Jansen Valérie L B I, van Mourik Dagmar J M, Davids Mark, van Bergen En Henegouwen Kika, Noordermeer Tessa, Levels Johannes H M, Limper Maarten, Coppens Michiel, Nieuwdorp Max, Urbanus Rolf T, Middeldorp Saskia, van Mens Thijs E
Department of Vascular Medicine, Amsterdam UMC Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam Cardiovascular Sciences, Pulmonary Hypertension and Thrombosis, Amsterdam, The Netherlands.
TH Open. 2024 Aug 5;8(3):e308-e316. doi: 10.1055/s-0044-1788653. eCollection 2024 Jul.
The origin of autoantibodies in patients with antiphospholipid syndrome (APS) is unknown. The gut microbiome contributes to autoimmunity and contains peptide homologues to the main APS autoantigen, which affect disease activity in animal models. Alteration of the gut microbiota with vancomycin diminishes disease activity in mice but no data on the effect of gut microbiota alteration in APS patients are available to date. To evaluate whether the gut microbiome affects disease activity in human APS. This was a pre-post design intervention study in APS patients with stable disease and no gastrointestinal comorbidity. Subjects received oral vancomycin, 500 mg four times daily for 7 days, previously shown to alter gut microbiota composition without systemic effects. Disease activity was assessed at four time points by measuring a panel of clinical phenotype-related biomarkers: antiphospholipid antibodies (APLAs), complement and inflammation markers, and hemostatic parameters. The primary outcome was the composite of the biomarker panel determined by multilevel principal component analysis. A total of 15 subjects completed the study. The primary outcome, the first principal component of the biomarker panel data, was significantly different after 7 days of vancomycin treatment ( = 0.03), but not at day 42. APLA titers were unaffected. Unexpectedly, 4 out of 15 patients were negative for APLAs at baseline. In a post-hoc analysis, there was a prolonged effect for subjects with positive antibodies at baseline ( = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.
抗磷脂综合征（APS）患者自身抗体的起源尚不清楚。肠道微生物群与自身免疫有关，并且含有与主要APS自身抗原的肽同源物，这在动物模型中会影响疾病活动。用万古霉素改变肠道微生物群可降低小鼠的疾病活动，但迄今为止尚无关于改变肠道微生物群对APS患者影响的数据。
为了评估肠道微生物群是否影响人类APS的疾病活动。
这是一项针对病情稳定且无胃肠道合并症的APS患者的前后设计干预研究。受试者口服万古霉素，每日4次，每次500mg，共7天，先前已证明该剂量可改变肠道微生物群组成且无全身影响。通过测量一组与临床表型相关的生物标志物来评估四个时间点的疾病活动：抗磷脂抗体（APLA）、补体和炎症标志物以及止血参数。主要结局是通过多水平主成分分析确定的生物标志物组的综合指标。
共有15名受试者完成了研究。主要结局，即生物标志物组数据的第一主成分，在万古霉素治疗7天后有显著差异（P = 0.03），但在第42天没有差异。APLA滴度未受影响。出乎意料的是，15名患者中有4名在基线时APLA呈阴性。在事后分析中，基线时抗体呈阳性的受试者有延长的效应（P = 0.03）。在基线时APLA呈阴性的受试者中，干预没有效果。
肠道微生物群影响APS患者的生化疾病活动。其机制尚不清楚，但似乎具有APS特异性。
