title: Gene expression profiling in autoimmune noninfectious uveitis disease.
abstract: Noninfectious uveitis is a predominantly T cell-mediated autoimmune, intraocular inflammatory disease. To characterize the gene expression profile from patients with noninfectious uveitis, PBMCs were isolated from 50 patients with clinically characterized noninfectious 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 28 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 with 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 provide the first evidence that a subset of IL-10 family genes are implicated in noninfectious 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.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Li
authors.forename: Baoying
authors.initials: B
authors.lastname: Liu
authors.forename: Arvydas
authors.initials: A
authors.lastname: Maminishkis
authors.forename: Sankaranarayana P
authors.initials: SP
authors.lastname: Mahesh
authors.forename: Steven
authors.initials: S
authors.lastname: Yeh
authors.forename: Julie
authors.initials: J
authors.lastname: Lew
authors.forename: Wee Kiak
authors.initials: WK
authors.lastname: Lim
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
authors.forename: Grace
authors.initials: G
authors.lastname: Clarke
authors.forename: Ronald
authors.initials: R
authors.lastname: Buggage
authors.forename: Sheldon S
authors.initials: SS
authors.lastname: Miller
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014605:Uveitis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
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