Sjögren’s syndrome patients shares stereotypic B cell receptor clonotypes with distinct dysbiosis of the gut microbiome

Abstract

Purpose : Autoantibodies play a key role in Sjögren's syndrome (SS) in pathogenesis. Gut microbiomes are critical factors in shaping the B cell receptor (BCR) repertoire and show distinctive dysbiosis in SS patients. We aimed to find whether stereotypic B cell receptor clonotypes are shared among SS patients and their relations to gut microbiome.

Methods : In this prospective study, twenty SS patients who were diagnosed with American College of Rheumatology/European League Against Rheumatism classification criteria were enrolled. This study was adhered to the ethical standards of Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University College of Medicine (IRB number: 2005-117-1128, Seoul, South Korea). The patients who intake probiotics or antibiotics prior to joining a study were excluded. Corneal staining score and tear secretion were measured and peripheral blood and fecal samples were collected. BCR repertoires were constructed in silico using targeted amplicon sequencing of immunoglobulin genes. Clonality and sharing BCR repertoire were analyzed. Fecal microbiome was analyzed with 16S rRNA sequencing. Compositional abundance differences were identified using linear discriminant analysis (LDA) of effect size (LEfSe). Patients were divided into two groups based on the existence of each highly shared BCR clone. Then, we compared the microbiome composition in each group with distinct shared BCR sequences.

Results : All SS patients showed significant high corneal staining scores and less secretion of tear than healthy control did as previous reported. SS patients shared BCR clonotypes with significantly higher frequency compared to normal population, which were frequently IgA2 and harbored higher number of somatic mutations with distinct gut dysbiosis. Among the BCR clonotypes absent in the normal population extracted from the previous study, nine BCR clonotypes being shared by different sets of six to five patients showed to be an indicator for significantly higher frequencies of Bacteroides uniformis or Bacteroides cellulosilyticus.

Conclusions : It indicates that SS patients share stereotypic BCR clonotypes, decreasing clonal diversity and correlating with elevated frequencies of specific genera of gut microbiome and it may contribute to the pathogenesis of Sjögren's syndrome.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.