Pediatric Uveitis and Scleritis in a Multi-Ethnic Asian Population.

Purpose: To describe the demographics and clinical characteristics of pediatric uveitis and scleritis at a tertiary eye care center.Methods: Clinical records of children with either uveitis or scleritis that presented between January 1989 and January 2016 were reviewed retrospectively.Results: Seventy-three patients were identified. Fifty-four had uveitis and 19 had scleritis. Posterior uveitis was the most common (27.8%), followed by intermediate uveitis (25.9%), panuveitis (25.9%) and anterior uveitis. Majority were noninfectious uveitis (37.0%), and 29.6% were idiopathic. Common associations were sarcoidosis (14.8%), HLA-B27 haplotype (9.3%) and toxoplasmosis (7.4%). Posterior scleritis was more common (94.7%) than anterior scleritis and majority were idiopathic (68.4%). Delayed patient presentation and presenting visual acuity worse than 0.3 LogMAR were associated with poor visual outcome (p = .03; OR = 0.17; 95% CI, 0.03-0.84 and p = .007; OR = 0.09; 95% CI, 0.02-0.52 respectively).Conclusion: Majority had noninfectious etiologies. Uveitis associated with juvenile idiopathic arthritis was rare.

Prevalence and clinical features of systemic diseases in Chinese patients with uveitis.

PURPOSE: Systemic diseases are frequently associated with uveitis but are often not recognised by clinicians. An estimate of the prevalence in a large-scale uveitis population is essential for understanding the epidemiological profile and may be helpful for clinical practice. DESIGN: A nationwide survey. METHODS: Data were obtained from a national database which included the registration of uveitis cases from 23 provinces, 5 autonomous regions and 4 municipalities across mainland China. The primary outcome was identification of a systemic disease associated with uveitis. RESULTS: From April 2008 through August 2018, 15 373 uveitis patients were included in the study. Males accounted for 52.9%, and the mean (SD) age of uveitis onset was 35.4 (15.9) years. After standardisation for age, the prevalence of systemic disease among patients with uveitis was 30.8% (95% CI, 30.1% to 31.6%). Vogt-Koyanagi-Harada disease (VKH; age-standardised prevalence, 12.7%; 95% CI, 12.1% to 13.2%), Behçet's disease (BD; 8.7%; 95% CI, 8.3% to 9.2%), ankylosing spondylitis (AS; 5.0%; 95% CI, 4.6% to 5.3%) and juvenile idiopathic arthritis (JIA; 1.2%; 95% CI, 1.0% to 1.3%) were the most common entities among 36 different forms of systemic diseases identified. The prevalence was significantly higher in males (37.0%; 95% CI, 36.0% to 38.1%) than in females (23.6%; 95% CI, 22.6% to 24.6%), and also higher in bilateral uveitis patients (41.2%; 95% CI, 40.2% to 42.2%) compared with unilateral cases (14.3%; 95% CI, 13.4% to 15.2%), and was highest in panuveitis (59.5%; 95% CI, 58.2% to 60.8%). CONCLUSION: Approximately one third of uveitis patients in this nationwide survey have an associated systemic disease, whereby VKH, BD, AS and JIA are the most frequent entities seen in China.

Genetic aspects of idiopathic paediatric uveitis and juvenile idiopathic arthritis associated uveitis in Chinese Han.

BACKGROUND: Idiopathic paediatric uveitis (IPU) and juvenile idiopathic arthritis associated uveitis (JIA-U) are the two most common entities in paediatric uveitis. This study addressed the possible association of IPU and JIA-U with genes that had been shown earlier to be associated with juvenile idiopathic arthritis. METHODS: We carried out a case-control association study involving 286 IPU, 134 JIA-U patients and 743 healthy individuals. A total of 84 candidate single nucleotide polymorphisms (SNPs) in 60 genes were selected for this study. The MassARRAY platform and iPLEX Gold Genotyping Assay was used to genotype 83 candidate SNPs and the remaining SNP (rs27293) was analysed using the TaqMan SNP Genotyping Assay. RESULTS: No evidence was found for an association of the candidate polymorphisms tested with IPU. Six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) showed an association with JIA-U (p<1.0×10-2). CONCLUSION: Our findings showed associations of six SNPs (PRM1/rs11074967, JAZF1/rs73300638, IRF5/rs2004640, MEFV/rs224217, PSMA3/rs2348071 and PTPN2/rs7234029) with JIA-U. No association was detected between the 84 tested SNPs and IPU.

Association of apoptosis genes in PDCD1 but not PDCD1LG2, FAS, and FASLG with pediatric idiopathic uveitis in Han Chinese.

BACKGROUND: Previous studies have shown that aberrant T lymphocyte apoptosis is involved in the pathogenesis of uveitis. Genetic variants of apoptotic pathway-related factors (including PDCD1, PDCD1LG2, FAS, and FASLG) may affect apoptosis and in turn predict susceptibility to autoimmune disease. This has not yet been studied in pediatric idiopathic uveitis (PIU) and juvenile idiopathic arthritis (JIA)-associated uveitis and was therefore the subject of the study presented here. METHODS: Fourteen single-nucleotide polymorphisms (SNPs) of several apoptosis-related pathway genes were analyzed in 1238 PIU patients, 128 JIA-associated uveitis patients and 1114 healthy controls using the iPLEX Gold Assay and MassARRAY platform. RESULTS: A lower frequency of the PDCD1/rs6710479 CC genotype in PIU patients was found when compared to controls (Pc = 3.42 × 10-3). A higher frequency of the PDCD1/rs7421861 A allele (Pc = 4.85 × 10-3) was observed in PIU patients as compared with controls. Stratification analysis showed a positive association of band keratopathy with the PDCD1/rs7565639 CT genotype (Pc = 1.05 × 10-2) and a negative association of this parameter with the PDCD1/rs7565639 C allele (Pc = 3.76 × 10-2). CONCLUSIONS: This study revealed that rs6710479 and rs7421861 in the PDCD1 gene confer susceptibility to PIU in Han Chinese. A stratified analysis showed that PDCD1/rs7565639 is associated with band keratopathy in PIU patients.

Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis.

OBJECTIVE: To determine the ophthalmological and extra-ophthalmological clinical characteristics and visual prognosis of patients with sarcoid uveitis in different ethnic groups. METHODS: We retrospectively analysed the data from patients with sarcoid uveitis seen at two departments of Ophthalmology between December 2003 and December 2017. Patients presented biopsy-proven sarcoidosis and/or presumed sarcoid uveitis based on the following criteria: compatible thoracic imaging, associated with elevated angiotensin-conversion enzyme (ACE) and/or lymphocytic alveolitis on bronchoalveolar lavage fluid analysis (> 15% lymphocytes and CD4/CD8 > 3.5). Ophthalmological and general characteristics, as well as visual and global prognoses, were compared in three pre-defined ethnic groups: White Europeans, North Africans and Afro-Caribbeans. RESULTS: A total of 194 patients were included: 145 with biopsy-proven and 49 with presumed sarcoid uveitis. Overall, 68% were White Europeans while 20.6% were North Africans and 11.3% were Afro-Caribbeans. Sixty-nine per cent were women and the median age at presentation was 52.1 years. Median ages at first ocular manifestation of the disease in Afro-Caribbeans and North Africans were respectively 34.3 and 43.1 years, while it was 57.8 years in White Europeans (p < 0.001). Ocular involvement was bilateral in 77.8% (n = 151) of the cases and nearly half of the patients had panuveitis (48.5%). Anterior uveitis was more frequent in Afro-Caribbeans (59.1%; p < 0.0001), while White Europeans presented more frequently with intermediate uveitis. There was a significantly higher frequency of systemic involvement of sarcoidosis in North Africans while White Europeans showed a higher frequency of isolated ocular involvement at onset and during follow-up. Afro-Caribbeans, who had a complete visual recovery in 72.7% of the cases, had a better visual prognosis than other ethnic groups (p = 0.025). CONCLUSION: In this large European series of sarcoid uveitis, we observed ethnicity-related differences regarding uveitis clinical presentation and visual outcome. Although good overall, the visual prognosis seems to be better in Afro-Caribbeans than in other ethnic groups.

Choroidal Thickness in Patients Diagnosed with Human Immunodeficiency Virus Infection: Results from Two Populations of Different Ethnicities.

Purpose: To measure the choroidal thickness among subjects with human immunodeficiency virus (HIV) infection from two diverse ethnic populations and to compare it with healthy controls. Methods: Subjects with HIV infection and healthy controls were enrolled in two referring centers in Italy and India. Clinical data were collected. All subjects underwent enhanced-depth imaging optical coherence tomography and measurement of choroidal thickness. Results: A total of 68 eyes from 68 patients with HIV (44 Caucasian, 24 Indians) and 60 eyes from 60 healthy volunteers (36 Caucasian, 24 Indians) were included. Mean choroidal thickness was significantly higher in HIV patients compared to controls (312.91 ± 65 µm vs. 266.57 ± 47 µm; p < 0.001). Choroidal thickness was higher among subjects with HIV-related retinopathy compared to HIV without retinopathy (285 ± 30 µm vs. 352 ± 17 µm; p < 0.01). Conclusions: Patients with HIV infection, especially with HIV microangiopathy, have thicker choroid compared to age- and gender-matched healthy control subjects. These changes may be related to HIV-associated choroidal vascular dysfunction.

The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the Treatment of Uveitis.

Purpose: To detect any correlation between race and sex and the side effects of methotrexate in uveitis treatment. Methods: Retrospective review of patients seen at Northwestern Memorial Hospital between August 2012 and September 2014 with a history of MTX treatment for uveitis. Demographic, treatment, and side-effect data were collected for each patient. Results: Ninety-seven patients were included (25 males, 72 females). Twenty-eight patients reported African American race, 60 reported Caucasian race, and the remaining 9 reported Asian, Hispanic, or Arabic ethnicity. Males experienced more gastrointestinal upset than females (24% versus 13.8%). Caucasians had more gastrointestinal complaints (20% versus 8%) while African Americans developed more hair loss (14% versus 6.6%), although the numbers were too small to detect a statistical difference. Conclusion: While our sample was small, these findings suggest racial and gender disparities in the side effects experienced by patients treated with methotrexate. This information may be useful to clinicians counseling patients on risk profile.

Epidemiology of uveitis (2013-2015) and changes in the patterns of uveitis (2004-2015) in the central Tokyo area: a retrospective study.

BACKGROUND: The distribution of uveitis varies with genetic, ethnic, geographic, environmental, and lifestyle factors. Epidemiological information about the patterns of uveitis is useful when an ophthalmologist considers the diagnosis of uveitis. Therefore, it is important to identify the causes of uveitis over the years in different regions. The purposes of this study were to characterize the uveitis patients who first arrived at the University of Tokyo Hospital in 2013-2015, and to analyze the changes in the patterns of uveitis from 2004 to 2012 to 2013-2015. METHODS: We retrospectively identified 750 newly arrived patients with uveitis who visited the Uveitis Clinic in the University of Tokyo Hospital between January 2013 and December 2015, using clinical records. We extracted data on patient age, sex, diagnosis, anatomic location of inflammation, laboratory test results of blood and urine, and chest X-ray and fluorescein fundus angiography findings for each patient. In addition, we compared these data with those from 2004 to 2012 to analyze the changes in the patterns of uveitis. RESULTS: A definite diagnosis was established in 445 patients (59.3%). The most common diagnoses were herpetic iridocyclitis (7.5%), sarcoidosis (6.1%), Behçet's disease (4.4%), Vogt-Koyanagi-Harada disease (4.1%), and intraocular lymphoma (4.1%). The most frequent unclassified type of uveitis was suspected sarcoidosis (22.3%). Analysis of the changes in the patterns of uveitis in the central Tokyo area from 2004 to 2012 to 2013-2015 revealed notable increasing trends of herpetic iridocyclitis and intraocular lymphoma, and increasing trends of bacterial endophthalmitis, fungal endophthalmitis, and juvenile chronic iridocyclitis. In contrast, the frequency of sarcoidosis, Behçet's disease, and Vogt-Koyanagi-Harada disease decreased. CONCLUSIONS: The patterns of uveitis changed considerably from 2004 to 2012 to 2013-2015. Continuous investigations about the epidemiology of uveitis are needed to diagnose uveitis more accurately.

Association between the functional PTPN22 G788A (R263Q) polymorphism and susceptibility to autoimmune diseases: A meta-analysis.

This study explored whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) G788A (R263Q) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted using 23 comparative studies with a total of 16,719 patients and 17,783 controls. The meta-analysis showed an association between the A allele of the PTPN22 G788A polymorphism and decreased risk of autoimmune diseases in all subjects (p < 0.001). Analysis after stratification by ethnicity indicated that the PTPN22 788A allele was significantly associated with autoimmune diseases in Europeans (p < 0.001) but not in Latin Americans. Meta-analysis by autoimmune disease type showed a significant negative association between the PTPN22 788A allele and systemic lupus erythematous (SLE) (p = 001), rheumatoid arthritis (RA) (p = 0.008), ulcerative colitis (UC) (p = 0.016), but not Crohn's disease (CD). A single study for each showed no association between the PTPN22 788A allele and systemic sclerosis, giant cell arteritis, Henoch-schonlein purpura, uveitis, and Grave's disease. This meta-analysis demonstrates that the PTPN22 G788A polymorphism confers protection against SLE, RA, and UC, supporting evidence of association of the PTPN22 gene with a subgroup of autoimmune diseases.

Turning a blind eye: HTLV-1-associated uveitis in Indigenous adults from Central Australia.

PURPOSE: We describe the first two cases of HTLV-1 associated uveitis to be associated with HTLV-1c subtype infection. METHODS: Case report. RESULTS: Uveitis was demonstrated in two Indigenous Australian men, both of whom had high HTLV-1c proviral loads in peripheral blood. Visual outcomes were poor in each case. CONCLUSION: Clinicians should be aware of HTLV-1c infection as a cause of uveitis in Australia, and HTLV-1 serology should be included in the basic uveitis work-up in HTLV-1-endemic areas.

Visual Prognosis and Associated Factors of Phacoemulsification and Intraocular Lens Implantation in Different Uveitis Entities in Han Chinese.

PURPOSE: To address the visual prognosis and associated predictors of phacoemulsification and intraocular lens implantation in different uveitis entities in Han Chinese. METHODS: A retrospective review of the uveitis patients who underwent phacoemulsification and intraocular lens implantation in our center between 2004 and 2014. RESULTS: The 158 patients (226 eyes) included anterior uveitis (45 eyes), posterior/pan-uveitis (61 eyes), Vogt-Koyanagi-Harada disease (79 eyes) and Behçet disease (41 eyes). At 6 months after surgery, best-corrected visual acuity (BCVA) significantly improved (p < 0.001) in all uveitis groups with 134 (59.3%) eyes achieving 20/40 or better. The anterior uveitis and Behçet disease groups had significantly better and worse visual outcomes than other groups, respectively. Poor preoperative BCVA, macular lesions, and secondary glaucoma were independent variables that predicted a poor visual outcome. CONCLUSIONS: Our current study revealed a generally favorable outcome and associated predictors of phacoemulsification and intraocular lens implantation in uveitic cataracts in Han Chinese.

Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan.

PURPOSE: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population. METHODS: A retrospective review of the past 80 years of reports from Hokkaido University Hospital. RESULTS: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet disease. Although Behçet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis. CONCLUSIONS: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.

The Pattern of Uveitis among Chinese, Malays, and Indians in Singapore.

PURPOSE: To describe the pattern of uveitis among Chinese, Malays, and Indians at a tertiary referral institution in Singapore. METHODS: Charts between January 1997 and December 2010 were retrospectively reviewed. Charts between January 2014 and December 2014 were prospectively reviewed. RESULTS: A total of 1249 and 148 charts were retrospectively and prospectively reviewed, respectively. The top causes of anterior uveitis (AU) were HLA-B27, idiopathic, and CMV AU. The top known causes of intermediate uveitis were tuberculosis, primary intraocular lymphoma, and sarcoidosis. The top causes of posterior uveitis were CMV retinitis, toxoplasmosis, and dengue maculopathy. The top causes of panuveitis were VKH, idiopathic panuveitis, tuberculosis, and Behçet disease. HLA-B27 and CMV AU were more frequent among Chinese (21% vs 9% (non-Chinese); p<0.001; 10% vs 5% (non-Chinese); p<0.001, respectively). Tuberculous uveitis was more frequent among Malays and Indians (12% (non-Chinese) vs 5% (Chinese), p<0.001). CONCLUSIONS: Different uveitis patterns were encountered among patients of different races.

Uveitis in Chinese Patients with Psoriasis.

PURPOSE: To investigate the clinical features of 51 uveitis patients with psoriasis in China. METHODS: The psoriasis type, demographics, ocular findings, auxiliary examination findings, complications, and therapeutic effects were analyzed. RESULTS: A total of 37 male and 14 female uveitis patients with psoriasis were classified into four groups: psoriasis vulgaris (29 cases); psoriatic arthritis (15 cases); psoriatic erythroderma (6 cases); and pustular psoriasis (1 case). The onset age of psoriasis was younger than for uveitis (p < 0.001). Anterior uveitis, panuveitis, and posterior uveitis was observed in 58.8%, 35.3%, and 5.9% of the patients, respectively. Hypopyon was more frequently noted in the group with psoriatic arthritis (p = 0.007). Optic disc staining was more frequently noted in the group with psoriatic erythroderma (p = 0.029). Significant visual improvement was observed in 17 patients. CONCLUSIONS: Uveitis can be associated with various types of psoriasis in China, but was most frequently observed in patients with psoriasis vulgaris and psoriatic arthritis.

Racial Influences of Uveitic Glaucoma: Consolidation of Current Knowledge of Diagnosis and Treatment.

INTRODUCTION: The etiology, frequency, manifestation, and treatment of uveitis and uveitic glaucoma are commonly influenced by race. MATERIALS AND METHODS: This study aims to review the effect of race on the diagnosis and treatment of patients with common diseases of uveitis that may develop into glaucoma. RESULTS: Race affects the presentation and prevalence of uveitis. Sarcoidosis, for example, is more common in Blacks than in Whites in the United States. Furthermore, Blacks more commonly have anterior segment involvement, while Whites more commonly have posterior segment involvement. In addition, treatments-such as steroid implants and trabeculectomy-in the setting of uveitis and uveitic glaucoma may have higher risk of failure in Black patients. DISCUSSION: Over the last half-century, we have increased our understanding of the role of race in uveitis and uveitic glaucoma. Major gaps remain and further study is needed.

Clinical Characteristics of Inflammatory Choroidal Neovascularization in a Chinese Population.

PURPOSE: To describe demographic features and clinical and imaging characteristics of inflammatory choroidal neovascularization (CNV) in a Chinese population. METHODS: A retrospective case review of patients with CNV secondary to uveitis from 2002 to 2013. RESULTS: A total of 125 patients (150 eyes, 166 CNVs; bifocal CNVs in 16 eyes), 64% of whom were women, were reviewed. The mean age was 35.86 years. The proportions of patients with punctate inner choroidopathy (PIC), multifocal choroiditis (MFC), and Vogt-Koyanagi-Harada (VKH) were 50.4, 22.4, and 8%. All of the cases were classic CNV in fluorocein angiography and type 2 CNV in OCT. The proportion of subfoveal lesions in active CNV (30.09%) was less than that in inactive CNV (60.38%). CONCLUSIONS: PIC, MFC, and VKH were the three primary specific types of uveitis with inflammatory CNV in this study. Inflammatory CNV tended to break though the retinal pigment epithelium and beneath the neurosensory retina. Moreover, inflammatory CNV was usually nonsubfoveal when it occurred.

The Association of Race With Childhood Uveitis.

PURPOSE: To identify risk factors for a severe uveitis course among children with noninfectious uveitis. DESIGN: Retrospective cohort study. METHOD: This was a retrospective analysis of a prospectively collected database. Records of 94 children with uveitis were reviewed at enrollment and every 3-6 months (2011-2015). Severe uveitis was defined as a history of ocular complications or a visual acuity (VA) of ≤20/200. Children were compared by disease, VA, complications, and race. Regression models were used to model risk factors for severe disease. When examining race, we focused on non-Hispanic African-American and non-Hispanic white children only. RESULTS: Of 85 children with uveitis and complete ocular examinations, 27 (32%) had a history of a VA of ≤20/200. A subanalysis of non-Hispanic African-American and white children showed an increased prevalence of VA ≤20/200 in non-Hispanic African-Americans (18/25; 72% vs 4/43; 9%). Non-Hispanic African-Americans were more likely to be diagnosed at an older age (P = .030) and to have intermediate uveitis (P = .026), bilateral disease (P = .032), a history of VA ≤20/50 (P = .002), VA ≤20/200 (P < .001), and a higher rate of complications (P < .001). On multivariable analysis, non-Hispanic African-American race was a significant predictor of blindness (OR = 31.6, 95% CI 5.9-168.5, P < .001), after controlling for uveitis duration. Non-Hispanic African-Americans also developed 2.2 times more unique complications per year of disease than non-Hispanic whites when controlling for uveitis type and duration. CONCLUSIONS: There appear to be racial differences in the outcomes of children with uveitis. Non-Hispanic African-American children with non-juvenile idiopathic arthritis-associated uveitis may have worse visual outcomes with increased vision loss and ocular complications. These findings highlight the need for future studies in minority populations.

Characteristics of a cohort of children with Juvenile Idiopathic Arthritis and JIA-associated Uveitis.

BACKGROUND: Juvenile idiopathic arthritis-associated uveitis (JIA-U) can lead to poor visual outcomes and impact a child's quality of life (QOL) and function. Our aim is to identify risk markers of JIA-U and examine differences in the QOL of children with JIA and JIA-U. METHODS: Rheumatology and ophthalmology record reviews and questionnaires were completed every 4-6 months on 287 children with JIA. We collected arthritis, uveitis, and QOL data. We examined data through last study visit. RESULTS: There were 52/287 (18%) children with JIA-U who were younger at arthritis diagnosis, had oligoarticular persistent JIA, and ANA positive. Confirmed uveitis predictors were age at JIA diagnosis (OR = 0.86) and oligoarticular subtype (OR = 5.92). They had worse vision specific QOL and function, but similar general QOL. Blindness occurred in 17.5% of children but was more common in African American children compared to non-Hispanic Caucasian children ((5/7 (71%) vs. 2/29 (7%), p <0.001) despite a similar uveitis prevalence (22% vs. 16%). Both races had similar complications, although band keratopathy was more frequent in African Americans (75% vs. 15.6%, p = 0.003). CONCLUSIONS: We confirm young age at JIA diagnosis and the oligoarticular JIA subtype as predictors of uveitis development. Although we were unable to identify predictors of ocular complications or blindness, AA children appeared to have a more severe disease course manifested by increased ocular complications, vision loss and blindness. Potential causes that warrant additional study include underlying disease severity, access to medical care and referral bias. Further investigation of the risk factors for vision-compromising uveitis and its' long-term effects should be conducted in a large racially diverse population.

A report of an adult case of tubulointerstitial nephritis and uveitis (TINU) syndrome, with a review of 102 Japanese cases.

BACKGROUND: Although TINU syndrome is characterized by idiopathic TIN with bilateral anterior uveitis, few reports have provided a comprehensive summary of the features of this disorder. Previous reports have suggested that many Japanese patients had HLA-A2 and -A24 (7), but there is no evidence. CASE REPORT: A 44-year-old female was referred to our hospital due to renal dysfunction in March 2012. After admission, her symptoms improved spontaneously without medication within 2 weeks. In the outpatient clinic, she was diagnosed with idiopathic bilateral anterior uveitis in May, and her renal dysfunction relapsed in November. A renal biopsy showed diffuse TIN. We made a diagnosis of TINU syndrome because we could not explain the origin, and treated her with a systemic corticosteroid. Her renal function and ocular symptoms have been improving. The patient had HLA-A24, -B7, -DR1, -C*07: 02 and -DQB1*05: 01: 01. We collected 102 Japanese cases in PubMed, Ovid MEDLINE, and the Japanese Medical Abstracts Society and compared our case with the previous cases. CONCLUSIONS: This disorder affects primarily young females (median age, 14 years), and the most common symptom is fever (44/102 cases). We conducted a statistical analysis using contingency table and Pearson's chi-square test, for HLA-A2 and A24, and calculated the odds ratio (OR). There are no significant differences (A2 was present in 7/22 cases and in 19/50 controls, p value (P) 0.61, OR 0.76 (95% confidence interval (CI)) 0.27-2.2; A24 was present in 10/22 cases and in 33/50 controls, P 0.10, OR 0.43, CI 0.16-1.2).

Association Between Copy Number Variations of TLR7 and Ocular Behçet's Disease in a Chinese Han Population.

PURPOSE: The purpose of this study was to test whether gene copy number variations (CNVs) of Toll-like receptors (TLRs) are associated with uveitis. METHODS: Copy number variations of TLRs were detected by real-time PCR. The first stage of the study consisted of enrolling 400 Behçet's disease (BD) patients, 400 Vogt-Koyanagi-Harada syndrome patients, 400 patients with acute anterior uveitis associated with or without ankylosing spondylitis, and 600 healthy subjects. The second stage included another set of 578 BD patients and 1000 healthy controls. The frequencies of TLR gene copy number types (TLR1, TLR2, TLR3, TLR5, TLR6, TLR7, TLR9, TLR10) were compared among patients and controls by using the χ(2) test. Real-time PCR was used to detect mRNA expression from peripheral blood mononuclear cells (PBMCs) obtained from healthy controls following stimulation with the TLR7 agonist R848. Levels of TNF-α, IL-6, IL-1ß, and IFN-ß in culture supernatants were measured by ELISA. RESULTS: All TLRs tested, except for TLR7, had a gene copy number of two in more than 98% of individuals tested. In the first stage, we found a significantly increased frequency of more than one copy of TLR7 (located on the X chromosome) in male BD patients and more than two copies in female patients (correction of P value [PC] = 0.021; PC = 0.048, respectively). A second stage and combined study confirmed the association (PC = 1.14 × 10(-6); PC = 9.12 × 10(-5), respectively). TLR7 mRNA expression in PBMCs was increased in healthy male carriers having more than one copy of TLR7 or females having more than two copies following stimulation with R848 (P = 0.021, P = 0.006, respectively). No effect of the various TLR7 copies on the release of TNF-α, IL-6, IL-1ß, and IFN-ß could be detected. CONCLUSIONS: This study provides evidence that a high copy number of TLR7 confers risk for BD in a Chinese Han population. (http://www.chictr.org number, ChiCTR-CCC-12002184.).