Background/Purpose: Recent studies found an high prevalence of varicella-zoster virus (VZV) infection in temporal arteries (TAs) from both temporal artery biopsy (TAB)-positive and TAB-negative giant cell arteritis (GCA) patients compared to controls, suggesting that VZV infection may trigger the inflammatory cascade that characterizes GCA (1,2). The aim of our study was to analyze VZV infection in TAs from patients with TAB-positive GCA (biopsy-proven GCA), TAB-negative GCA (patients with negative TAB and a final diagnosis of GCA) and controls (patients with negative TAB and a final diagnosis different from GCA).

Methods: 79 formalin-fixed, paraffin-embedded (FFPE) TABs performed between 2009 and 2012 from 34 TAB-positive GCA patients, 15 TAB-negative GCA patients and 30 controls were retrieved. Six 5-μm sections of all FFPE TABs were cut. The first section was analyzed by immunohistochemistry using a mouse monoclonal antiVZV glycoprotein E (gE) IgG1 antibody (Santa CruzBiotechnology, Dallas, TX) and UltraView DAB Detection Kit (Ventana, Roche, Tucson, Az.). DNA was extracted from the remaining 5 sections with the QIAamp DNA FFPE tissue kit (Qiagen) and analyzed by real-time polymerase chain reaction (PCR) for the presence of VZV with primers for the major DNA binding protein of VZV (ORF 29) using both the VZV ELITe MGB kit (CE-IVD assay) and the primers designed by Gilden et al (1,2). For 10 of the 34 TAB-positive GCA patients, a specimen of temporal artery longer than 2 mm obtained at the time of TAB and immediately stored frozen at -80°C was available. DNA was extracted from these 10 frozen specimens with the RNA/DNA/Protein purification kit (Norgen Biotek) and analyzed by PCR for the presence of VZV DNA. 30 additional 5-μm sections were cut from each of these 10 FFPE TABs for which the frozen specimens were available and analyzed by immunohistochemistry. A FFPE skin lesion from a patient with active infection with VZV was used as positive control.

Results: Immunohistochemical analysis detected VZV antigen in 1/34 (3%) TAB-positive GCA, 0/15 TAB-negative GCA and 0/30 controls, and in none of the 300 sections cut from the 10 FFPE TABs positive for GCA for which the frozen specimens were available. Instead VZV antigen was clearly detected in the skin lesion from a patient with active infection used as positive control. DNA obtained from all TABs was amplifiable. DNA obtained from frozen TABs was more concentrated than that obtained from FFPE TABs which allowed to load a higher quantity of DNA per reaction increasing assay sensitivity. VZV DNA was not detected in any of the FFPE TABs nor in frozen TABs, but was clearly detected in the FFPE skin lesion used as positive control. The histopathologic analysis showed transmural inflammation in all sections and no skip areas were found.

Conclusion: Our data do not support a role for VZV infection in the etiopathogenesis of GCA in Italian patients. References:1. Gilden D, et al. Prevalence and distribution of VZV in temporal arteries of patients with giant cell arteritis. Neurology. 2015 May 12;84(19):1948-55. 2. Nagel MA, et al. Analysis of Varicella-Zoster Virus in Temporal Arteries Biopsy Positive and Negative for Giant Cell Arteritis. JAMA Neurol. 2015 Nov 1;72(11):1281-7.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/no-detection-of-varicella-zoster-virus-in-temporal-arteries-of-patients-with-giant-cell-arteritis/