目的评估肾小球微血栓(GMT)在狼疮肾炎(LN)中的发生率,并探讨针对某些凝血相关因子的抗体和抗磷脂抗体在LN患者GMT形成中的临床意义。方法连续收集124例LN患者肾活检组织标本和血浆,观察组织标本中GMT的发生率,并分成LN—GMT组和LN—non—GMT组;比较两组患者的疾病活动度、相关实验室检查指标和肾组织活动/慢性指数;测定患者的狼疮抗凝物(LA)、抗心磷脂抗体(ACL)、抗β2糖蛋白Ⅰ(抗β2GPⅠ)抗体、抗凝血酶抗体、抗纤溶酶抗体、抗组织型纤溶酶原激活物(t-PA)抗体和抗膜联蛋白AⅡ(Annexin AⅡ)抗体。结果GMT在LN中的发生率约为20.2%;LN—GMT组系统性红斑狼疮疾病活动指数(SLEDAI)、肾组织病变活动指数、肾组织病变慢性指数、尿蛋白定量(24h)、血清肌酐、血清尿素氮的水平和高血压的发生率都较LN—non—GMT组高(P〈0.01);LN—GMT组LA、IgG型抗β2GPⅠ抗体和抗凝血酶抗体阳性率均显著高于LN-non—GMT组(P〈0.05);两组IgG型ACL抗体、抗纤溶酶抗体、抗t—PA抗体和抗Annexin AⅡ抗体阳性率差异均无统计学意义(P〉0.05);两组各抗体IgM型差异无统计学意义(P〉0.05)。结论LN中伴有GMT形成的患者肾脏病变重于无GMT者;LA、IgG型抗β2GPⅠ抗体和抗凝血酶抗体与LN患者GMT形成相关。
Objective To investigate the prevalence of glomerular microthrombosis in lupus nephritis (LN) and the significance of antibodies to anti-coagulation related factors and anti-phospholipid antibodies in glomerular microthrombosis (GMT). Methods Kidney biopsy specimens and plasma samples were obtained consecutively from 124 patients with LN. Kidney biopsy specimens were examined for the presence of glomerular microthrombi. Plasma samples from 25 LN patients with GMT (LN-GMT group) and 99 LN patients without GMT (LN-non-GMT group) were tested for lupus anticoagulant (LA) and antibodies to cardiolipin (ACL), β2 glycoprotein Ⅰ (β2GP Ⅰ ), plasmin, thrombin, tissue plasminogen activator (t-PA) and Annexin AⅡ. Results The prevalence of GMT in LN patients was about 20.2%. Compared to LN-non-GMT group, LN-GMT group had elevated SLE disease activity indices (SLEDAI), elevated activity and chronicity indices of kidney tissue injury, and elevated serum creatinine, blood urea nitrogen and proteinuria levels, and also had a higher frequency of hypertension (P〈0.01). The positive rates of LA, IgG class anti-β2GP Ⅰ and anti-thrombin antibodies were higher in LN-GMT group than in LN-non-GMT group (P〈0.05). The positive rates of IgG class antibodies to ACL, plasmin, t-PA and Annexin AⅡ in LN-GMT group were not statistically different from those in LN-non-GMT group (P〉0.05). No difference was found in the positive rate of any IgM class antibody between the two groups (P〉0.05). Conclusion This study has shown that GMT occurs approximately in 20.2% of the LN patients. Patients with GMT have more severe kidney tissue injury and more poor renal outcomes than patients without GMT. LA and antibodies to β2GP Ⅰ and thrombin play a role in glomerular microthrombosis in lupus nephritis.