Altered fecal microbiome in birdshot chorioretinopathy compared to HLA-A29 positive healthy subjects

Abstract

Purpose : Birdshot chorioretinopathy (BSCR) is highly associated with HLA-A29 but the mechanism of this effect on disease remains unclear. HLA proteins are important mediators of immune responses and influence the gut microbiota which "educates" the immune system. We tested the hypothesis that the fecal bacterial composition is altered in individuals with BSCR compared to HLA-A29 positive healthy subjects.

Methods : Human subjects were consented under an approved IRB protocol. BSCR diagnosis was confirmed by medical record review. HLA-A29 status was determined by clinical lab review and/or HLA-A genotyping in the OHSU Immunogenetics Laboratory. Fecal samples were collected at home by each subject and either carried or express-shipped to our laboratory. Upon receipt, samples were frozen and stored at -80°C. The V4 region of the 16S rRNA gene was amplified from fecal DNA and sequenced using Illumina MiSeq. Sequencing data were processed using DADA2 and statistical analyses were performed in R. The non-parametric Wilcoxon rank sum test was used to compare groups.

Results : Twelve HLA-A29 positive Caucasian subjects were included: 5 healthy (3 female; median age 59 years) and 7 BSCR (6 female; median age 66 years). Statistically significant differences between groups were found by the Shannon and Pielou alpha diversity indices (Figure), but not by Inverse Simpson or number of observed genera (not shown). Furthermore, in BSCR the relative abundance of Firmicutes was increased and within that taxonomic lineage, the genus Roseburia was decreased (Figure).

Conclusions : Based on two measures of alpha diversity, we observed significant differences in the fecal microbiome composition of BSCR vs. HLA-A29 positive healthy subjects. We also found a higher abundance of the phylum Firmicutes and a decrease of Roseburia in BSCR. These data support our hypothesis that within the context of HLA-A29, BSCR is associated with alterations in the gut microbiota. Further research into how these alterations intersect with HLA-A29 specific peptidomic and additional genetic disease associations will advance our understanding of BSCR.

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

 

Significant fecal microbiome differences between BSCR (red) and HLA-A29⁺ healthy controls (HC, blue). Top: Alpha diversity by the Shannon (left) and Pielou (right) indices (both p=0.05). Bottom: Relative abundance of Firmicutes (left, p=0.006) and Roseburia (right, p=0.03).