Early and exudative age‐related macular degeneration is associated with increased plasma levels of soluble TNF receptor II

Abstract

ABSTRACT.Purpose: We have recently identified homeostatic alterations in the circulating T cells of patients with age-related macular degeneration (AMD). In cultures of retinal pigment epithelial cells, we have demonstrated that T-cell-derived cytokines induced the upregulation of complement, chemokines and other proteins implicated in AMD pathogenesis. The purpose of this study was to test whether increased plasma levels of cytokines were present in patients with AMD. Methods: We conducted a case-control study. Age-related macular degeneration status was assessed using standardized multimodal imaging techniques. Plasma was isolated from freshly drawn peripheral venous blood samples and analysed for interleukin (IL)15, IL18, interferon (IFN)c, soluble tumour necrosis factor (TNF) receptor II (sTNFRII) and complement factor H (CFH) Y402H genotype. Results: We included 136 individuals with early or late forms of AMD and 74 controls. Significantly increased levels of sTNFRII were observed in patients with early or exudative AMD (p < 0.01). After adjusting for CFH Y402H genotype, age, sex and smoking history, the level of sTNFRII remained a significant predictor for prevalence of AMD with odds ratios at 3.0 in the middle and 3.6 in the highest tertiles. Levels of IL15, IL18 and IFNc were low and not associated with AMD. Conclusions: Increased plasma level of sTNFRII is found to be associated with AMD. The data supports the observations of low-grade, systemic inflammatory alterations in patients with AMD. However, it remains to be determined whether increased levels of TNFa can be found, which directly reflects an increased activity of macrophages and T cells.

Plasma markers of chronic low‐grade inflammation in polypoidal choroidal vasculopathy and neovascular age‐related macular degeneration

“…Apart from Faber et al. () and Haas et al. () which used ICGA for retinal diagnosis, other studies did not employ ICGA for diagnosis and some even based retinal diagnosis solely on fundus photography (Klein et al.…”

“…Instead of quantifying the labile cytokine TNF‐ α , we quantified the soluble TNF‐R2, which has a longer half‐life and is a more stable measure of the average TNF‐ α level (Faber et al. ). Cytokines were quantified using the commercially available U‐PLEX Human Assays™ (U‐PLEX, Meso Scale Diagnostics, Rockville, MD, USA).…”

Circulating biomarkers in glaucoma, age-related macular degeneration, and diabetic retinopathy

“…[58] Increased plasma level of soluble TNF-II was also found to be associated with AMD. [59] Lechner et al . have observed that circulating CD11b(+) cells and CD16 (hi) HLA-DR(−) neutrophils were found to be increased significantly in AMD patients when compared to controls.…”

New neovascular age‐related macular degeneration is associated with systemic leucocyte activity

“…; Faber et al. ; Haas et al. ), but whether these changes undergo change with time remains largely unknown.…”