Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling.

Dendritic cells (DCs) are the major antigen-presenting cells and play an important role in autoimmune uveitis. Emerging evidence suggests that bile acids (BAs) regulate DCs maturation. However, the underlying mechanisms by which BAs regulate the function of DCs still need to be clarified. Here, we demonstrate that lithocholic acid (LCA) inhibits the production of pro-inflammatory cytokines and the expression of surface molecules in bone marrow-derived dendritic cells (BMDCs). LCA attenuates the severity of EAU by modulating the maturation of splenic CD11C+MHCIIhigh DCs. Notably, Takeda G-protein coupled receptor 5 (TGR5) deficiency partially reverses the inhibitory effect of LCA on DCs in vitro and in vivo. TGR5 activation also downregulates the NF-κB and MAPK pathways by inhibiting glutathione production and inducing oxidative stress in DCs, which leads to apoptosis and autophagy in DCs. In addition, LCA or INT-777 treatment increases the TGR5 expression in monocyte-derived dendritic cells (MD-DCs) of patients with active BD, whereas both LCA and TGR5 agonists inhibit the activation of MD-DCs. These results suggest that LCA and TGR5 agonists might be potential therapeutic drugs for the treatment of autoimmune uveitis.

Progranulin Suppressed Autoimmune Uveitis and Autoimmune Neuroinflammation by Inhibiting Th1/Th17 Cells and Promoting Treg Cells and M2 Macrophages.

BACKGROUND AND OBJECTIVES: Progranulin (PGRN) is an important immune regulatory molecule in several immune-mediated diseases. The objective of this study is to investigate the role of PGRN in uveitis and its counterpart, experimental autoimmune uveitis (EAU), and experimental autoimmune encephalomyelitis (EAE). METHODS: Serum PGRN levels in patients with Behcet disease (BD) or Vogt-Koyanagi-Harada (VKH) disease and normal controls were measured by ELISA. EAE and EAU were induced in B10RIII, wild-type, and PGRN-/- mice to evaluate the effect of PGRN on the development of these 2 immune-mediated disease models. The local and systemic immunologic alterations were detected by ELISA, flow cytometry, and real-time PCR. RNA sequencing was performed to identify the hub genes and key signaling pathway. RESULTS: A significantly decreased PGRN expression was observed in patients with active BD and active VKH. Recombinant PGRN significantly reduced EAU severity in association with a decreased frequency of Th17 and Th1 cells. PGRN-/- mice developed an exacerbated EAU and EAE in association with strikingly increased frequency of Th1 and Th17 cells and reduced frequency of regulatory T (Treg) cells. In vitro studies revealed that rPGRN could inhibit IRBP161-180-specific Th1 and Th17 cell response and promote Treg cell expansion. It promoted non-antigen-specific Treg cell polarization from naive CD4+ T cells in association with increased STAT5 phosphorylation. Using RAN sequencing, we identified 5 shared hub genes including Tnf, Il6, Il1b, Cxcl2, and Ccl2 and the most significantly enriched MAPK and tumor necrosis factor signaling pathway in PGRN-/- EAU mice. The aggravated EAE activity in PGRN-/- mice was associated with a skew from M2 to M1 macrophages. DISCUSSION: Our results collectively reveal an important protective role of PGRN in EAU and EAE. These studies suggest that PGRN could serve as an immunoregulatory target in the study of prevention and treatment for the Th1/Th17-mediated diseases.

Identification of Novel Risk Loci for Behçet's Disease-Related Uveitis in a Chinese Population in a Genome-Wide Association Study.

OBJECTIVE: To explore susceptibility loci associated with uveitis in Behçet's disease (BD). METHODS: We conducted a 2-stage study, consisting of a genome-wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD-related uveitis and 4,388 controls, and the replication stage included 953 cases with BD-related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1. RESULTS: Three independent HLA alleles (HLA-B51 [3.75 × 10-190 ], HLA-A26 [1.50 × 10-18 ], and HLA-C0704 [3.44 × 10-16 ]) were identified as having a genome-wide association with BD-related uveitis. In the non-HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1. CONCLUSION: This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.

Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling.

Gut microbiota-mediated secondary bile acids (BAs) play an important role in energy balance and host metabolism via G protein-coupled receptors and/or nuclear receptors. Emerging evidence suggests that BAs are important for maintaining innate immune responses via these receptors. However, the effect of BAs on autoimmune uveitis is still unknown. Here, we demonstrate decreased microbiota-related secondary BA concentration in feces and serum of animals with experimental autoimmune uveitis (EAU). Restoration of the gut BAs pool attenuates severity of EAU in association with inhibition of nuclear factor κB (NF-κB)-related pro-inflammatory cytokines in dendritic cells (DCs). TGR5 deficiency partially reverses the inhibitory effect of deoxycholic acid (DCA) on DCs. TGR5 signaling also inhibits NF-κB activation via the cyclic AMP (cAMP)-protein kinase A (PKA) pathway in DCs. Additionally, both DCA and TGR5 agonists inhibit human monocyte-derived DC activation. Taken together, our results suggest that BA metabolism plays an important role in adaptive immune responses and might be a therapeutic target in autoimmune uveitis.

Prevalence, risk factors and management of ocular hypertension or glaucoma in patients with Vogt-Koyanagi-Harada disease.

BACKGROUND/AIMS: This study was performed to examine the prevalence, risk factors and treatment outcome of OHT/glaucoma in Chinese patients with Vogt-Koyanagi-Harada (VKH). METHODS: Retrospective non-interventional case series were conducted on a total of 2281 patients with VKH referred from April 2008 to April 2019. Of these cases, 1457 had a minimum follow-up period of 3 months and were included for this study. Medical records were reviewed for demographic, ocular and treatment data. RESULTS: Among 2914 eyes of 1457 patients with VKH, 695 (23.9%) eyes of 425 patients (29.2%) developed OHT/glaucoma. The risk factors of OHT/glaucoma included initial BCVA of 20/200 or worse (OR=4.826), final best-corrected visual acuity (BCVA) of 20/50-20/100 (OR=5.341) and final BCVA of 20/200 or worse (OR=4.235), the interval between uveitis attack and referral time interval being 2 months or more (OR=3.318), more than three recurrent episodes (OR=4.177) and posterior synechiae (OR=1.785). The main possible mechanisms of OHT/glaucoma were inflammatory factor-induced open-angle OHT/glaucoma in 277 eyes (39.9%) and pupillary block arising from complete posterior synechiae in 201 eyes (28.9%). In these 695 eyes with OHT/glaucoma, normalised intraocular pressure (IOP) was achieved in 389 eyes (56.0%) following medical treatment. In the remaining 306 eyes, various surgical interventions were performed and a normalised IOP could be achieved in 249 eyes (81.4%). CONCLUSION: OHT/glaucoma is a common complication in Chinese patients with VKH. Risk factors of OHT/glaucoma included worse acuity at first and final visits, the longer interval between uveitis attack and referral, more recurrent episodes and posterior synechiae.

Expression and Genetic Polymorphisms of ERCC1 in Chinese Han Patients with Oral Squamous Cell Carcinoma.

The aim of this study was to investigate the expression of the excision repair cross-complementation group 1 (ERCC1) in oral squamous cell carcinoma (OSCC) and the possible association of ERCC1 polymorphisms with susceptibility and response to chemotherapy of OSCC in a Chinese Han population. The expression of ERCC1 was determined by real-time PCR in eight patients. Four single-nucleotide polymorphisms (SNPs) rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were genotyped in 113 OSCC patients and 184 healthy controls using a PCR restriction matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) assay. We found that a higher gene expression of ERCC1 was observed in tumor tissue as compared to pericarcinomatous tissue in OSCC patients. All genotypic and allelic frequencies of the tested ERCC1 polymorphisms were in Hardy-Weinberg equilibrium. The genotypic and allelic frequencies of rs11615, rs3212948, rs3212961, and rs735482 of ERCC1 were not different between OSCC patients and controls. No correlation was observed between ERCC1 polymorphisms and the response to chemotherapy. Our results show that ERCC1 is increased in the tumor tissue of OSCC patients. The investigated ERCC1 gene polymorphisms (rs11615, rs3212948, rs3212961, and rs735482) are not associated with the susceptibility and response to chemotherapy of OSCC in our investigated Chinese Han population.

Increased Expression of Indoleamine 2,3-Dioxygenase (IDO) in Vogt-Koyanagi-Harada (VKH) Disease May Lead to a Shift of T Cell Responses Toward a Treg Population.

Previous studies have pointed out that indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme initiating tryptophan metabolism, plays a role in the regulation of the immune system. This project was designed to investigate the potential role of IDO in monocyte-derived dendritic cells (moDCs) obtained from active Vogt-Koyanagi-Harada (VKH) disease patients. In this study, we found that the IDO mRNA expression and enzyme activity were increased in active VKH patients as compared with healthy controls and patients in remission. To investigate the role of IDO in immune regulation, an effective inhibitor 1-methyl-L-tryptophan (1-MT) was used to suppress its activity in DCs. The results showed that inhibition of IDO with 1-MT significantly decreased the expression of DC marker CD86. IDO inhibition did not affect the cytokine production of IL-6, IL-1ß, TNF-α, IL-10, and TGF-ß in DCs. Downregulation of IDO in DCs also led to the reduction of regulatory T (Treg) cells and an increased CD4+ T cell proliferation. Treatment with 1-MT did not affect the phosphorylation of the MAPK pathway in DCs. In general, our study suggests that IDO may play an important role in the pathogenesis of VKH disease by regulating DC and CD4+ T cell function. Tryptophan deficiency and kynurenine accumulation may account for the complicated effects of IDO. Further research is needed to study the precise tryptophan metabolites that may limit immune responses in VKH disease.

Long non-coding RNA TP73-AS1 promotes TFAP2B-mediated proliferation, metastasis and invasion in retinoblastoma via decoying of miRNA-874-3p.

Retinoblastoma (RB) is one of the most common ophthalmic tumors, and most of the patients have been identified as advanced at the time of diagnosis, which is directly related to high mortality. Recent studies showed that long noncoding RNA (lncRNA) and miRNAs play key roles in the development、progression、or treatment of cancer, such as RB. However, the role of lncRNA -TP73-AS1 in RB remains unclear. In this study, we performed functional and mechanistic investigation of miRNA-874-3p-TP73-AS1 interaction in RB. The experiments results revealed that miRNA-874-3p had anti-oncogenic functions in RB. Moreover, the bioinformatics analysis shown that TP73-AS1 could bind to miRNA-874-3p. TP73-AS1 was inversely correlated with miRNA-874-3p expression. Furthermore, studies confirmed that TP73-AS1 negatively regulated miRNA-874-3p expression via functioning as a ceRNA. In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis. Graphical abstract.

A20 Inhibits Intraocular Inflammation in Mice by Regulating the Function of CD4+T Cells and RPE Cells.

A20 is a negative regulator of inflammation and immunity and plays a role in several autoimmune and inflammatory diseases. Here, we demonstrate that A20 overexpression significantly ameliorates severity of EAU by inhibiting the infiltration of Th1 and Th17 cells, and by protecting integrity of the blood retinal barrier. In vitro studies showed that A20 silencing could promote CD4+T cells toward a Th1 and Th17 phenotype. A decreased expression of A20 in CD4+T cells was noticed in active BD patients but not in VKH patients. Furthermore, silencing of A20 in hRPE cells induced the production of IL-6, IL-8, and MCP-1 and downregulated ZO-1 and occludin expression which is mediated by inhibition of MAPK and NF-κB pathways. This study reveals a mechanism by which A20 prevents autoimmune uveitis.

Macular Abnormalities in Vogt-Koyanagi-Harada Disease.

Purpose: To investigate the prevalence of macular abnormalities in Chinese Vogt-Koyanagi-Harada (VKH) patients.Methods: Clinical characteristics, therapeutic effectiveness and visual outcome were reviewed and analyzed.Results: The most common macular abnormality was macular edema (ME), followed by macular choroidal neovascularization (CNV). Macular abnormalities were associated with recurrent episodes, disease course and visual acuity ≤20/50 at first visit. The prevalence of macular abnormalities in patients who were not treated according to our regular treatment regimen with corticosteroids combined with immunosuppressive agents and who were followed-up for at least one year (13.1%) was significantly higher than in patients receiving the regular treatment (5.7%). Visual improvement was found in 66.7% of eyes with macular abnormalities after regular treatment.Conclusion: Macular abnormalities were associated with recurrent uveitis, course of disease and lower visual acuity at first visit. Regular treatment could prevent the development of macular abnormalities and improved visual outcome in most patients.

Long-Term Efficacy and Safety of Interferon Alpha-2a in the Treatment of Chinese Patients with Behçet's Uveitis Not Responding to Conventional Therapy.

PURPOSE: To investigate the long-term efficacy and safety of interferon alpha-2a (IFNα-2a) in Chinese patients with Behçet's uveitis (BU) refractory to conventional therapy. METHODS: In a prospective observational cohort study, 127 patients were treated with an initial dosage of 3 million units per day in the first three months, followed by gradual tapering of the dose. RESULTS: After 3 months of treatment, IFNα-2a was shown to be effective in 115 cases (91%). At the end of the 1-year follow-up, the frequency of ocular relapses decreased to 1.59 ± 1.68 per year (ranging 0-6) (p < 0.001), as compared to 5.09 ± 2.51 per year (ranging 3-15). Moreover, the frequency of oral ulcer relapses also decreased to 2.49 ± 1.84 per year (ranging 0-6) (p < 0.001), as compared to 8.20 ± 3.72 per year (ranging 2-10). Visual improvement or stability was observed in 32 patients (59%) in these 54 patients. During a mean follow-up of 11 months (range 3-33), the mean final VA (logMAR) had progressed from 1.0 logMAR to 0.8 logMAR in all treated patients. CONCLUSIONS: Long-term low dose of IFNα-2a is useful in treating Chinese BU patients who do not respond adequately to conventional therapy.

Decreased interleukin(IL)-35 Expression is Associated with Active Intraocular Inflammation in Vogt-Koyanagi-Harada (VKH) Disease.

Purpose: Recent studies have reported that IL-35 has a protective effect in autoimmune disease. In this study, we explored the role of IL-35 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Methods: The IL-35/EBI3 and IL-35/P35 mRNA level was assayed by Real-Time PCR. The level of IL-35 in serum was detected by ELISA. PBMCs and monocyte-derived DCs were cultured with or without IL-35 and the concentration of IL-17, IL-10, IFN-γ, IL-6, TNF-α, and IL-1ß in supernatants was tested by ELISA. Results: The serum level of IL-35 is reduced in active VKH patients. The mRNA expression of the two subunits IL-35/EBI3 and IL-35/P35 in PBMCs from patients with active VKH was also decreased. IL-35 significantly inhibited IFN-γ and IL-17 expression and induced IL-10 production by PBMCs and inhibited IL-6 production by monocyte-derived DCs. Conclusion: The current study suggests that a decreased IL-35 expression may be involved in the pathogenesis of VKH disease.

Clinical features of Chinese patients with relapsing polychondritis.

PURPOSE: To characterise the ocular and extraocular findings in patients with relapsing polychondritis (RP) patients. DESIGN: Retrospective, longitudinal study. METHODS: A total number of 16 patients with ocular RP, seen in our tertiary uveitis referral centre over a time period of 10 years were included in this study. Routine ocular examinations such as best-corrected visual acuity, intraocular pressure, slit-lamp biomicroscopy, ophthalmoscopy and auxiliary examinations including ultrasound biomicroscopy, B-scanultrasonography, fundus fluorescein angiography and optical coherence tomography were performed. Ocular and systemic manifestations of these 16 patients were analysed and compared with those presented by others. The patients were treated by corticosteroids or in combination with immunosuppressive agents. RESULTS: Eleven male and five female patients were included with a mean age of 40.4 years. Ocular involvement was bilateral in 75% of the patients and manifested as scleritis (n=10) or uveitis (n=6). Generalised, anterior and posterior uveitis was found in three, two and one patients, respectively. The frequencies of inner ear involvement and arthritis were lower in Chinese patients compared with that observed in Caucasians. Nine patients had a follow-up of 2-44 months, and in these individuals a better visual prognosis was observed in female patients compared with males. CONCLUSIONS: Our study shows that uveitis associated with RP may manifest as generalised, anterior or posterior uveitis. The incidence of inner ear involvement and arthritis in these patients was lower than that in Caucasians. Female patients seem to have milder inflammation and a better visual prognosis.

Increased Expression of IL-23 Receptor (IL-23R) in Vogt-Koyanagi-Harada (VKH) Disease.

OBJECTIVE: Vogt-Koyanagi-Harada (VKH) disease is an autoimmune disease mediated by T cells that target melanocytes. It has been shown that IL-23 receptor (IL-23R) signaling promotes the generation of pathogenic T helper 17 cells. The aim of this study was designed to detect the possible role of IL-23R in VKH disease. METHODS: Subjects were divided into an active and inactive VKH patient group and a normal control group. The IL-23R level in peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry and real-time polymerase chain reaction. PBMCs were stimulated with serum from patients or controls to detect the influence of serum from VKH patients on IL-23R expression. RESULTS: The IL-23R mRNA level was markedly increased in PBMCs from the active VKH patient group as compared to normal controls. Flow cytometry analysis showed that there was also an elevated IL-23R protein level in PBMCs in active VKH patients. The IL-23R protein level was higher in PBMCs obtained from healthy controls when they were cultured with serum from active VKH patient as compared to cell cultured with serum from normal controls. After the intraocular inflammation in VKH patients was controlled, the IL-23R gene expression returned back to normal levels. CONCLUSION: Our study suggests that an elevated IL-23R level may participate in the development of VKH disease.

Decreased expression of A20 is associated with ocular Behcet's disease (BD) but not with Vogt-Koyanagi-Harada (VKH) disease.

PURPOSE: A20 is a ubiquitously expressed and inducible cytosolic protein, which plays an important role in the negative regulation of inflammation and immunity. In this study, we investigated the role of A20 in Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) disease. METHODS: The levels of A20 in peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs) were detected in BD patients with active and inactive uveitis, VKH patients with active and inactive uveitis, and normal subjects, respectively, by real-time PCR. The effect of A20 silencing was performed by transduction of DCs with adenovirus containing an A20 shRNA vector. The effect of A20 silencing on the maturation of DCs was measured by flow cytometry. The effect of A20 silencing of DCs on cytokine production by DCs and CD4+ T cells was analysed by ELISA. The phosphorylation levels of JNK, p38 and ERK1/2 were detected by flow cytometry. RESULTS: The expression of A20 was markedly decreased in PBMCs and DCs obtained from BD patients with active uveitis, but not in patients with VKH disease as compared with normal controls. Silencing of A20 significantly increased the levels of interleukin (IL)-1ß and IL-6 and suppressed the expression of the anti-inflammatory cytokines IL-10 and IL-27. Downregulation of A20 also led to an increase in IL-17 production by CD4+ T cells. However, downregulation of A20 in DCs did not have an effect on cell surface markers such as CD40, CD80, CD83, CD86 and HLA-DR. Silencing of A20 caused an increased expression of phospho-JNK and phospho-MAPK p38 but not phospho-ERK1/2. CONCLUSIONS: This study showed that the expression of A20 was decreased in BD patients with active uveitis but not in VKH disease. Decreased expression of A20 may lead to an enhanced activation of proinflammatory Th17 cells, causing a reactivation of BD.

Clinical Features and Complications of Scleritis in Chinese Patients.

PURPOSE: To characterize the clinical features of scleritis in Chinese patients. METHODS: The history, demographics, ocular findings, auxiliary examination findings, complications, systemic diseases and therapeutic effects were analyzed retrospectively. RESULTS: The study included 124 male and 169 female patients with scleritis. Anterior and posterior scleritis were, respectively, found in 243 and 42 patients. The other eight patients had both anterior and posterior involvement. The mean age of scleritis onset was 39.4 years. Systemic diseases associated with scleritis mainly included rheumatoid arthritis (RA) (4.4%), ankylosing spondylitis (AS) (3.4%), and tuberculosis (1.7%). Anterior uveitis (23.7%), complicated cataract (16.7%), and intraocular hypertension (12.6%) were common complications of scleritis. Scleritis was controlled in 94.6% of the patients treated with corticosteroids combined with immunosuppressive agents. CONCLUSIONS: Diffuse anterior scleritis was the most common scleritis entity in China. RA and AS were relatively common diseases associated with scleritis. Corticosteroids combined with immunosuppressive agents effectively controlled the disease.

Novel treatment regimen of Vogt-Koyanagi-Harada disease with a reduced dose of corticosteroids combined with immunosuppressive agents.

PURPOSE: To investigate the effectiveness, visual outcome, and prognostic factors of Vogt-Koyanagi-Harada (VKH) disease treatment with a reduced dose of corticosteroids combined with immunosuppressive agents. METHODS: The clinical characteristics, auxiliary examinations, treatment result, visual outcome, and prognostic factors in VKH patients were analyzed. RESULTS: A total of 998 VKH patients were divided into posterior uveitis group (Group1), anterior uveal involvement group (Group 2), and recurrent granulomatous anterior uveitis group (Group 3). Reduced doses of corticosteroids combined with immunosuppressive agents were used for 1-1.5 years. Uveitis was controlled in 100%, 100%, and 96.8% of these three groups, respectively. Visual improvement and stability was observed in 98.1%, 96.5%, and 88.3%, respectively. Treatment after disease onset, visual acuity at first visit, and 1 month after treatment was positively associated with BCVA at last visit (p < 0.05). CONCLUSION: A reduced dose of corticosteroids combined with immunosuppressive agents effectively controlled the intraocular inflammation and improved visual acuity in most Chinese VKH patients.

Clinical features of HLA-B27-positive acute anterior uveitis with or without ankylosing spondylitis in a Chinese cohort.

AIMS: To characterise the clinical features of human leucocyte antigen (HLA)-B27+acute anterior uveitis (AAU) patients with or without ankylosing spondylitis (AS) and investigate the retinal vascular involvement in these patients. METHODS: A total of 1056 HLA-B27+ AAU patients (1525 eyes) were retrospectively studied from April 2008 to February 2016. Patients were divided into human leucocyte antigen (HLA)-B27+AS+ and HLA-B27+AS- group. Clinical features including the onset of uveitis, laterality, the age at first attack, clinical examinations, best corrected visual acuity (BCVA), abnormalities in fundus fluorescence angiography (FFA) and complications were determined and compared between these two groups. RESULTS: There were 581 (55.0%) and 475 (45.0%) patients respectively classified into HLA-B27+AS+ and HLA-B27+AS- group. Males had a higher prevalence than females in the HLA-B27+AS+ group (75.2%) as compared with the HLA-B27+AS- group (51.8%, p<0.001). The HLA-B27+AS+ patients showed a higher percentage of bilateral/alternating involvement (47.3%) as compared with the HLA-B27+AS- group (36.6%, p=0.001). A higher percentage of fibrinous exudation, synechiae as well as complications including complicated cataract and secondary glaucoma were found in the HLA-B27+AS+ group as compared with the HLA-B27+AS- group. Worse visual outcome as indicated by a higher percentage of patients with BCVA <0.5 and with BCVA <0.05 was noted in the HLA-B27+AS+ group as compared with the HLA-B27+AS- group both before and after treatment. FFA showed mild capillary fluorescence leakage in the late phase with indistinctly defined margins on the peripheral retina in 39.3% of HLA-B27+ AAU patients. There was no difference concerning the retinal vascular involvement between these two groups. CONCLUSIONS: Our study confirmed that HLA-B27+AS+ patients show a higher percentage of males, more common bilateral involvement, a higher frequency of fibrinous exudates, synechiae and secondary glaucoma as compared with HLA-B27+AS- patients. Visual outcome was poorer, possibly due to the higher prevalence of complicated cataract in HLA-B27+AS+ patients. Retinal vascular involvement was not uncommon in HLA-B27+ AAU patients.

Increased Complement 3a Receptor is Associated with Behcet's disease and Vogt-Koyanagi-Harada disease.

Behcet's disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic and recurrent autoimmune diseases associated with abnormal T cell immune response. Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) have been reported to be involved in T cell mediated autoimmune disease. This study aimed to investigate the role of C3aR and C5aR in these two diseases. The C3aR expression in PBMCs was increased in patients with active BD (aBD) and active VKH (aVKH). No statistical difference was found concerning the expression of C5aR in PBMCs between patients with aBD or aVKH and normal controls. After the intraocular inflammation in BD and VKH patients was controlled, the C3aR expression returned back to normal levels. The serum from patients with aBD and aVKH significantly induced C3aR expression by PBMCs. C3a induced IL-6, IL-1ß and TNF-α secretion, while inhibited the production of IL-10 by monocytes. Activation of C3aR in CD4+T cells could upregulate IL-17 production and inhibit IL-10 production, but had no detectable influence on IFN-γ production. Our data indicates that increased C3aR expression may lead to over activation of the Th17 cell response and may therefore contribute to the pathogenesis of BD and VKH disease.