Dataset Information

No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis.

ABSTRACT:

Background

To test the hypothesis that varicella-zoster virus (VZV) infection contributes to temporal arteritis pathogenesis, comprehensive in situ analysis was performed on temporal artery biopsies of 38 anterior ischemic optic neuropathy (AION) patients, including 14 (37%) with giant cell arteritis.

Methods

Biopsies were completely sectioned, and, on average, 146 serial sections per patient were stained for VZV glycoprotein E.

Results

Four of 38 AION patients showed VZV glycoprotein E staining, but VZV infection was not confirmed by staining for VZV IE63 protein and VZV-specific polymerase chain reaction on adjacent sections.

Conclusions

This study refutes the premise that VZV is casually related to AION with and without giant cell arteritis.

SUBMITTER: Verdijk RM

PROVIDER: S-EPMC7781446 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis.

Verdijk Robert M RM Ouwendijk Werner J D WJD Kuijpers Robert W A M RWAM Verjans Georges M G M GMGM

The Journal of infectious diseases 20210101 1

<h4>Background</h4>To test the hypothesis that varicella-zoster virus (VZV) infection contributes to temporal arteritis pathogenesis, comprehensive in situ analysis was performed on temporal artery biopsies of 38 anterior ischemic optic neuropathy (AION) patients, including 14 (37%) with giant cell arteritis.<h4>Methods</h4>Biopsies were completely sectioned, and, on average, 146 serial sections per patient were stained for VZV glycoprotein E.<h4>Results</h4>Four of 38 AION patients showed VZV g ...[more]

PMID: 32901261

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Project description:IntroductionHerpes zoster, which can have a major impact on quality of life, results from reactivation of a latent varicella zoster virus (VZV) infection. We hypothesized that giant cell arteritis (GCA) patients are at increased risk of herpes zoster because of treatment with high-dose glucocorticoids and advanced age. Aim of the study, therefore, was to determine cell-mediated and humoral immunity to VZV in patients with GCA, patients with closely related disease polymyalgia rheumatica (PMR; treated with lower doses of glucocorticoids) and healthy controls (HCs).MethodsCell-mediated immunity to VZV was determined by performing interferon-γ (IFNγ) enzyme-linked immunospot and intracellular cytokine flow cytometry measurements in 11 GCA and 15 PMR patients and in 26 age/sex-matched HCs. Immunoglobulin G antibodies to VZV glycoprotein (VZV-IgG) were measured in serum samples of 35 GCA and 26 PMR patients at different times of follow-up and in 58 age and sex-matched HCs by an enzyme-linked immunosorbent assay.ResultsThe number of VZV-specific IFNγ spot-forming cells was significantly lower in GCA patients on treatment, than in age-matched HCs (p = 0.029), but was not different in PMR patients on treatment. Similar levels of VZV-IgG were found in GCA and PMR patients at baseline, compared to HCs.ConclusionThe finding of a decreased cell-mediated immunity to VZV, known to be of great importance in defense to the virus, indicates an increased herpes zoster risk in GCA patients compared to an already at-risk elderly population. Herpes zoster vaccination is, therefore, of special importance in GCA patients, and would ideally be administered at time of diagnosis. Interestingly, as VZV was suggested to be the trigger in GCA pathogenesis, similar levels of VZV-IgG were found in GCA patients at time of diagnosis and age-matched HCs, indicating that GCA patients did not experience herpes zoster substantially more often in the months preceding diagnosis than controls.

Project description:Giant cell arteritis (GCA) is the most common systemic vasculitis in elderly individuals. Diagnosis is confirmed by temporal artery (TA) biopsy, although biopsy results are often negative. Despite the use of corticosteroids, disease may progress. Identification of causal agents will improve outcomes. Biopsy-positive GCA is associated with TA infection by varicella-zoster virus (VZV).To analyze VZV infection in TAs of patients with clinically suspected GCA whose TAs were histopathologically negative and in normal TAs removed post mortem from age-matched individuals.A cross-sectional study for VZV antigen was performed from January 2013 to March 2015 using archived, deidentified, formalin-fixed, paraffin-embedded GCA-negative, GCA-positive, and normal TAs (50 sections/TA) collected during the past 30 years. Regions adjacent to those containing VZV were examined by hematoxylin-eosin staining. Immunohistochemistry identified inflammatory cells and cell types around nerve bundles containing VZV. A combination of 17 tertiary referral centers and private practices worldwide contributed archived TAs from individuals older than 50 years.Presence and distribution of VZV antigen in TAs and histopathological changes in sections adjacent to those containing VZV were confirmed by 2 independent readers.Varicella-zoster virus antigen was found in 45 of 70 GCA-negative TAs (64%), compared with 11 of 49 normal TAs (22%) (relative risk [RR]?=?2.86; 95% CI, 1.75-5.31; P?<?.001). Extension of our earlier study revealed VZV antigen in 68 of 93 GCA-positive TAs (73%), compared with 11 of 49 normal TAs (22%) (RR?=?3.26; 95% CI, 2.03-5.98; P?<?.001). Compared with normal TAs, VZV antigen was more likely to be present in the adventitia of both GCA-negative TAs (RR?=?2.43; 95% CI, 1.82-3.41; P?<?.001) and GCA-positive TAs (RR?=?2.03; 95% CI, 1.52-2.86; P?<?.001). Varicella-zoster virus antigen was frequently found in perineurial cells expressing claudin-1 around nerve bundles. Of 45 GCA-negative participants whose TAs contained VZV antigen, 1 had histopathological features characteristic of GCA, and 16 (36%) showed adventitial inflammation adjacent to viral antigen; no inflammation was seen in normal TAs.In patients with clinically suspected GCA, prevalence of VZV in their TAs is similar independent of whether biopsy results are negative or positive pathologically. Antiviral treatment may confer additional benefit to patients with biopsy-negative GCA treated with corticosteroids, although the optimal antiviral regimen remains to be determined.

Project description:Anterior ischemic optic neuropathy (AION) can be divided into nonarteritic (NAION) and arteritic (AAION) forms. NAION makes up ~85% of all cases of AION, and until recently was poorly understood. There is no treatment for NAION, and its initiating causes are poorly understood, in part because NAION is not lethal, making it difficult to obtain fresh, newly affected tissue for study. In-vivo electrophysiology and post-mortem studies reveal specific responses that are associated with NAION. New models of NAION have been developed which enable insights into the pathophysiological events surrounding this disease. These models include both rodent and primate species, and the power of a 'vertically integrated' multi-species approach can help in understanding the common cellular mechanisms and physiological responses to clinical NAION, and to identify potential approaches to treatment. The models utilize laser light to activate intravascular photoactive dye to induce capillary vascular thrombosis, while sparing the larger vessels. The observable optic nerve changes associated with rodent models of AION (rAION) and primate NAION (pNAION) are indistinguishable from that seen in clinical disease, including sectoral axonal involvement, and in-vivo electrophysiological data from these models are consistent with clinical data. Early post-infarct events reveal an unexpected inflammatory response, and changes in intraretinal gene expression for both stress response, while sparing outer retinal function, which occurs in AAION models. Histologically, the NAION models reveal an isolated loss of retinal ganglion cells by apoptosis. There are changes detectable by immunohistochemistry suggesting that other retinal cells mount a brisk response to retinal ganglion cell distress without themselves dying. The optic nerve ultimately shows axonal loss and scarring. Inflammation is a prominent early histological feature. This suggests that clinically, specific modulation of inflammation may be a useful approach to NAION treatment early in the course of the disease.

Dataset Information

No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis.

Background

Methods

Results

Conclusions

Publications

No Evidence of Varicella-Zoster Virus Infection in Temporal Artery Biopsies of Anterior Ischemic Optic Neuropathy Patients With and Without Giant Cell Arteritis.

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