Aqueous Cytokine Changes Associated with Posner-Schlossman Syndrome with and without Human Cytomegalovirus

Jing Li,Anita Sook Yee Chan,Chui Ming Gemmy Cheung,Henry Yang,Soon Phaik Chee,Samanthila Waduthantri,Maya Vania,Marcus Ang,Prosper N Boyaka

doi:10.1371/journal.pone.0044453

Abstract

AimTo study the differences in aqueous cytokines in Posner-Schlossman Syndrome (PSS) patients with and without human cytomegalovirus (CMV) DNA in the aqueous humor.MethodsThis is a prospective study. Fifty-three uveitis patients with clinical signs of PSS were enrolled and aqueous humor samples were collected. Fourteen PSS patients were positive of CMV DNA in the aqueous by polymerase chain reaction (PCR) analysis. These eyes were negative of common ocular pathogens such as herpes simplex virus, varicella-zoster virus, rubella virus and toxoplasma. Twenty-five otherwise healthy cataract patients were enrolled as controls. Cytokine concentration was measured by a magnetic color-bead-based multiplex assay and analyzed using statistical and classification approaches.ResultsThe average age of 53 PSS patients was 48.74±13.43 years (yrs) (mean ± standard deviation) and 66.3±15.0 yrs for the controls. The median CMV viral DNA copy number was 26000/mL aqueous (range 1400 to 85000 copies/mL) in 14 CMV positive patients as determined by quantitative PCR. PSS aqueous had significantly higher Interleukin (IL)-8 (CXCL8), monocyte chemotactic protein-1 (CCL2), macrophage inhibitory protein 1-β (CCL4), granulocyte colony-stimulating factor (GCSF) and transforming growth factor-β (TGF-β) levels than controls after adjusted by age and gender. IL-2, IL-12, tumor necrosis factor-α (TNF-α) and interferon-α (IFN-α) levels were significantly lower in PSS aqueous than controls. No difference between CMV positive PSS and CMV negative PSS aqueous was observed. Over 97% of PSS samples were distinguished from controls by elevated CXCL10 (>500 ng/mL), CXCL8 (>30 ng/mL) and CCL2 (>60 ng/mL) levels.ConclusionPSS eyes were characterized by elevated aqueous chemokine concentration. The presence of CMV viral DNA was not associated with significant change of the type of cytokine expression in PSS patients.

Highlights

It is estimated that about one-third of anterior uveitis is of unknown etiology despite having distinctive clinical features
In the context of high seroprevalence of human CMV infection, these findings suggest the possibility that intraocular human CMV reactivation or infection may be associated with the etiology of idiopathic uveitis in immunocompetent patients
Consecutive patients with clinical signs of Posner-Schlossman Syndrome presenting to the Singapore National Eye Centre (SNEC) Ocular Inflammation and Immunology Service from 1st January 2008 to 1st January 2010 were enrolled in the study

Summary

Introduction

It is estimated that about one-third of anterior uveitis is of unknown etiology despite having distinctive clinical features. Posner-Schlossman Syndrome (PSS) or glaucomatocyclitic crisis is typically characterized by recurrent episodes of elevated intraocular pressure (IOP), mild anterior chamber inflammation with a few keratic precipitates and rarely, heterochromia with anisocoria. Reactivation of CMV in immunocompetent humans has been increasingly recognized [4,5,6]. Such reactivation is usually limited to inflamed tissues and certain cancers. CMV reactivation in immunocompetent patients have been associated with stress [7], chronic inflammation [8,9] and the use of steroid [10,11]

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