Session Title: Vasculitis
Session Type: Abstract Submissions (ACR)
Background/Purpose: Whether infectious agents play a part in giant cell arteritis (GCA) remains controversial. We have performed the first microbiome study of snap-frozen temporal arteries, collected and processed under sterile conditions, from GCA patients and controls using metagenomic sequencing.
Methods: Patients undergoing temporal artery biopsy for possible GCA were prospectively enrolled. Biopsies were collected under strictly sterile conditions and split, with one part sent for routine histopathological review and one part snap-frozen for microbiome studies. Patients were classified according to clinical presentation as either biopsy-positive GCA (TA+), biopsy-negative clinically classical GCA (TA-) or controls. Long-read 16S ribosomal RNA (rRNA) sequencing was used to describe the entire microbiome of temporal arteries. Total DNA was isolated, and V1-V4 regions of the gene encoding bacteria-specific 16S rRNA were amplified and Sanger sequenced. Taxonomic classification of bacterial sequences was performed using an in-house analysis pipeline and relative abundances of species were calculated. Microbiomes were plotted by principal-coordinate analysis (PCoA) using a de novo operational taxonomic unit (OTU) picking protocol (using the MacQIIME 1.7 toolkit). Functional composition of microbiomes was analyzed using the PICRUSt bioinformatics package.
Results: Eleven patients were enrolled, including 3 TA+ GCA patients, 2 TA- GCA patients and 6 controls. All patients were receiving empiric prednisone therapy at time of biopsy and 1 control patient was also receiving doxycycline. Using PCoA, the microbiomes of control temporal arteries clustered tightly together in the center of the plot, showing high degrees of taxonomic relatedness, while GCA microbiomes (both TA+ and TA – patients) plotted in the periphery, clearly separated from controls. One control outlier was noted. Stratification of the samples by prednisone dosage did not account for the separation of GCA and controls on PCoA. Taxonomic classification revealed a wide variety of bacteria in each temporal artery (mean 10.8 species/control vs 10.6 species/GCA), with no overarching species common to all. Significant upregulation of 4 functional pathways (nucleotide metabolism, steroid hormone biosynthesis, biosynthesis of siderophore group nonribosomal peptides, and electron transport) was identified in the GCA microbiomes (both TA+ and TA-) as compared to controls.
Conclusion: Temporal arteries are not sterile. They are inhabited in both the control and diseased state by a community of bacteria. GCA temporal artery microbiomes (from both TA+ and TA- patients) differ from controls with respect to both the taxonomy and function of bacterial species present. Whether these shifts in the GCA microbiome represent the cause or effect of vascular inflammation remains to be elucidated.
* contributed equally to this work
G. S. Hoffman,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/temporal-artery-microbiome-in-giant-cell-arteritis/