Study On The Clinical Characteristics Of Behcet 's Disease Uveitis And The Candidate Gene Of Behcet' S Disease

Part One Clinical Features of 132 Patients with Behcet’s UveitisPurpose:To characterize the clinical features of patients with Behcet’s uveitis.Methods:Medical records of patients who were diagnosed as Behcet’s uveitis in Peking Union Medical College Hospital between 1998 and 2015 were retrospectively reviewed. Questionnaires were applied for additional information.Results:A total of 132 patients (233 eyes) with Behcet’s uveitis were included, among which 104 (78.8%) were male and 28 (21.2%) were female. The average age at the onset of uveitis was (28.9 + 8.7) years, mainly concentrated on (21-40) years (77.3%). Ocular involvement was bilateral in 76.5% patients and panuveitis was the most common type (83.3%). Complications were seen in 80.7% eyes, with cataract (59.1%) and macular edema (59.1%) were the most common anterior and posterior segment complication, respectively. Patients’ visual acuity was impaired:at the 5th year of uveitis,44% eyes with a best corrected visual acuity of log MAR 1.0 or worse. Fluorescein fundus angiography is an important auxiliary examination for detect and evaluate the inflammation of the fundus. Oral aphthae (100.0%) was the most frequent extraocular manifestation, followed by dermatologic lesions (78.0%), genital ulcers (68.2%), arthritis (33.3%) and positive pathergy test (29.5%). A combination of glucocorticoid and immune modulators remained the first line treatment (96.9%) for Behcet’s uveitis, for refractory cases, an addition of biological agents provided better effect.Conclusion:Behcet’s uveitis mainly affects working-age male and manifest as bilateral panuveitis. Complications are commonly seen in uveitis eyes. Patients’ visual acuity is badly impaired. A combination of glucocorticoid and immune modulators is effective for most patients, but for refractory cases, an addition of biological agents provides better effect.Part Two Comparison of Visual Prognosis of Cataract Surgery between Behcet’s Uveitis and Other Uveitis Entities in Han Chinese and Analysis of Associated Factors for Poor Visual OutcomePurpose:To compare the visual prognosis of phacoemulsification and intraocular lens implantation between Behcet’s uveitis and other uveitis entities in Han Chinese and analyze associated predictors for poor visual outcome.Methods:Retrospective review of the uveitis patients who underwent phacoemulsification and intraocular lens implantation in Peking Union Medical College Hospital between July 2004 and October 2014.Results:A total of 158 patients (273 eyes) were included, with Behcet’s uveitis in 28 patients (41 eyes), Vogt-Koyanagi-Harada disease (VKH) in 42 patients (79 eyes), anterior uveitis in 37 patients (45 eyes) and posterior/pan-uveitis in 49 patients (61 eyes). At 6 months after surgery, best-corrected visual acuity significantly improved (P<0.001) in all uveitis groups with 134 (59.3%) eyes achieved 20/40 or better, the Behcet’s uveitis group with only 5 (12.2%) eyes achieved 20/40 or better had significantly worse visual outcomes than any other group (Pc<0.001). Poor preoperative best-corrected visual acuity, macular lesions and secondary glaucoma were independent variables that predicted a poor visual outcome. The Behcet’s uveitis group got the worst preoperative best-corrected visual acuity (Pc<0.05) and the most macular lesions (Pc<0.001) compared with any other group.Conclusions:Our current study revealed a generally favorable outcome and associated predictors of phacoemulsification and intraocular lens implantation in uveitic cataracts in Han Chinese. Compare with other group, Behcet’s uveitis group had worse visual outcome than other groups.Part Three Candidate Genes Association Study of Behcet’s Disease in Chinese Han PopulationPurpose:FUT2 and IL33/IL1RL1 gene polymorphisms were described to be associated with Behcet’s disease and other autoimmune disease in Caucasian population, respectively. This study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) in the FUT2 region (rs418821, rs16982241 and rs281377) and IL33/IL1RL1 region (rs11792633, rs7025417, rs10975519, rs1048274/rs2310220, rs12712142, rs13424006, rs3821204) with Behcet’s disease in Chinese Han population.In addition, we determine whether SNPS in the above there gene and rs9266409 in HLA-B gene (the well-known BD associated gene) show any genetically predisposition to patients with ocular involvement.Methods:A total of twelve SNPs in the four candidate genes were genotyped in a cohort of 783 Behcet’s disease patients (398 with ocular involvement and 385 without) and 701 healthy controls, by using the Matrix Assisted Laser Desorption/ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). The alleles, genotypes, and haplotypes of the SNPs were analyzed with PLINK1.07 or Haploview 4.0.Results:Associations were observed between rs12712142 in IL1RL1 region and Behcet’s patients, and between rs281377 in FUT2 region and Behcet’s patients without ocular involvement when directly analyzed or analyzed under genetic models (all P<0.05). Genetic variant of rs9266409 in HLA-B gene was more commonly seen in Behcet’s patients with ocular involvement (P>0.05). The frequencies of alleles, genotypes and haplotypes of SNPs in FUT2 (rs418821 and rs16982241), IL-33 (rs7025417, rs11792633, rs10975519 and rs1048274) and IL1RL1 (rs2310220 and rs13424006) were not significantly different between the Behcet’s patients and controls (all P>0.05). rs3821204 in the IL1RL1 region was excluded from subsequent analysis for it deviated from Hardy—Weinberg genetic equilibrium in the control group.Conclusions:Our study reveals that FUT2 gene polymorphism is associated with Becet’s disease without ocular involvement, IL1RL1 is associated with Behcet’s disease and genetic variant in HLA-B is more common in patient with ocular involvement in Chinese Han population, indicating the participation of the above genes in Bechet’s disease and a different role in patients with or without ocular involvement.