【作者】 陈暐；

【导师】 陈玲；

【作者基本信息】 复旦大学 ， 眼科学， 2013， 硕士

【摘要】 目的观察HLA-B27阳性和HLA-B27阴性特发性急性前葡萄膜炎患者的临床特征表现以及预后,并通过检测两组患者炎症活动期房水及血清中致炎性Th1、Th17相关细胞因子的表达程度,探讨不同类型的葡萄膜炎的临床表现及可能存在的发病机制。方法1.收集2012年8月至2013年3月在本院诊断急性前葡萄膜炎(acute anterior uveitis, AAU)患者20例,记录基本资料。按照外周血清人类白细胞抗原(human leukocyte antigen, HLA)-B27表达与否,和入组标准分为9例HLA-B27阴性特发性急性葡萄膜炎患者(组I)及11例HLA-27阳性急性葡萄膜患者(组II),其中HLA-B27阳性AAU患者在再分为6例伴有全身系统性疾病者(组IIA)及5例不伴有全身系统性疾病者(组IIB)。用SPSS 17.0软件进行数据分析,比较组1和组II、组IIA和组IIB患者的临床特征及预后之间是否存在统计学差异。2.同期收集17例孔源性视网膜脱离患者作为健康对照。采集HLA-B27阴性特发性AAU、HLA-B27日性AAU和对照组的的房水及血清,利用免疫磁珠技术检测各组房水及血清中IL-1β、IL-4、IL-6、IL-10、IL-17A、 IL-17F、1L-21、IL-22、IL-23、IL-25、IL-31、IL-33、IFN-γ、TNF-α和sCD40L等细胞因子的含量。用SPSS17.0软件进行统计学分析两种葡萄膜炎中各类细胞因子在炎症活动期的表达情况,与炎症严重程度的相互关系,探讨不同葡萄膜炎的可能发病机制。结果1. HLA-B27阳性AAU患者的疾病复发率(P=0.006)、单眼交替发病比例(P=0.002)及出现前房积脓人数比例(p=0.031)显著高于HLA-B27阴性特发性AAU患者,且HLA-B27阳性AAU中以男性患者居多,具有统计学意义(P=0.006)；在并发症及视力及视力预后方面,两组患者之间无明显统计学差别。伴或不伴有全身系统性疾病HLA-B27阳性AAU的患者,其各个观察指标及预后无显著差异。2.总体AAU患房水中,除IL-21、IL-22、IFN-γ (P> 0.05)和IL-23(P=0.000)之外,其余细胞因子浓度均显著高于对照组,且AAU患者房水内多种细胞因子浓度均高于血清浓度,除IL-21、IL-22、IFN-γ(P> 0.05)和IL-23(P=0.003)之外。各类细胞因子在AAU患者血清内的浓度与对照组相比均无统计学意义(均为P>0.05)。各类细胞因子在HLA-B27阴性与HLA-B27阳性组的房水和血清中表达无统计学差异(均为P>0.05)。统计显示,HLA-B27阳性组的炎症活动度与房水IFN-γ呈正相关(r=0.668,P=0.025)；而HLA-B27阴性特发性组的炎症活动度与房水1L-17A、IL-17F(r=0.756, P=0.019; r=0.702, P=0.035)呈正相关。各类细胞因子在房水中的表达基本与炎症表现相符。结论1.尽管HLA-B27阳性AAU患者的前房炎症反应较重,且伴有较高的复发率,但HLA-B27阳性AAU和HLA-B27阴性特发性AAU患者的临床表现相近,并均有较好的视力改善及预后。2.不同的葡萄膜炎均可由Th17免疫效应引起,但Th17并非为单一的致病机制。HLA-B27阳性AAU可能由Thl以及Th17共同作用的导致的免疫性疾病,且以Thl起到主导作用。而HLA-B27阴性特发性AAU更加倾向以IL-17效应(Th17)为主导的免疫性疾病。更多还原

【Abstract】 ObjectiveClinical features and prognosis of HLA-B27 positive acute anterior uveitis (AAU) were assayed compared with HLA-B27 negative idiopathic AAU, and to study the immunopathogenic mechanism of both disease group by determining the cytokines expression profile in aqueous humor (AqH) and sera.Methods1.20 patients diagnosed with AAU in outpatient ward of ENT Hospital of Fudan University from August 2012 to March 2013 were recruited in the study. Ocular examinatfon was performed on each patient and general informatfon was documented. Study subjects included 9 HLA-B27 negative, idiopathic AAU patients (group I) and 11 HLA-B27 positive AAU patients (group Ⅱ), based on the present of human leukocyte antigen B27 and selection criteria. HLA-B27 positive group was further divided into 6 with associated systemic (group IIA) and 5 without associated systemic disease (group ⅡB). The difference in clinical features and prognosis of group Ⅰ and Ⅱ, group ⅡA and IIB were evaluated using SPSS 17.0 statistical analysis.2.17 patients with rhegmatogenous retinal detachment (RRD) were served as control specimens. AqH and sera were collected from patients with AAU and controls. The concentration of 15 immune mediators (IL-1β、IL-4、IL-6、 IL-10、IL-17A、IL-17F、IL-21、IL-22、IL-23、IL-25、IL-31、IL-33、IFN-γ、 TNF-α and sCD40L) were measured in both AqH and sera simultaneously by multiplex immunoassay. Independent t-test was used where appropriate for the determination of statistical significance. Spearman’s correlation coefficients were conducted to investigate the correlations between variables. SPSS version 17.0 was used, and the results were considered to be significant at P values of less than 0.05.Results1. Significantly more server anterior chamber inflammation in term of hypopyon formation (P=0.031) was observed with higher frequency (P=0.006) of anterior uveitis attacks in the HLA-B27 positive group than in the HLA-B27 negative group. In addition, there is a significant male preponderance (P=0.006) in HLA-B27 positive group. However, no significant differences were observed for final ocular and visual outcome between theses two group. Associated systemic diseases showed no statistical significance in the clinical manifestation and prognosis in the HLA-B27 positive AAU patients.2. The levels of multiple cytokines in all aqueous humor samples were significantly higher from patients with uveitis than control patients, expect IL-21, IL-22, IFN-y (P>0.05) and IL-23 (P=0.001), furthermore, the concentration of multiple cytokines in aqueous humor from patients with uveitis was higher than theses in serum, expect IL-21, IL-22, IFN-γ (P>0.05) and IL-23 (P=0.003); the levels of cytokines in serum from patients with AAU showed no significant difference with those in serum from controls (P>0.05); besides, no remarkable difference in the cytokines expression pattern in aqueous humor and serum between HLA-B27 positive group and HLA-B27 negative group (P>0.05); the level of IL-17A and IL-17F in aqueous humor sample correlated significantly with disease activity in patient with HLA-B27 negative, idiopathic AAU (r=0.756, P=0.019 and r=0.702, P=0.035, respectively); whereas the level IFN-y in aqueous humor correlated significantly with disease activity in patients with HLA-B27 positive AAU(r=0.668, P=0.025). The expression of cytokines in aqueous humor was consistent with the process of ocular inflammation.Conclusion1. Despites more server inflammation and higher recurrence rate, data suggested that both HLA-B27 positive and negative, idiopathic AAU patients have similar clinical features, and showed similar good final ocular and visual outcomes.2. These data suggested that T helper (Th) 17 cells were implicated in the immunopatho genes is of both uveitis, as elevated levels of Th17-associated cytokines were detected in the aqueous humor from these AAU patients. However, the condition of disease induction could attribute with other mechanism. HLA-B27 positive AAU is characterized by Thl and Thl7-driven immune responses, and Thl-type immune responses are more potent, in contrast, more extensive Th17-type immune responses is suggested in patients with HLA-B27 negative, idiopathic AAU.更多还原