title: Early and exudative age-related macular degeneration is associated with increased plasma levels of soluble TNF receptor II.
abstract: OBJECTIVE
  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)γ, 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 IFNγ 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 TNFα can be found, which directly reflects an increased activity of macrophages and T cells.
authors.affiliation: Department of International Health, Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark; Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Faber
authors.forename: Tina
authors.initials: T
authors.lastname: Jehs
authors.forename: Helene Baek
authors.initials: HB
authors.lastname: Juel
authors.forename: Amardeep
authors.initials: A
authors.lastname: Singh
authors.forename: Mads Krüger
authors.initials: MK
authors.lastname: Falk
authors.forename: Torben Lykke
authors.initials: TL
authors.lastname: Sørensen
authors.forename: Mogens Holst
authors.initials: MH
authors.lastname: Nissen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D017242:Complement Factor H / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005122:Exudates and Transudates; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D019409:Interleukin-15 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D057135:Wet Macular Degeneration / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; C493495:CFH protein, human; C569274:IL15 protein, human; C000589760:IL18 protein, human; D019409:Interleukin-15; D020382:Interleukin-18; D047889:Receptors, Tumor Necrosis Factor, Type II; D017242:Complement Factor H
keywords: age-related macular degeneration; cytokine; inflammation; plasma; sTNFRII