Immunology Department, Healthcare Research Institute, Hospital "12 de Octubre", Madrid, Spain.
Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
Front Immunol. 2019 Dec 23;10:2891. doi: 10.3389/fimmu.2019.02891. eCollection 2019.
The presence of anti-Beta 2 glycoprotein antibodies (aB2GP1) of IgA isotype is common in patients with functional impairment of the organs in which B2GP1 is elaborated. Pretransplant IgA aB2GP1 has been associated with increased risk of thrombosis in kidney and heart transplanted patients and has also been related with early mortality after heart transplantation. Circulating immune complexes between IgA and B2GP1 (B2A-CIC) have been described in the blood of patients positive for IgA aB2GP1 with thrombotic clinical symptoms. In kidney transplanted patients, B2A-CIC is a biomarker that predicts which patients IgA aB2GP1 positive are at risk of thrombosis events following kidney transplantation and may lead to early prophylactic treatment. The prevalence of B2A-CIC and its relation with outcomes after heart transplantation is not known. Follow-up study based on 151 consecutive patients who received a heart transplant. Autoantibodies and B2A-CIC were quantified in pre-transplant serum samples. Three groups of patients were followed-up for 2 years: Group-1, positive for IgA aB2GP1 and B2A-CIC ( = 19). Group-2, only positive for IgA aB2GP1 ( = 28). Group-0 (control group): IgA aB2GP1 negative ( = 104). Kaplan-Meir survival analysis showed that mortality in B2A-CIC positive was higher than group-0 at 3 months (HR:5.08; 95%CI: 1.36-19.01) and at 2 years (HR:3.82; 95%CI: 1.54-12.66). No significant differences were observed between group-2 and group-0. Multivariate analysis identified B2A-CIC as the most important independent risk factor for early mortality (OR = 6.12; 95% CI: 1.93-19.4). Post-transplant incidence of thrombosis was significantly higher in B2A-CIC positive patients than in the control group (OR: 6.42; 95%CI: 2.1-19.63). Multivariate analysis identified the presence of B2A-CIC (OR: 6.13; 95%CI: 2.1-19.63) and the pre-transplant habit of smoking actively (OR: 4.18; 95%CI: 1.35-12.94) as independent risk factor for thrombosis. The proportion of patients who had thrombotic events or died in the first trimester was significantly higher in group-1 (73.7%) than in group-0 (16.3%; < 0.001) and in group-2 (39.3%; = 0.02). Multivariate analysis identified B2A-CIC as the main independent risk factor for early outcomes (mortality or thrombosis) in the first 3 months after heart transplant (OR = 11.42, 95% CI: 1.69-9.68). B2A-CIC are a predictor of early mortality and thrombosis after heart transplant.
抗β 2 糖蛋白抗体（aB2GP1）的 IgA 同种型在 B2GP1 产生的器官功能障碍患者中很常见。移植前 IgA aB2GP1 与肾和心脏移植患者的血栓形成风险增加有关，并且与心脏移植后早期死亡率也有关。在 IgA 阳性且有血栓形成临床症状的患者的血液中已经描述了 IgA 和 B2GP1 之间的循环免疫复合物（B2A-CIC）。在肾移植患者中，B2A-CIC 是一种生物标志物，可以预测 IgA aB2GP1 阳性的患者在肾移植后发生血栓形成事件的风险，并且可能导致早期预防性治疗。B2A-CIC 的患病率及其与心脏移植后结局的关系尚不清楚。
这是一项基于 151 例连续接受心脏移植患者的随访研究。在移植前的血清样本中定量检测自身抗体和 B2A-CIC。对三组患者进行了为期 2 年的随访：组 1，IgA aB2GP1 和 B2A-CIC 均为阳性（n=19）；组 2，仅 IgA aB2GP1 阳性（n=28）；组 0（对照组）：IgA aB2GP1 阴性（n=104）。Kaplan-Meier 生存分析显示，B2A-CIC 阳性患者的死亡率在 3 个月（HR：5.08；95%CI：1.36-19.01）和 2 年（HR：3.82；95%CI：1.54-12.66）时高于组 0。组 2 与组 0 之间无显著差异。多变量分析确定 B2A-CIC 是早期死亡的最重要独立危险因素（OR=6.12；95%CI：1.93-19.4）。B2A-CIC 阳性患者移植后血栓形成的发生率明显高于对照组（OR：6.42；95%CI：2.1-19.63）。多变量分析确定 B2A-CIC（OR：6.13；95%CI：2.1-19.63）和移植前主动吸烟的习惯（OR：4.18；95%CI：1.35-12.94）是血栓形成的独立危险因素。组 1（73.7%）的患者在第一个 3 个月内发生血栓形成或死亡的比例明显高于组 0（16.3%；<0.001）和组 2（39.3%；=0.02）。多变量分析确定 B2A-CIC 是心脏移植后前 3 个月内早期结局（死亡或血栓形成）的主要独立危险因素（OR=11.42，95%CI：1.69-9.68）。
B2A-CIC 是心脏移植后早期死亡和血栓形成的预测因子。
