Elevated serum osteopontin levels and genetic polymorphisms of osteopontin are associated with Vogt-Koyanagi-Harada disease.

Abstract

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+ 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)-γ 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-γ 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.

• Authors: Mingliang Chu, Peizeng Yang, Ranran Hu, Shengping Hou, Fuzhen Li, Yuanyuan Chen, Aize Kijlstra
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 52 Issue 10 Pg. 7084-9 (Sep 09 2011) ISSN: 1552-5783 [Electronic] United States
• PMID: 21810982 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD28 Antigens
• CD3 Complex
• Cytokines
• Interleukin-17
• Recombinant Proteins
• Osteopontin
• Interferon-gamma

Topics

• Adult
• CD28 Antigens (immunology)
• CD3 Complex (immunology)
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Cytokines (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Genotype
• Humans
• Interferon-gamma (metabolism)
• Interleukin-17 (metabolism)
• Lymphocyte Activation
• Male
• Osteopontin (blood, genetics, pharmacology)
• Polymorphism, Single Nucleotide
• Recombinant Proteins (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Uveomeningoencephalitic Syndrome (blood, genetics)