Gene expression profiling in autoimmune non-infectious uveitis disease

• Published in: The Journal of immunology (1950) 2008-10, Vol.181 (7), p.5147-5157
• Main Authors: Li, Zhuqing, Liu, Baoying, Arvydas, Maminishkis, Mahesh, Sankaranarayana P., Yeh, Steven, Lew, Julie, Lim, Wee Kiak, Sen, H. Nida, Clarke, Grace, Buggage, Ronald, Miller, Sheldon S., Nussenblatt, Robert B.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606

Non-infectious uveitis is a predominantly T cell mediated autoimmune, intraocular inflammatory disease. To characterize the gene expression profile from patients with non-infectious uveitis, peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients with clinically characterized non-infectious uveitis syndrome. A pathway-specific cDNA microarray was used for gene expression profiling and real time PCR array for further confirmation. Sixty-seven inflammation and autoimmune associated genes were found differentially expressed in uveitis patients with twenty-eight of those genes being validated by real-time PCR. Several genes previously unknown for autoimmune uveitis, including IL-22, IL-19, IL-20 and IL-25/IL-17E, were found to be highly expressed among uveitis patients compared to the normal subjects with IL-22 expression highly variable among the patients. Furthermore, we show that IL-22 can affect primary human retinal pigment epithelial cells by decreasing total tissue resistance and inducing apoptosis possibly by decreasing phospho-Bad level. In addition, the microarray data identified a possible uveitis-associated gene expression pattern, showed distinct gene expression profiles in patients during periods of clinical activity and quiescence, and demonstrated similar expression patterns in related patients with similar clinical phenotypes. Our data provides the first evidence that a sub-set of IL-10 family genes are implicated in non-infectious uveitis and that IL-22 can affect human retinal pigment epithelial cells. The results may facilitate further understanding of the molecular mechanisms of autoimmune uveitis and other autoimmune originated inflammatory diseases.