76. Gene expression profile of temporal artery tissue and whole blood in giant cell arteritis
Creators: name: Friedman1, Marcia
name: Albert2, Daniel
name: Dongseok Choi1,2,3,4
name: Stiefel2, Hillary
name: Oglesbee-Venghaus2, Colin
name: Harrington5, Christina A.
name: Wilson2, David J.
name: James T. Rosenbaum1,2,6
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Giant cell arteritis (GCA) is a systemic vasculitis affecting adults over age 50. Diagnosing GCA is notoriously challenging, as there are no reliable blood biomarkers and temporal artery biopsy (TAB) has a sensitivity of only approximately 80%. Thus, patients suffer both from missed diagnoses and over-treatment. This study seeks to identify differentially expressed transcripts in the blood and TAB of patients with GCA relative to controls, as determined by RNA-sequencing (RNA-Seq). <strong>Methods</strong>: Blood (PAXgene tubes) and formalin-fixed paraffin-embedded (FFPE) TAB tissue from patients undergoing TAB for suspected GCA were evaluated by RNA-Seq. Samples representative of biopsy positive GCA, biopsy negative GCA (negative biopsy but clinically diagnosed with GCA), polymyalgia rheumatica (PMR), non-vasculitic ischemia, other inflammatory diseases, and healthy controls (patients who underwent temporal artery biopsy but were not diagnosed with any disease) were included. Significantly differential expressed genes (DEGs) were considered as having a fold change (FC) &gt; 1.5 and a false discovery rate (FDR) &lt;0.05. Pathway analysis of significantly DEGs was performed using Reactome. Age, sex, and cumulative corticosteroid exposure pre-sample collection were included as covariates in the models. <strong>Results:</strong> 32 TAB and 27 whole blood samples were included in the analysis, including 8 biopsy positive GCA TABs and 5 biopsy positive GCA whole blood samples. (Fig. 1A) The majority of patients had glucocorticoid exposure pre-sample collection, and all samples were above age 50. TAB expression (Fig. 1B) of biopsy positive GCA TABs revealed 1493 up- and 681 down-regulated transcripts relative to control groups (healthy controls, non-vasculitic ischemic cardiovascular disease, PMR, and inflammatory controls). Skip lesions samples (n=2) overlapped substantially with biopsy positive GCA, despite being histologically unaffected. Biopsy negative GCA TAB gene expression did not show any DEGs relative to controls. Pathways significantly associated with biopsy positive GCA expression included innate immune pathways, interferon gamma and other cytokine signalling, PD-1, and integrin alphaIIb beta3 signalling, among others.Whole blood expression (Fig. 1C) showed 351 up- and 168 down-regulated transcripts relative to controls (healthy controls, cardiovascular disease, and PMR.) Biopsy positive GCA samples clustered together, however there was overlap with control groups. Biopsy negative GCA did not show any significant DEGs relative to healthy controls. Pathways associated with biopsy positive GCA DEGs included toll like receptor and MyD88 pathways, among others. <strong>Conclusions:</strong> The TAB gene expression signature distinguishes biopsy positive GCA from controls, while biopsy negative GCA tissue is not significantly different from controls. A preliminary analysis of skip lesions shows substantial overlap with biopsy positive GCA, which is surprising and suggests that skipped areas may represent early lesions, however this requires further evaluation. The lack of similarly between skip lesions and biopsy negative GCA calls into question the hypothesis that biopsy negative GCA is caused by skip lesions. Whole blood biopsy positive GCA gene expression shows fewer DEGs and an expression signature that overlaps with control groups. Whole blood expression in biopsy negative GCA is not substantially different from controls. Strengths include common GCA mimics as control groups (nonvasculitic ischemia and PMR) and the evaluation of both biopsy positive and biopsy negative GCA. Limitations include a small samples size and the difficulty in accurately diagnosing biopsy negative GCA. <strong>Disclosures:</strong> The authors believe that they have no relevant conflicts. <strong>Figure 1</strong>. Temporal artery biopsy and whole blood gene expression