The Microbiome of Temporal Arteries.

Gary Stuart Hoffman,Pauline Funchain,Ted M Getz,Charis Eng,Madhav Sankunny,Alexandra Villa-Forte,Alexander Blandford,Gregory Kosmorsky,Julian D Perry,Leonard H Calabrese,Roshan Padmanabhan,Lisa Lystad,Alison H Clifford

doi:10.20411/pai.v4i1.270

Abstract

Objective:A role for microorganisms in giant cell arteritis (GCA) has long been suspected. We describe the microbiomes of temporal arteries from patients with GCA and controls.Methods:Temporal artery biopsies from patients suspected to have GCA were collected under aseptic conditions and snap-frozen. Fluorescence in situ hybridization (FISH) and long-read 16S rRNA-gene sequencing was used to examine microbiomes of temporal arteries. Taxonomic classification of bacterial sequences was performed to the genus level and relative abundances were calculated. Microbiome differential abundances were analyzed by principal coordinate analysis (PCoA) with comparative Unifrac distances and predicted functional profiling using PICRUSt.Results:Forty-seven patients, including 9 with biopsy-positive GCA, 15 with biopsy-negative GCA and 23 controls without GCA, were enrolled. FISH for bacterial DNA revealed signal in the arterial media. Beta, but not alpha, diversity differed between GCA and control temporal arteries (P = 0.042). Importantly, there were no significant differences between biopsy-positive and biopsy-negative GCA (P > 0.99). The largest differential abundances seen between GCA and non-GCA temporal arteries included Proteobacteria (P), Bifidobacterium (g), Parasutterella (g), and Granulicatella (g) [Log 2-fold change ≥ 4].Conclusion:Temporal arteries are not sterile, but rather are inhabited by a community of bacteria. We have demonstrated that there are microbiomic differences between GCA and non-GCA temporal arteries, but not between biopsy-positive and biopsy-negative GCA.

Highlights

Giant cell arteritis (GCA) is the most common large vessel vasculitis in adults, with an estimated incidence of 15-25 cases/100,000 among persons > 50 years old [1]
Sample Accrual and Collection We prospectively enrolled consecutive consenting patients undergoing temporal artery biopsy for evaluation of possible GCA, under a study protocol conducted in compliance with the Helsinki Declaration and approved by the Institutional Review Board at the Cleveland Clinic
Patients were classified according to clinical phenotype, including corticosteroid use, clinical symptoms, co-morbidities and histopathology results as either biopsy-positive GCA, biopsy-negative GCA, or as controls

Summary

Introduction

Giant cell arteritis (GCA) is the most common large vessel vasculitis in adults, with an estimated incidence of 15-25 cases/100,000 among persons > 50 years old [1]. Post-mortem and imaging studies have revealed that involvement of the aorta and its primary branch vessels is common, if not universal, in GCA [3,4,5]. In a post-mortem study of the aorta and primary branch vessels in 13 consecutive patients with GCA, all had features of vasculitis in spite of treatment with corticosteroids in 9 of 13 patients for several months to up to 9 years duration [3]. Patients with GCA usually respond quickly to treatment with high dose glucocorticoids, relapses occur frequently when doses are tapered, suggesting that the underlying driver of inflammation has not been addressed [6, 7]

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Results

Conclusion