher than that of the controls. However, no statistically significant correlations with other clinical factors, including, age, disease activity, disease duration, and medication were found. The serological analysis revealed that TGM2 expression in SLE patients with ENA antibody was significantly lower, especially in patients with the RNP or Sm antibody. Conclusion: Previous studies showed that apoptotic cells induce TGM2 expression in macrophages and increase the phagocytosis of apoptotic cells. However, patients with SLE had a higher number of apoptotic cells and reduced phagocytosis. We postulate that the increased TGM2 expression in SLE patients is a compensatory phenomenon.

並列摘要


第二型轉麩胺酶是一種多功能蛋白,會造成蛋白的聚合或多胺類的嵌入的酵素,它們的交互作用已經被證實與細胞外鈣引入(Ca2+-influx)的分子機制有關。先前的研究也證實第二型轉麩胺酶是參與細胞凋亡及凋亡小體形成的潛在因子。這個研究的目的是要檢驗全身性紅斑性狼瘡患者,周邊血液單核球第二型轉麩胺酶表現量及與臨床表現關聯性。38位台中榮民總醫院過敏免疫風濕科門診病患及32位健康對照組參與此研究。取得受試者的血液樣本並分離出周邊血液單核球後,利用Trizol試劑來抽取細胞RNA,之後藉由反轉錄聚合酶反應將RNA轉錄為cDNA,將cDNA編碼至第二型轉麩胺酶和GAPDH特異性引子,再反轉錄聚合酶反應後用洋菜膠電泳呈現。研究結果顯示,全身性紅斑性狼瘡患者平均年紀為42.66±12.84歲,SLEDAI平均為2.63±2.42,全身性紅斑性狼瘡患者周邊血液單核球第二型轉麩胺酶表現量有顯著高於健康對照組。但是,其他的臨床因子,包括年紀、疾病活動度、病期及血清數據皆無統計學顯著相關。先前的研究顯示,周邊血液單核球第二型轉麩胺酶過度表現會強化細胞凋亡的速度。目前的研究結果尚且無法證實巨噬細胞吞噬能力低落的關連性,推測可能因此造成分化成巨噬細胞吞噬功能低落,更強化先前研究推論內在因素(intrinsic factor)影響的可能性,未來可能需要更多的研究分析證實其相關性。

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