Elevated Serum Osteopontin Levels and Genetic Polymorphisms of Osteopontin Are Associated with Vogt-Koyanagi-Harada Disease

PURPOSE. Osteopontin (OPN) is a proinflammatory cytokine involved in chronic inflammatory diseases. This study aimed to analyze the role of OPN in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS. Serum levels of OPN in VKH patients and healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). Peripheral blood mononuclear cells (PBMCs) or CD4 (broken vertical bar) T cells were cultured with anti-CD3 and anti-CD28 antibodies in the absence or presence of recombinant OPN for the determination of cell proliferation and cytokines. Cell proliferation was detected using a cell counting kit. Levels of interferon (IFN)-gamma and interleukin (IL)-17 were detected by ELISA. Four single nucleotide polymorphisms (SNPs) of OPN and four SNPs of OPN receptors were genotyped in 601 VKH patients and 605 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS. OPN serum levels were significantly higher in patients with active VKH than in patients with inactive VKH and in healthy controls. PBMCs or CD4(+) T cells cultured with recombinant OPN induced a marked cell proliferation and profound secretion of IFN-gamma and IL-17 from patients with active VKH. A significantly increased frequency of the OPN rs4754 TT genotype (P = 0.004, pc = 0.048) was observed in VKH patients compared with healthy controls. No association could be detected among the four selected SNPs of OPN receptors and VKH. CONCLUSIONS. OPN may be relevant to the pathogenesis of VKH disease. The TT genotype of rs4754 may be a susceptible factor for VKH disease in a Chinese Han population. (Invest Ophthalmol Vis Sci. 2011;52:7084-7089) DOI:10.1167/iovs.11-753