An Intestinal Microbiome Intervention Affects Biochemical Disease Activity in Patients with Antiphospholipid Syndrome.

Background  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. Objective  To evaluate whether the gut microbiome affects disease activity in human APS. Methods  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. Results  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 ( p  = 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 ( p  = 0.03). In subjects with negative APLAs at baseline, the intervention showed no effect. Conclusion  The intestinal microbiome affects the biochemical disease activity in APS patients. The mechanism is yet unknown but appears to be APS-specific.
Competing Interests: Conflicts of Interest M.L. reports a research grant from GSK and consulting fees from GSK and AstraZeneca outside of the submitted work. M.C. has received financial support for research from Bayer, CSL Behring, Roche, UniQure, and Novo Nordisk; honoraria for consulting or lecturing from Alexion, Bayer, CSL Behring, Sobi, and Viatris. M.N. is founder and a member of the Scientific Advisory Board of Caelus Pharmaceuticals, The Netherlands; however, none of these possible conflicts of interest bear direct relations to the outcomes of this specific study. S.M. reports grants from GSK and Aspen; grants and personal fees from Daiichi-Sankyo, Bayer, Pfizer, and Boehringer Ingelheim; and personal fees from Portola/Alexion, AbbVie, Pfizer/Bristol-Meyers Squibb, Norgine, Viatris, and Sanofi, outside of the submitted work.
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