Antiphospholipid syndrome: potential link between the gut and autoimmunity

Antiphospholipid syndrome (APS) is an autoimmune disease of unclear etiology. Its estimated prevalence is 50 patients per 100,000 individuals and is caused by self targeting antiphospholipid antibodies that lead to an increased risk of thrombosis. Genetically predisposing factors are known, yet alone, cannot be decisive for the onset and severity of APS. Ruff et al., Cell Host Microbe, 2019, found that the gut microbiome is likely to be implicated in the development and persistence of autoimmunity in APS. They demonstrated cross-reactivity between non-orthologous mimotopes present in DNA methyltransferase (DNMT) expressed by a common human gut commensal Roseburia intestinalis and T and B cell autoepitopes in the APS autoantigen β2-glycoprotein I (β2GPI).

Here we sequenced 79 stool microbiome samples from 19 APS patients and 16 healthy donors at nearly 100 million median number of reads, obaining a first ever metagenomic dataset for APS. We compare alpha- and beta-diversity between disease and healthy individuals and investigate previously identified R. intestinalis, as well as other known microbiome cardiolipin producers finding no differences. We search for proteins carrying the β2GPI autoepitopes via database search and direct search in the sequenced reads leading to discovery of many more potential epitope carriers needing further experimental confirmation.