The Cytokine Interleukin-6 and the Chemokines CCL20 and CXCL13 Are Novel Biomarkers of Specific Endogenous Uveitic Entities.
The purpose of this study was to determine levels of the cytokines IL-1β, IL-6, IL-21, IL-22, and IL-23 and the chemokines CXCL13, CCL19, CCL20, and CCL21 in aqueous humor (AH) samples from patients with specific uveitic entities.



Paired serum samples (n = 13) and AH samples (n = 111) from patients with active idiopathic granulomatous uveitis (IGU) or with uveitis associated with HLA-B27-related inflammation, Behçet's disease (BD), Vogt-Koyanagi-Harada (VKH) disease, or sarcoidosis and control patients were analyzed in two different multiplex assays.



Cytokines IL-1β, IL-21, IL-22, and IL-23 were not detected in any AH sample. Chemokine CCL21 concentrations in serum were significantly higher than those in AH. CCL19 levels in AH and serum were not significantly different. Levels of CCL20 and CXCL13 in AH were significantly higher than those in serum. IL-6 was not detected in serum samples. IL-6 AH levels were significantly higher in patients with HLA-B27-associated uveitis and in BD patients than in patients with VKH disease, sarcoidosis, and IGU (P < 0.0001). CCL20 AH levels were significantly higher in HLA-B27-associated uveitis than in BD, VKH, sarcoidosis, and IGU (P = 0.001), whereas CXCL13 AH levels were significantly higher in VKH disease and IGU than in HLA-B27-associated uveitis, BD, and sarcoidosis (P = 0.007).



IL-6-driven immune responses are more potent in HLA-B27-associated uveitis and BD than in VKH disease, sarcoidosis, and IGU. CCL20 appears to be a specific biomarker of HLA-B27-associated uveitis, whereas CXCL13 appears to be a biomarker of VKH disease and IGU. Our findings suggest that IL-6, CCL20, and CXCL13 could serve as drug targets for treatment of specific clinical entities of endogenous uveitis.
Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia 2Dr. Nasser Al-Rashid Research Chair in Ophthalmology, King Saud University, Riyadh, Saudi Arabia.
Ahmed M
AM
Abu El-Asrar
Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Nele
N
Berghmans
Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Saleh A
SA
Al-Obeidan
Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Ahmed
A
Mousa
Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Ghislain
G
Opdenakker
Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Jo
J
Van Damme
Department of Microbiology and Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Sofie
S
Struyf
D001082:Aqueous Humor / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D054418:Chemokine CCL20 / Q000378:metabolism*; D054382:Chemokine CXCL13 / Q000378:metabolism*; D015796:HLA-B27 Antigen / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D011379:Prognosis; D012720:Severity of Illness Index; D014605:Uveitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; C108355:CCL20 protein, human; C110663:CXCL13 protein, human; D054418:Chemokine CCL20; D054382:Chemokine CXCL13; D015796:HLA-B27 Antigen; C508600:IL6 protein, human; D015850:Interleukin-6