Clinical Features And Cytokine Expression Profiles In Aqueous Humor And Sera Of Patients With HLA-B27 Positive And Idiopathic Anterior Uveitis

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.