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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.

SUBMITTER: Li Z

PROVIDER: S-EPMC2631441 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Gene expression profiling in autoimmune noninfectious uveitis disease.

Li Zhuqing Z Liu Baoying B Maminishkis Arvydas A Mahesh Sankaranarayana P SP Yeh Steven S Lew Julie J Lim Wee Kiak WK Sen H Nida HN Clarke Grace G Buggage Ronald R Miller Sheldon S SS Nussenblatt Robert B RB

Journal of immunology (Baltimore, Md. : 1950) 20081001 7

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 expr ...[more]

PMID: 18802119

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Project description:ObjectiveWe sought to describe the risk and risk factors for hypotony in a noninfectious uveitis cohort.DesignRetrospective cohort study.ParticipantsPatients with noninfectious uveitis seen between 1979 and 2007 at 4 academic ocular inflammation specialty clinics.MethodsData were collected from medical records by trained, certified, expert reviewers.Main outcome measuresHypotony (<5 mmHg) and low intraocular pressure (<8 mmHg), each sustained for ? 2 visits spanning ? 30 days.ResultsDuring follow-up, 126 of 6785 patients (1.86%) developed hypotony at the rate of 0.61% (95% confidence interval [CI], 0.50-0.75%) per eye-year. Cataract surgery was associated with a 7.5-fold risk (adjusted hazard ratio [aHR], 7.51; 95% CI, 3.97-14.23) of incident hypotony. Phacoemulsification, the type of cataract surgery associated with the least hypotony risk still was associated with nearly 5-fold higher hypotony incidence (aHR, 4.87; 95% CI, 2.25-10.55). Increased risk was observed in children (aHR, 2.92; 95% CI, 1.20-7.10) with respect to young adults, and duration of uveitis of >5 years (aHR, 3.08; 95% CI, 1.30-7.31) with respect to uveitis of <6 month duration. Band keratopathy, ? 3+ vitreous cells, exudative retinal detachment, posterior synechia, and a history of pars plana vitrectomy also were associated with greater hypotony incidence. With respect to anterior uveitis, intermediate uveitis (aHR, 0.17; 95% CI, 0.05-0.56) and posterior uveitis (aHR, 0.11; 95% CI, 0.03-0.45) were associated with lower hypotony risk, whereas panuveitis (aHR, 1.25; 95% CI, 0.67-2.35) was similar. Approximately five-sixths (84.1%) of eyes presenting with hypotony had a visual acuity of ? 20/200 (aOR for visual acuity ? 20/200, 13.85; 95% CI, 7.23-26.53). Risk factors for prevalent hypotony were similar.ConclusionsThe risk of hypotony is low among eyes with noninfectious uveitis, but is more frequently observed in cases with anterior segment inflammation. Signs of present or past inflammation were associated with greater risk, suggesting excellent inflammatory control may reduce the risk of hypotony. Prior ocular surgery also was associated with higher risk; cataract surgery in particular was associated with much higher risk of hypotony. Lower risk of hypotony with phacoemulsification than with alternative cataract surgery approaches suggests the phacoemulsification approach is preferable.

Project description:ImportanceUveitis involves dysregulation of the ocular immune system. Stress has been shown to affect immune function, but it is unclear whether there is an association between stress and uveitis.ObjectiveTo determine whether having uveitis is associated with psychological stress.Design, setting, and participantsA cross-sectional, case-control study including a self-administered survey, medical records review, and diurnal salivary cortisol test was conducted at a university-based uveitis clinic and comprehensive eye clinic. Participants included 146 consecutive adults with noninfectious uveitis and age-matched controls with no eye disease. The study was conducted from December 1, 2017, to March 14, 2018.Main outcomes and measuresParticipants completed the self-administered, Cohen 10-item Perceived Stress Scale (PSS-10), a demographics questionnaire. Responses to each question were categorized on a 5-point Likert scale, with total scores ranging from 0 (no stress) to 40 (high stress). In addition, participants submitted 3 salivary cortisol samples. Those with uveitis were classified as having recently active or controlled disease through medical records review. The prespecified primary analysis was a linear regression of PSS-10 score and uveitis correcting for age, sex, educational level, employment, and median income. Secondary analyses included comparing PSS-10 scores in patients with recently active and controlled uveitis, determining predictors of stress, and comparing diurnal salivary cortisol between uveitis and control groups.ResultsOf 146 eligible patients, 17 declined participation and 9 consented but were excluded because they did not complete both questionnaires, resulting in 120 patients (80 uveitis; 40 controls) in the final analysis. Eighty participants (66.7%) were women, and 70 (58.3%) were white. Median age was 40 years (interquartile range, 29-59 years). Having uveitis was associated with a 4.3-point increase in PSS-10 score (95% CI, 1.8 to 6.9; P = .002). There was no significant difference in PSS-10 scores between patients with recently active and controlled uveitis (1.0 point greater for patients with active uveitis; 95% CI, -2.0 to 3.9; P = .52). Factors associated with increased PSS-10 score in patients with uveitis included female sex (coefficient, 4.0; 95% CI, 1.6 to 6.5; P = .002), current immunomodulatory therapy (coefficient, 2.5; 95% CI, -0.3 to 5.2; P = .08), history of depression (coefficient, 3.8; 95% CI, 0.8 to 6.8; P = .02), and having posterior or panuveitis (coefficient, 2.6; 95% CI, 0.8 to 4.4; P = .006). Of the 70 participants (58.3%) who had testable samples for cortisol analysis, diurnal salivary cortisol levels did not significantly differ between uveitis and nonuveitis groups.Conclusions and relevanceThese findings suggest that patients with uveitis have higher levels of psychological stress compared with controls, yet no significant difference was identified in the stress of patients with active vs controlled uveitis. Consequently, comprehensive treatment for noninfectious uveitis may be able to address the psychological results of this disease.

Project description:PurposeTo describe the risk and risk factors for ocular hypertension (OHT) in adults with noninfectious uveitis.DesignRetrospective, multicenter, cohort study.ParticipantsPatients aged ≥18 years with noninfectious uveitis seen between 1979 and 2007 at 5 tertiary uveitis clinics.MethodsDemographic, ocular, and treatment data were extracted from medical records of uveitis cases.Main outcome measuresPrevalent and incident OHT with intraocular pressures (IOPs) of ≥21 mmHg, ≥30 mmHg, and increase of ≥10 mmHg from documented IOP recordings (or use of treatment for OHT).ResultsAmong 5270 uveitic eyes of 3308 patients followed for OHT, the mean annual incidence rates for OHT ≥21 mmHg and OHT ≥30 mmHg are 14.4% (95% confidence interval [CI], 13.4-15.5) and 5.1% (95% CI, 4.7-5.6) per year, respectively. Statistically significant risk factors for incident OHT ≥30 mmHg included systemic hypertension (adjusted hazard ratio [aHR], 1.29); worse presenting visual acuity (≤20/200 vs. ≥20/40, aHR, 1.47); pars plana vitrectomy (aHR, 1.87); history of OHT in the other eye: IOP ≥21 mmHg (aHR, 2.68), ≥30 mmHg (aHR, 4.86) and prior/current use of IOP-lowering drops or surgery in the other eye (aHR, 4.17); anterior chamber cells: 1+ (aHR, 1.43) and ≥2+ (aHR, 1.59) vs. none; epiretinal membrane (aHR, 1.25); peripheral anterior synechiae (aHR, 1.81); current use of prednisone >7.5 mg/day (aHR, 1.86); periocular corticosteroids in the last 3 months (aHR, 2.23); current topical corticosteroid use [≥8×/day vs. none] (aHR, 2.58); and prior use of fluocinolone acetonide implants (aHR, 9.75). Bilateral uveitis (aHR, 0.69) and previous hypotony (aHR, 0.43) were associated with statistically significantly lower risk of OHT.ConclusionsOcular hypertension is sufficiently common in eyes treated for uveitis that surveillance for OHT is essential at all visits for all cases. Patients with 1 or more of the several risk factors identified are at particularly high risk and must be carefully managed. Modifiable risk factors, such as use of corticosteroids, suggest opportunities to reduce OHT risk within the constraints of the overriding need to control the primary ocular inflammatory disease.

Project description:PurposeTo characterize the risk and risk factors for intraocular pressure (IOP) elevation in pediatric noninfectious uveitis.DesignMulticenter retrospective cohort study.ParticipantsNine hundred sixteen children (1593 eyes) younger than 18 years at presentation with noninfectious uveitis followed up between January 1978 and December 2007 at 5 academic uveitis centers in the United States.MethodsMedical records review by trained, certified experts.Main outcome measuresPrevalence and incidence of IOP of 21 mmHg or more and 30 mmHg or more and incidence of a rise in IOP by 10 mmHg or more. To avoid underascertainment, outcomes were counted as present when IOP-lowering therapies were in use.ResultsInitially, 251 (15.8%) and 46 eyes (2.9%) had IOP ≥21 mmHg and ≥30 mmHg, respectively. Factors significantly associated with presenting IOP elevation included age of 6 to 12 years (versus other pediatric ages), prior cataract surgery, pars plana vitrectomy, duration of uveitis ≥6 months, contralateral IOP elevation, presenting visual acuity worse than 20/40, and topical corticosteroid use (in a dose-response relationship). The median follow-up was 1.25 years (interquartile range, 0.4-3.66). The estimated incidence of any observed IOP elevation to ≥21 mmHg, to ≥30 mmHg, and increase in IOP by ≥10 mmHg was 33.4%, 14.8%, and 24.4%, respectively, within 2 years. Factors associated with IOP elevation included pars plana vitrectomy, contralateral IOP elevation (adjusted hazard ratio [aHR], up to 9.54; P < 0.001), and the use of topical (aHR, up to 8.77 that followed a dose-response relationship; P < 0.001), periocular (aHR, up to 7.96; P < 0.001), and intraocular (aHR, up to 19.7; P < 0.001) corticosteroids.ConclusionsIntraocular pressure elevation affects a large minority of children with noninfectious uveitis. Statistically significant risk factors include IOP elevation or use of IOP-lowering treatment in the contralateral eye and local corticosteroid use that demonstrated a dose-and route of administration-dependent relationship. In contrast, use of immunosuppressive drug therapy did not increase such risk. Pediatric eyes with noninfectious uveitis should be followed up closely for IOP elevation, especially when strong risk factors such as the use of local corticosteroids and contralateral IOP elevation are present.

Dataset Information

Gene expression profiling in autoimmune noninfectious uveitis disease.

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Gene expression profiling in autoimmune noninfectious uveitis disease.

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