183. MICROBIOME IN AORTITIS
Bibliographic record
Abstract
Background: Most non-infectious forms of aortitis are presumed to be autoimmune, resulting from primary systemic large vessel vasculitis (LVV), such as giant cell arteritis (GCA) or Takayasu’s arteritis (TAK) or other rheumatic diseases. Aortitis may also present as “clinically isolated aortitis” (CIA), a non- infectious vasculitis restricted to the aorta.1,2 It is not clear whether common conditions exist within CIA and GCA that contribute to inflammatory aneurysms; or how aortitis specimens compare to those from non-inflammatory thoracic aortic aneurysms. We have utilized sequencing of bacterial-specific 16S ribosomal RNA genes, a sensitive and culture-independent method for both pathogen and commensal detection, to characterize microbiomes of aortas affected by GCA and CIA and compared them to non-inflammatory aorta aneurysm controls. We also compared microbiomes of temporal arteries (TA) from a parallel study to those from aortic aneurysms. Methods: From 220 prospectively enrolled patients undergoing thoracic aorta aneurysm surgery, 49 were selected based on ability to match for age, gender and race (12 CIA, 14 GCA, and 23 non-inflammatory aneurysm controls). Biopsies were collected under surgically aseptic conditions, snap-frozen (-80oC), deidentified and processed at one time in blinded fashion. 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/DESeq2) and predicted functional profiling was performed with PICRUSt. Results: Microbial beta (p = 0.024) and alpha diversity (p = 0.018) differed between aortitis cases and controls. There were no significant differences between microbial communities in CIA and GCA (p > 0.7). The largest differential abundances between aortitis and non-inflammatory control samples included Actinobacteria (P), Actinomycetales (o), Klebsiella (g), Staphylococcus (g), and Propionbacterium (g) [2logfold>2]. Microbiomes of aortas differed significantly from those of TAs, in both the control and GCA groups (p = 0.0002). Conclusion: Thoracic aortic aneurysms are not sterile. GCA and CIA aneurysms share similar microbial communities, but differ from those found in TAs and non-inflammatory aortic aneurysms. Whether these distinctions play a role in the pathogenesis of aortitis or non-inflammatory aneurysms or reflect secondary alterations in tissue substrate is unknown. Disclosures: This work was supported, in part, by the Fasenmyer Clinical Immunology Center (to GSH, LC and CE), and the National Center for Advancing Translational Sciences (NCATS) of the NIH (UL1TR000439 to GSH).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".