Increased CD40 ligand in patients with acute anterior uveitis

PURPOSE: The inflammatory response in acute anterior uveitis (AU) is believed to be primarily mediated by autoreactive T-cells. We wanted to evaluate whether the T-cell activation marker CD40 ligand is involved in the AU immunopathogenesis. METHODS: We evaluated the expression of the CD40 ligand on CD4+ T-cells, CD8+ T-cells and CD19+ B-cells on peripheral blood mononuclear cells using flow cytometry in six patients with unilateral AU, six patients with monosymptomatic optic neuritis (ON) as inflammatory controls, and in six healthy controls. The ex vivo induction of the CD40 ligand on T-cells in patients and controls was also studied. RESULTS: A significantly higher expression of the CD40 ligand on both CD4+ (p < 0.05) and CD8+ (p < 0.05) T-cells in patients with AU compared to ON patients and healthy controls was found. There was a significantly higher induction of the CD40 ligand on CD8+ T-cells in AU patients compared to ON patients and healthy controls (p < 0.01). No differences in the B-cell population were observed between the three groups. CONCLUSION: Patients with AU had increased expression of the CD40 ligand on T-cells in the blood and expressed higher levels of the CD40 ligand when stimulated, compared to ophthalmological inflammatory controls and healthy controls. The data suggest that the CD40 ligand is involved in the development of AU.     

Interferon-alpha: a key factor in autoimmune disease?

PURPOSE: Interferon (IFN)-alpha is an effective drug for treatment of uveitis in Beh?et's disease. This study was undertaken to investigate the mechanism of action of IFN-alpha in the treatment of various types of noninfectious sight-threatening uveitis. METHODS: Eleven patients with refractory uveitis, and 13 healthy individuals were enrolled. The number of circulating plasmacytoid dendritic cells (pDCs) and their capacity to produce IFN-alpha in culture on stimulation with synthetic oligodinucleotides containing the CpG-motif were studied. Peripheral blood CD4+ T-cell phenotype and activation status were evaluated by flow cytometry at 0, 2, and 8 weeks after treatment for expression of CD69, CD62L, chemokine receptors (CCR4, CXCR3, and CCR5), and intracellular cytokines (TNF-alpha, IFN-gamma, and IL-10). RESULTS: All patients experienced a positive clinical response to IFN-alpha treatment. There was no significant difference between patients and control subjects in the number of circulating pDCs, but there was a significant decrease in the capability of patients' pDCs to produce IFN-alpha in response to CpG (P < 0.001). Peripheral blood CD4+ T cells expressed reduced levels of surface CD62L (P < 0.005) as a measure of activation and higher levels of chemokine receptors CXCR3, CCR4, and CCR5 (P < 0.005, P < 0.05, and P < 0.05, respectively); in addition, intracellular T-cell IL-10 levels were increased once the treatment was initiated (P < 0.01). CONCLUSIONS: The data suggest that IFN-alpha may control uveitis by promoting induction of IL-10-producing T-cells, possibly T-regulatory cells. Dysregulation of the T-cell population in patients with uveitis may be associated with a defect in the pDCs' ability to produce IFN-alpha, which can be circumvented with administration of exogenous IFN-alpha.     

Systemic CD4(+) T cell phenotype and activation status in intermediate uveitis

AIM: To investigate peripheral blood lymphocyte phenotype in patients with intermediate uveitis using CD69, chemokine receptor, and cytokine expression. METHODS: Peripheral blood lymphocytes of 18 patients with idiopathic intermediate uveitis and 6 patients with presumed sarcoid intermediate uveitis were evaluated for CD4(+) T cell expression of CD69, CCR4, CCR5, CXCR3 and the intracellular cytokines IFNgamma, TNFalpha, and interleukin (IL)-10 by flow cytometry, and for IL-2, IL-4, IL-5, IL-10, IFNgamma, and TNFalpha production following unstimulated and activated culture using cytokine bead array and compared with healthy control subjects. RESULTS: The expression of CD69 and TNFalpha by peripheral blood CD4(+) lymphocytes of patients with idiopathic intermediate uveitis and presumed sarcoid intermediate uveitis was significantly higher than control subjects (p = 0.002 and p<0.05, respectively). The ratios of the concentrations of IL-2:IL-5 and IFNgamma:IL-5 in supernatants of activated peripheral blood lymphocyte cultures were significantly higher in patients with presumed sarcoid intermediate uveitis than control subjects. CONCLUSIONS: This study implicates TNFalpha in the pathogenesis of intermediate uveitis, highlighting the potential role of anti-TNF treatments for this disease. Studies of Th1:Th2 cytokine ratios suggested polarisation of the immune response towards Th1 in presumed sarcoid intermediate uveitis despite clinically quiescent systemic disease.     

Combined low dose cyclosporine and prednisone down-regulate natural killer cell-like effector functions of CD8brightCD56+ T cells in patients with active Behçet uveitis

PURPOSE: To investigate the changes of effector-related phenotypic markers and the natural killer (NK)-like effector functions of CD8(bright)CD56+ T cells in patients with Beh?et uveitis after combined cyclosporine and prednisone (Cs/Pd) treatment. METHODS: Ten patients with active Beh?et panuveitis and 10 healthy controls were prospectively recruited in this study. The effector-related surface markers (CD27, CD62L, CD11b, HLA-DR, CD94, NKG2D), chemokine receptors (CXCR1, CXCR3, CCR4, CCR5), and intracellular perforin of circulating CD8(bright)CD56+ T cells were determined by flow cytometric analysis before and after two months' treatment. NK-like cytotoxicity of ex vivo CD8(bright)CD56+ T cells against K562 was measured by standard 51Cr release assay. RESULTS: The expression levels of effector-related molecules on CD8(bright)CD56+ T cells normalized after treatment. The expression levels of CXCR1 and CCR5 were down-regulated on CD8(bright)CD56+ T cells after treatment. The amounts of preformed intracellular perforin of CD8(bright)CD56+ T cells were reduced to the normal levels. Furthermore, the NK-like cytolytic capacities of CD8(bright)CD56+ T cells were decreased after treatment. CONCLUSIONS: Our results suggest that the combined Cs/Pd treatments in active Beh?et uveitis may downregulate the NK-like effector functions of CD8(bright)CD56+ T cells.     

Combined Low Dose Cyclosporine and Prednisone Down-Regulate Natural Killer Cell-Like Effector Functions of CD8brightCD56+ T Cells in Patients with Active Behçet Uveitis

Purpose: To investigate the changes of effector-related phenotypic markers and the natural killer (NK)-like effector functions of CD8^brightCD56+ T cells in patients with Behçet uveitis after combined cyclosporine and prednisone (Cs/Pd) treatment. Methods: Ten patients with active Behçet panuveitis and 10 healthy controls were prospectively recruited in this study. The effector-related surface markers (CD27, CD62L, CD11b, HLA-DR, CD94, NKG2D), chemokine receptors (CXCR1, CXCR3, CCR4, CCR5), and intracellular perforin of circulating CD8^brightCD56+ T cells were determined by flow cytometric analysis before and after two months' treatment. NK-like cytotoxicity of ex vivo CD8^brightCD56+ T cells against K562 was measured by standard ⁵¹Cr release assay. Results: The expression levels of effector-related molecules on CD8^brightCD56+ T cells normalized after treatment. The expression levels of CXCR1 and CCR5 were down-regulated on CD8^brightCD56+ T cells after treatment. The amounts of preformed intracellular perforin of CD8^brightCD56+ T cells were reduced to the normal levels. Furthermore, the NK-like cytolytic capacities of CD8^brightCD56+ T cells were decreased after treatment. Conclusions: Our results suggest that the combined Cs/Pd treatments in active Behçet uveitis may downregulate the NK-like effector functions of CD8^brightCD56+ T cells.     

Etiology and clinical features of anterior uveitis in southern croatia (dalmatia)

Patients with endogenous uveitis represent 6.5+ of patients in University Hospital Split, which serves most of South Croatia. Within a four-year period 208 patients were treated for endogenous uveitis. Results of clinical-laboratory examinations and treatment of 112 subjects suffering from anterior uveitis are presented and compared. Acute anterior uveitis (AAU) was the commonest form of uveal inflammation. It was present in 49+ of all uveitis cases and in 91.1+ of all anterior uveitis cases (AU). 67.6+ of the subjects with AAU had and 32.4+ did not have the HLA B(27) antigen. The inflammatory pattern in B(27)(+) patients was typical of B(27)(+) AAU. Patients with B(27)(+) AAU exhibited the same inflammatory pattern as those with B(7)(+) AAU. B(27)(+) AAU patients had significantly more systemic/rheumatic diseases (p>0.05), while patients with B(27)(-) AAU had significantly more infectious diseases (p>0.05). Forty percent of the patients with chronic anterior uveitis suffered from juvenile rheumatoid arthritis. The authors observed the rise in peripheral blood IgG, IgA, IgM, CD(2)(+), CD(4)(+) and B cells during the acute phase of AAU. Normalization of B cells (CD(20)(+)) was observed in early remission of anterior uveitis, about eight weeks after the onset of the disease.     

Expression of CC chemokines and their receptors in the eye in autoimmune anterior uveitis associated with EAE.

PURPOSE: To determine the pattern of expression of CC chemokines and their receptors in the eyes of Lewis rats and to establish their role in autoimmune anterior uveitis (AU) associated with experimental autoimmune encephalomyelitis (EAE). METHODS: EAE/AU was induced in Lewis rats with myelin basic protein in complete Freund's adjuvant (CFA). The rats were scored for the development of clinical EAE and AU. The expression of CCL5/regulated on activation normal T-cell expressed and secreted (RANTES), CCL2/monocyte chemotactic protein (MCP)-1, CCL3/macrophage inflammatory protein (MIP)-1alpha, and CCL4/MIP-1beta and their receptors was examined at the preclinical stage, onset, peak, and recovery by RT-PCR and ELISA. EAE/AU rats were treated with neutralizing polyclonal antibodies against CCL3/MIP-1alpha, CCL4/MIP-1beta, CCL2/MCP-1, and CCL5/RANTES and tested for the suppression of onset of clinical AU and EAE. The control group received normal rabbit IgG at the same dose. RESULTS: The gene expression of those chemokines was upregulated concurrently with symptom onset of EAE/AU and correlated with the intensity of inflammatory changes in the eye and central nervous system (CNS). The highest expression of CCL4/RANTES, CCL2/MCP-1, and CCL3/MIP-1alpha in the eye was detected at onset of clinical uveitis, whereas CCL4/MIP-1beta was elevated at the peak of AU. The expression of chemokine receptors associated with T-helper (Th)1-type response, CCR1 and CCR5, correlated with their appropriate ligands and was the highest at the peak of AU, whereas CCR2, the receptor for CCL2/MCP-1, was present before the onset of the disease. Treatment of anti-MIP-1beta and anti-MCP-1 significantly delayed the onset and shortened the duration of AU and EAE. Anti-MIP-1alpha treatment had no effect on clinical EAE but inhibited the clinical signs of AU. Although CCL5/RANTES expression was observed during the entire course of the disease, anti-RANTES treatment had no effect on clinical disease progression. CONCLUSIONS: The data suggest that CCL2/MCP-1, CCL3/MIP-1alpha, and CCL4/MIP-beta contribute to the recruitment of inflammatory cells into the eye and CNS and to disease activity.     

Th1 and Th2 responses on the ocular surface in uveitis identified by CCR4 and CCR5 conjunctival expression

PURPOSE: To investigate CC chemokine receptor 4 (CCR4) and CC chemokine receptor 5 (CCR5) expression, known to be related to the Th2 and Th1 inflammatory pathways, respectively, and human leukocyte antigen-D related (HLA-DR) antigens as hallmarks for ocular surface inflammation in patients with uveitis using conjunctival impression cytologic specimens. DESIGN: Case-controlled study. METHODS: Conjunctival impression cytologic specimens were obtained from patients with anterior uveitis (n = 26), and their inflammatory profile was compared with those of patients with vernal keratoconjunctivitis (VKC; n = 24), keratoconjunctivitis sicca (KCS; n = 17), and normal subjects (n = 17). Expressions of CCR4, CCR5, and HLA-DR were analyzed using flow cytometry and were expressed by determining the percentage of cells expressing the markers in the conjunctival epithelium. RESULTS: CCR4 was overexpressed in the uveitis group (mean, 19.8% +/- 19.7% of positive cells) and in the VKC group (24.7% +/- 20.1%). CCR5 was expressed only weakly in uveitis patients (6.4% +/- 13.1%) and in the normal subjects (2.4% +/- 2.4%). HLA-DR expression by conjunctival cells was increased in the uveitis patients (57.4% +/- 21.1%) and in the KCS group (52.4% +/- 12.1%) compared with the VKC group (23.9% +/- 26.8%; P < .001) and normal subjects (22.1% +/- 19.1%; P < .001). CONCLUSIONS: CCR4, classically related to the Th2 system, and HLA-DR both were overexpressed by the conjunctival epithelium in uveitis patients, whereas CCR5, related to the Th1 system, was expressed weakly in uveitis patients. These preliminary results seem to suggest an involvement of the Th2 system on the ocular surface in uveitis. Exploration of the ocular surface in uveitis may represent a new way to understand better the immune pathways involved in this complex disease.     

Chemokine receptor expression in peripheral blood monocytes from patients with neovascular age-related macular degeneration

Purpose. Chemokine signaling and monocytes/macrophages were implicated in the pathogenesis of AMD. We tested the association between chemokines involved in monocyte recruitment and AMD. Methods. Immunophenotyping for white blood cell (WBC) populations including CD14++CD16- and CD14+CD16+ monocytes, CD19+, CD3+, and CD16+ lymphocytes, and chemokine receptors CCR1, CCR2, CCR5, CX(3)CR1, and CXCR4 was performed on peripheral blood from treatment-na?ve neovascular AMD (NV-AMD) patients and controls. The mRNA level of chemokine receptors in monocytes was measured with quantitative-PCR. Systemic levels of major chemokine ligands CCL2, CCL5, CCL3, and CXCL10 were evaluated by ELISA. Genotyping was performed for risk SNPs for AMD in the CFH, C3, and HTRA1 genes. Results. The percentage of WBC subpopulations tested was similar between NV-AMD patients (n = 18) and controls (n = 20). CD14+CD16+ monocyte subpopulation showed a 3.5-fold increased expression of CCR1 (P = 0.039; t-test) and a 2.2-fold increased expression of CCR2 (P = 0.027) in patients compared with controls. Increased CCR1 and CCR2 expression was correlated with each other in patients (R(2) = 0.64, P < 0.0001), but not controls (R(2) = 0.02, P = 0.57). Increased mRNA levels of CCR1 (1.6-fold, P = 0.037) and CCR2 (1.6-fold, P = 0.007) were found in monocytes from NV-AMD patients. Chemokine receptor expression was not correlated with the presence of risk SNPs, and was not associated with blood chemokine levels. Conclusions. CCR1 and CCR2 are coupregulated on the CD14+CD16+ monocyte population in NV-AMD patients. These data implicate CD14+CD16+ monocytes and chemokine signaling in AMD. Additional investigation is needed to elucidate the role of these monocytes and their potential as a biomarker or therapeutic target for AMD.     

Anti-TNFalpha therapy modulates the phenotype of peripheral blood CD4+ T cells in patients with posterior segment intraocular inflammation

PURPOSE: Posterior segment intraocular inflammation (PSII) is a putative Th1 CD4+ cell mediated autoimmune disorder. In experimental autoimmune uveoretinitis, neutralization of tumor necrosis factor (TNF)-alpha induces suppression of Th1 cells, macrophage activation, and target organ damage. Previous studies implicated an efficacy of anti-TNFalpha therapies in patients with PSII. This study investigated the immunomodulatory effect of anti-TNFalpha therapy to find predictors of effective immunosuppression in PSII. METHODS: Fifteen patients with PSII refractory to conventional immunosuppressive therapy received a single infusion of a recombinant protein generated by fusing the p55 TNFalpha receptor with human IgG1. During 17 treatment periods, visual acuity (logarithm of the minimum angle of resolution [logMAR]) was monitored as a response criterion. Phenotype markers of CD4+ T cells were analyzed before and 2, 4, and 12 weeks after therapy. Expression of intracellular cytokines (interferon [IFN]-gamma, interleukin [IL]-10, and TNFalpha) and Th1/Th2-specific chemokine receptors (CXCR3, CCR4, and CCR5) on peripheral blood CD4+ T cells was determined using flow cytometry. RESULTS: The fraction of IL-10-expressing CD4+ T cells was increased during 12 of 17 treatment periods within 2 weeks after treatment. During eight treatment periods, this increase was associated with an improvement of visual acuity of at least 0.2 logMAR within 4 weeks (P = 0.029). The ratio between IL-10- and IFNgamma-expressing CD4+ T cells was significantly increased 2 weeks after therapy (P = 0.015). There was no significant change of CXCR3, CCR4, or CCR5 expression. CONCLUSIONS: Neutralizing TNFalpha activity in PSII increases the fraction of peripheral blood CD4+ T cells expressing IL-10, which correlates with a recovery of visual function.     

Increased CD4+ expression and decreased IL-10 in the anterior chamber in idiopathic uveitis.

PURPOSE: To compare cell types and cytokines in aqueous humor from patients with uveitis either occurring in association with a systemic disease or apparently isolated and not associated with a systemic disease. METHODS: Cells were collected by centrifugation of fresh aqueous humor from uveitis and controls, and immunofluorescence techniques were performed with markers for T cells, B cells, and monocytes. Cytokines were measured in the aqueous supernatants, and serum samples were assayed for soluble interleukin-2 receptors. RESULTS: When aqueous samples from idiopathic uveitis were compared with those from uveitis associated with a systemic disease, there were increases in CD3+, CD4+ (p = 0.001), and activated CD4+ T cells (p = 0.02) and a decrease in B cells (p = 0.0013). This was not reflected in the peripheral blood where there were no differences in the cell types or in soluble interleukin-2 receptor levels. No cells were obtainable from control aqueous. Interleukins-10 and -12, interferon-gamma, and transforming growth factor-beta2 were detected in aqueous supernatants. Interleukin-10 was reduced (p = 0.024) in uveitis in comparison with controls. CONCLUSIONS: The results suggest a selective recruitment of CD4+ T cells within aqueous humor but only in idiopathic uveitis. In both disease groups there was a decrease in the immunoregulatory cytokine interleukin-10, which might enable an immune response to occur in an otherwise highly immunosuppressive microenvironment. Increases in activated CD4+ T cells combined with depressed interleukin-10 levels could partially explain why, for example, in acute anterior uveitis, the inflammatory disease is often more severe.     

Phenotypes of T cells infiltrating the eyes in autoimmune anterior uveitis associated with EAE

PURPOSE: Lewis rats immunized with myelin basic protein (MBP) develop experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU), which recurs. The goal was to analyze cellular activation markers and adhesion molecules of T cells that infiltrate the eyes and spinal cord during acute and recurrent AU in actively and passively induced diseases simultaneously in the same animals. METHODS: EAE-AU was induced in Lewis rats by immunization with MBP in CFA, or by adoptive transfer of MBP-specific T-cell lines, and the signs of clinical EAE and AU was scored. Cells isolated from the iris-ciliary body were tested by flow cytometry for expression of CD4, CD8, CD45RC, T-cell receptor (TCR) Vbeta8.2, alpha4 integrin, L-selectin, CD44, and CD134. RESULTS: Ocular T cells showed a significantly higher expression of CD62L (l-selectin) than did T cells in the spinal cord. In addition, a much lower percentage of infiltrating CD8(+) T cells was found in the eyes during AU. In passive transfer experiments, T-cell lines derived from acute and recurrent uveitis showing similar phenotypes differing in specificities but possessed the capacity of inducing both AU and EAE. Pretreatment of rats with effector CD4(+) T cell before MBP immunization did not induce suppression of EAE or AU. However, pretreatment with regulatory CD8(+) T cells significantly reduced the severity and duration of both EAE and AU. CONCLUSIONS: T cells recruited into the inflamed eyes or central nervous system (CNS) are mainly activated/memory T cells expressing different levels of L-selectin. Regulatory CD8(+) T cells may contribute to the susceptibility of the eye to recurrent AU. The differences in phenotypes of T cells recruited simultaneously to two different organs suggest that microenvironment also plays a role in determining lymphocyte homing.     

CD69 expression on peripheral CD4+ T cells parallels disease activity and is reduced by mycophenolate mofetil therapy in uveitis

PURPOSE. To assess the effects of mycophenolate mofetil (MMF) therapy on T helper cell activation status, using CD69 expression and cytokine profile with flow cytometry in relation to clinical activity in uveitis. METHODS. Patients with posterior or intermediate uveitis treated with MMF (n = 10), patients with active uveitis not treated with MMF and receiving no or minimal therapy (n = 10), and healthy volunteers (n = 21) had peripheral blood lymphocyte immunofluorescence analysis for T helper cell (CD4, CD3) markers, activation status (CD69), and intracellular cytokine (interleukin [IL]-2, interferon [IFN]-gamma, and IL-4) levels. Patients were compared before and during MMF therapy in relation to T helper cell activation and clinical activity. RESULTS. Patients with active uveitis not treated with MMF and receiving no or minimal therapy had increased frequency of CD69-positive CD4 T cells (10.5% +/- 4.6%, P = 0.0007) compared with healthy volunteers (3.3% +/- 2.7%). Of all patients receiving MMF therapy, only patients with moderate to severe uveitis activity in the pre-MMF treatment group (n = 5; 15.5% +/- 5.0%, P = 0.004) had increased frequency of CD69-positive CD4 T cells compared with healthy volunteers. During MMF therapy, a significant reduction in frequency of CD69-positive CD4 T cells occurred in patients with prior moderate to severe uveitis activity (to 8.9% +/- 3.8%, P = 0.04). Levels of CD69-positive CD4 T cells in patients who had had inactive or mildly active disease (n = 5) before and during MMF therapy were comparable with levels in healthy volunteers. No significant changes in cytokine levels were found between the patient and control groups. A significant association between changes in frequency of CD69-positive CD4 T cells and changes in visual acuity (P = 0.008) and changes in vitreal haze (binocular indirect ophthalmoscopy score; P = 0.01) was observed in MMF-treated patients with prior moderate to severe uveitis activity. CONCLUSIONS. Reduction in uveitis activity during MMF therapy correlates with reduction in frequency of peripheral blood CD69-positive CD4 cells. The frequency of CD69-positive CD4 T cells is a measure of activity in posterior uveitis and may guide adequate immunosuppression.     

Experimental autoimmune uveoretinitis: characterization of retina infiltrating cells

Summary The chronic model of murine EAU induced by interphotoreceptor retinoid binding protein represents a disease similar to clinical chorioretinitis. In this study we characterized the kinetics of retina infiltrating T-cells, macrophages and expression of the adhesion molecules ICAM-1 and ICAM-2. Methods: B10.A mice were immunized subcutaneously with IRBP, and the eyes were analyzed on days 10, 18, 24 and 28. The infiltrating cells were characterized by mAbs recognizing T-cell receptors (TCR) V?6 and V?8, T-cell markers, macrophages and ICAM-1 and ICAM-2. Results: While CD8 ⁺ T-cells and ICAM-2 were detectable from day 10 (retina is intact) until day 28, CD4 ⁺ T-cells, macrophages and ICAM-1 appear with the onset of retinal destruction. Starting at day 10 the dominating TCR was V?6; V?8 was noticed from day 18 on. Conclusion: CD8 ⁺ T-cells infiltrating the intact retina and stimulating the expression of high endothelial venules (HEVs) could be responsiable for the onset of uveitis.      

Expression of haematogenous and lymphogenous chemokine receptors and their ligands on uveal melanoma in association with liver metastasis

Purpose: Chemokine receptors and their ligands are involved in a number of cell processes, including normal cell trafficking as well as metastasis in cancer. During metastasis, they are thought to play a role in determining cancer cell distribution and target organs. The aim of this study was to examine the expression of the chemokine receptors CXCR4, CCR7 and CCR10 as well as their respective chemokine ligands (CXCL12, CCL19, CCL27) in human uveal melanomas. Methods: Seventy formalin‐fixed paraffin‐embedded uveal melanoma specimens from patients treated in 1996–1997 were examined using immunohistochemistry and evaluated using an immune reactive score (IRS). Results: The chemokine receptors CXCR4, CCR7 and CCR10 were primarily expressed in the cytoplasm of uveal melanoma cells, with CXCR4 (average IRS 8.2) and CCR7 (average IRS 5.7) showing the strongest expression, respectively. The chemokine ligand CCL19 demonstrated a moderate expression (average IRS 5.3), whereas the expression of receptor CCR10 (average IRS of 3.4), ligand CCL27 (average IRS 2.5) and ligand CXCL12 (average IRS 0.6) by uveal melanoma cells was low. A significant association between liver metastases and chemokine expression was found for CCR7 expression (p = 0.037) only. Comparison of liver metastasis and choroid uveal melanoma (35.3%, n = 12 of 34) versus ciliary body involvement (72.7%, n = 8 of 11) was significant (p = 0.030). Conclusion: Chemokine receptors are more strongly expressed on uveal melanoma cells than their ligands. Our results show new aspects of the metastatic process in uveal melanoma.     

Etiology and Clinical Features of Anterior Uveitis in Southern Croatia (Dalmatia)

Patients with endogenous uveitis represent 6.5+ of patients in University Hospital Split, which serves most of South Croatia. Within a four-year period 208 patients were treated for endogenous uveitis. Results of clinical-laboratory examinations and treatment of 112 subjects suffering from anterior uveitis are presented and compared. Acute anterior uveitis (AAU) was the commonest form of uveal inflammation. It was present in 49+ of all uveitis cases and in 91.1+ of all anterior uveitis cases (AU). 67.6+ of the subjects with AAU had and 32.4+ did not have the HLA B₂₇ antigen. The inflammatory pattern in B₂₇⁺ patients was typical of B₂₇⁺ AAU. Patients with B₂₇⁺ AAU exhibited the same inflammatory pattern as those with B₇⁺ AAU. B₂₇⁺ AAU patients had significantly more systemic/rheumatic diseases (p>0.05), while patients with B₂₇^? AAU had significantly more infectious diseases (p>0.05). Forty percent of the patients with chronic anterior uveitis suffered from juvenile rheumatoid arthritis. The authors observed the rise in peripheral blood IgG, IgA, IgM, CD₂⁺, CD₄⁺ and B cells during the acute phase of AAU. Normalization of B cells (CD₂₀⁺) was observed in early remission of anterior uveitis, about eight weeks after the onset of the disease.     

急性前葡萄膜炎患者血清IL-35和TGF-β1表达水平及临床意义

目的:研究急性前葡萄膜炎患者血清IL-35、TGF-β1表达水平变化及两者之间的相关性,探讨IL-35、TGF-β1在急性前葡萄膜炎中的临床意义。方法:纳入2018-05/2019-05在甘肃省人民医院眼科确诊的急性前葡萄膜炎患者30例作为急性前葡萄膜炎组,同期进行体检的健康人30例作为健康对照组,采用ELISA法检测两组受检者血清IL-35、TGF-β1表达水平,并根据改良的EIU临床评分标准评估急性前葡萄膜炎严重程度。结果:急性前葡萄膜炎患者血清IL-35、TGF-β1表达水平显著高于健康对照组(均P<0.05),且急性前葡萄膜炎患者血清IL-35、TGF-β1水平与疾病严重程度无明显相关性(rs=0.087、0.044,均P>0.05),但血清IL-35与TGF-β1表达水平呈正相关(rs=0.637,P<0.001)。结论:血清IL-35、TGF-β1水平变化与急性前葡萄膜炎的发生和发展密切相关,可能在急性前葡萄膜炎中协同发挥免疫抑制作用。     

Disturbed expression of Fas/FasL on CD4+ and CD8+T cells in Behcet's disease,Vogt-Koyanagi-Harada syndrome,and idiopathic anterior uveitis

Aims: To evaluate the expression of Fas/FasL antigen on peripheral blood T lymphocytes in patients with Behcet's disease, Vogt-Koyanagi-Harada (VKH) syndrome, and idiopathic anterior uveitis. Methods: The expression of Fas and FasL on peripheral blood T lymphocytes was determined using flow cytometry in 26 patients with Behcet's disease (BD), 17 patients with VKH syndrome, 25 patients with idiopathic anterior uveitis, and 43 healthy individuals (controls). Results: A higher proportion of CD4 + T cells expressing Fas was noted in patients with Behcet's disease (25.70 ± 7.32%), VKH syndrome (19.60 ± 11.02%), and idiopathic anterior uveitis (20.81 ± 7.40%) compared with controls (14.02 ± 6.30%). The expression of Fas on CD8 + cells from patients with Behcet's disease (9.47 ± 6.97%) and VKH syndrome (6.84 ± 5.5%) was also higher than that seen in controls (3.47 ± 2.75%). There was no difference in FasL expression on T cells between patients and controls except that a lower expression of FasL on CD8+ T cells was noted in patients with idiopathic anterior uveitis. Conclusion: A disturbed expression of Fas and FasL on T cells is present in patients with Behcet's disease, VKH syndrome, and idiopathic anterior uveitis, which may be involved in the perpetuation and recurrence of uveitis.