Background/Purpose:
Giant cell arteritis (GCA) is a granulomatous vasculitis of large- and medium-sized arteries. An infectious organism has been hypothesized to cause GCA. We used 16S rRNA analysis to amplify a bacterial genomic sequence unique to the temporal arteries of GCA subjects. Identification of the bacteria allowed us to detect the organism’s lipopolysaccharide (LPS) in the serum of these subjects and isolate the bacteria from temporal arteries of GCA patients.
Methods:
Frozen and paraffin-embedded temporal arteries from biopsy-proven GCA subjects and controls were used for analysis. GCA subjects fulfilled the 1990 ACR criteria for GCA. DNA and RNA were isolated from frozen temporal arteries. 16S rRNA analysis was performed using primers to the conserved regions of bacterial 16S rRNA. Multilocus sequence typing (MLST), a PCR-based method of bacterial identification, was performed to type the organism. A Burkholderia anti-LPS monoclonal antibody was used to perform immunofluorescence (IF) and ELISA. Burkholderia was cultured from a temporal artery and the isolate was injected into C3H/HeSnJ mice. Infected mice were sacrificed and organs were analyzed by light microscopy for vasculitis. Student’s t-test was used to compare mean values.
Results:
16S rRNA analysis identified a genomic sequence within an affected artery that was 100% homologous to the genus Burkholderia. Primers specific for the bacteria identified the organism in 9/10 GCA arteries but in none of the controls (0/11). MLST analysis identified the organism as B. pseudomallei-like (BpGCA). RT-PCR confirmed the absence of type III secretion factors, a genetic profile that confers an attenuated phenotype for many species of Burkholderia. IF of paraffin-embedded temporal arteries identified BpGCA-LPS in GCA arteries but not controls. ELISA detected BpGCA-LPS at high levels in the serum of GCA subjects (n=61, mean 437.8 pg/ml, SEM 36.7) but not healthy controls (n=102, mean 28.1 pg/ml, SEM 3.8, p<0.0001). BpGCA was cultured from the temporal artery of a subject with GCA and the isolate was used to infect C3H/HeSnJ mice. Mice injected with the organism developed inflammation of pulmonary blood vessels.
Conclusion:
An attenuated newly identified species of Burkholderia has been isolated from temporal arteries of GCA subjects. LPS of the organism is detectable in the serum of GCA subjects. Mice infected with the organism develop vasculitis. BpGCA appears to be a critical factor in the pathogenesis of GCA.
Disclosure:
C. L. Koening,
None;
B. J. Katz,
None;
J. Hernandez-Rodriguez,
None;
M. Corbera-Bellalta,
None;
M. C. Cid,
None;
H. P. Schweizer,
None;
D. Li,
None;
J. Kaplan,
None;
G. S. Hoffman,
None;
I. De Domenico,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-a-burkholderia-like-strain-from-temporal-arteries-of-subjects-with-giant-cell-arteritis/