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64 Dysbiosis and gut barrier dysfunction in antiphospholipid syndrome as revealed by iga-seq profiling
  1. WJ Kim1,2,
  2. W Ruff2,
  3. C Aguiar3,
  4. A Yu2,
  5. SM Vieira2,
  6. JA Sterpka2,
  7. A Goodman4,
  8. D Erkan3 and
  9. MA Kriegel2,5
  1. 1Cheju Halla General Hospital, Laboratory Medicine, Jeju-si, Republic of Korea
  2. 2Yale School of Medicine, Immunobiology, New Haven, USA
  3. 3Hospital for Special Surgery, Medicine, NewYork, USA
  4. 4Yale School of Medicine, Microbial Pathogenesis, New Haven, USA
  5. 5Yale School of Medicine, Medicine, New Haven, USA

Abstract

Background and aims The antiphospholipid syndrome (APS) is an autoimmune thrombophilic non-gut disorder with high mortality. Various pathogens have been associated with transient antiphospholipid antibody production. We hypothesised that members of the gut microbiota in APS patients could represent a chronic trigger and exhibit heightened adaptive immune responses to the microbiota. The purpose of this study was to explore gut barrier function and faecal IgA-coated microbial composition in APS patients.

Methods Stool from 15 APS patients, 5 non-autoimmune thrombotic states, and 12 normal donors (total of 17 controls) was collected. Faecal homogenates were analysed for the gut permeability marker calprotectin and, in parallel, stained stained with PE-conjugated anti-human IgA prior to cell sorting. Faecal DNA was isolated and PCR-amplified targeting the V4 region of the 16S rRNA gene. Samples were sequenced on the Illumina MiSeq platform.

Results Faecal calprotectin and IgA-coated faecal bacterial levels were significantly higher in APS patients compared to controls (p<0.003; p<0.05). LEfSe analysis of IgA+ fractions showed that the strongest IgA-coated genus is Blautia in APS.

Conclusions These data suggest gut barrier dysfunction and aberrant IgA coating of commensals in APS. Markedly enhanced bacterial IgA coating in several APS patients supports a stronger adaptive immune response to the microbiota. Increased IgA coating of Blautia might reflect altered gut homeostasis as a Blautia species was shown to be part of proinflammatory IgA+ consortium in a recent study in IBD. To our knowledge, this study represents the first 16S rRNA profiling of IgA-coated gut commensals in patients with non-gut autoimmunity.

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