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Background: Induction of autoantigen-specific Treg cells that suppress tissue-specific autoimmunity without compromising beneficial immune responses is the holy-grail for immunotherapy to autoimmune diseases., Methods: In a model of experimental autoimmune uveitis (EAU) that mimics human uveitis, ocular inflammation was induced by immunization with retinal antigen interphotoreceptor retinoid-binding protein (IRBP). Mice were given intraperitoneal injection of αCD4 antibody (Ab) after the onset of disease, followed by administration of IRBP. EAU was evaluated clinically and functionally. Splenocytes, CD4 + CD25 - and CD4 + CD25 + T cells were sorted and cultured with IRBP or αCD3 Ab. T cell proliferation and cytokine production were assessed., Findings: The experimental approach resulted in remission of ocular inflammation and rescue of visual function in mice with established EAU. Mechanistically, the therapeutic effect was mediated by induction of antigen-specific Treg cells that inhibited IRBP-driven Th17 response in TGF-β and IL-10 dependent fashion. Importantly, the Ab-mediated immune tolerance could be achieved in EAU mice by administration of retinal autoantigens, arrestin but not limited to IRBP only, in an antigen-nonspecific bystander manner. Further, these EAU-suppressed tolerized mice did not compromise their anti-tumor T immunity in melanoma model., Interpretation: We successfully addressed a specific immunotherapy of EAU by in vivo induction of autoantigen-specific Treg cells without compromising host overall T cell immunity, which should have potential implication for patients with autoimmune uveitis., Funding: This study was supported by the Natural Science Foundation of Guangdong Province and the Fundamental Research Fund of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center., Competing Interests: Declaration of Competing Interest Patents (ZL201711202986.0 and ZL201711202988.X) for the reported data are granted in China. The authors have declared that no conflict of interest exists., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Human uveitis is an autoimmune disease of the central nervous system that is characterized by ocular inflammation with the involvement of uveitogenic Th1 and Th17 responses. In experimental autoimmune uveitis (EAU), the animal model for human uveitis, both responses are proven to be critical in disease development. Therefore, targeting both Th1 and Th17 cells has therapeutic implication for disease resolution. IL-27 is a multifunctional cytokine that can either promote or inhibit T cell responses and is implicated in both autoimmune and infectious diseases. The aim of this study is to characterize the role of IL-27/IL-27R signaling in regulating uveitogenic Th1/Th17 responses in EAU. By immunizing IL-27Rα -/- mice and their wild-type (WT) littermates for EAU, we demonstrated that IL-27 signaling deficiency exacerbated EAU with severe ocular inflammation and impairment of visual function. Furthermore, there was a significant increase in the eye-infiltrating Th1 and Th17 cells in IL-27Rα -/- EAU mice compared to WT. Their retinal antigen-specific Th1 and Th17 responses were also significantly increased, as represented by the elevation of their signature cytokines, IFN-γ and IL-17A, respectively. We also observed the upregulation of another pathogenic cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), from effector T cells in IL-27Rα -/- EAU mice. Mechanistic studies confirmed that IL-27 inhibited GM-CSF production from Th17 cells. In addition, the induction of IL-10 producing type 1 regulatory T (Tr1) cells was impaired in IL-27Rα -/- EAU mice. These results identified that IL-27 signaling plays a suppressive role in EAU by regulating multiple CD4 + cell subsets, including the effector Th1 and Th17 cells and the regulatory Tr1 cells. Our findings provide new insights for therapeutic potential in controlling uveitis by enhancing IL-27 signaling.

Objective: Experimental autoimmune uveitis (EAU) represents autoimmune uveitis in humans, among which B10.RIII and C57BL/6 are the frequently used strains in mice, but to date, no study has been reported to compare EAU disease between the two strains. Here we compared the differences in morphology, pathology, visual function of the retinal inflammation and Th1/Th17 immune responses in the EAU models induced by the interphotoreceptor retinoid binding protein (IRBP) between the B10.RIII and C57BL/6 strains, using fundus and histological examinations, optical coherence tomography, electroretinography and immunoassays., Method: EAU induced in B10.RIII mice exhibited a shortterm severe inflammation with massive ocular infiltrates of inflammatory cells and extensive destruction of the retina that culminated in rapid degeneration of the retina and permanent loss of visual function. In contrast, C57BL/6 mice developed chronic inflammation with recurring and persistent retinitis for several months, highlighting moderate scores of disease severity and visual signal in comparison with those in B10.RIII mice. Consistent with the clinical manifestations, increased Th1/Th17 effector responses were detected in the uveitic eyes of B10.RIII strain than those in C57BL/6 strain. These data demonstrate distinguishing features of retinal inflammation and T-cell immune responses involved in IRBP-induced EAU between B10.RIII and C57BL/6 strains., Conclusion: Our findings suggest that the persistent-recurring EAU model induced in C57BL/6 mice may serve as a better tool to represent distinct aspects of human uveitis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Interleukin-1β (IL-1β) is a potent proinflammatory cytokine that plays a critical role in initiating immunoinflammatory responses. In this study, we generated recombinant mouse IL-1β and anti-mouse IL-1β polyclonal antibodies to examine the effect of IL-1β on experimental autoimmune uveoretinitis (EAU), a mouse model for T cell-mediated eye autoimmune disease. Administration of mouse IL-1β by i.p. in the priming phase, but not in the effector phase, of immune response of EAU enhanced disease scores and its related immune responses including DTH, Ag-specific T cell proliferation and the production of IL-17 and IFN-γ. Furthermore, administration of anti-IL-1β antibody in the priming phase reduced EAU scores. These results suggest that IL-1β is an important mediator in the pathogenesis of autoimmune diseases such as uveitis., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: To quantitatively evaluate aqueous flare and cells in patients with Behcet's disease., Methods: This study included 30 Behcet's patients (52 eyes) with active uveitis. The patients were treated with immunosuppressive agents. Aqueous flare and cells were quantified using the laser flare-cell photometry before treatment and 1 and 2 months after treatment., Result: Before treatment, mean aqueous flare (ph/ms) in Behcet's eyes was 25.7 ± 20.5. After treatment, flare values were significantly reduced after 1 and 2 months compared with those before treatment. No significant difference was found between flare values after 1 and 2 months. Before treatment, mean cell counts (cells/0.5 mm(3)) in Behcet's eyes were 23.2 ± 29.4. After treatment, cell counts were also significantly reduced after 1 and 2 months compared with those before treatment. Cell counts were further significantly reduced from 1 to 2 months., Conclusion: Both aqueous flare and cells were significantly increased in Behcet's patients with active uveitis and improved after a two-month treatment. Breakdown of the blood-aqueous barrier lasts longer than aqueous cells in these patients.

Purpose: To investigate the role of CD4(+)CD25(+) Treg cells in the development of experimental autoimmune uveoretinitis (EAU)., Methods: EAU was induced in B10RIII mice by immunization with IRBP(161-180) in complete Freund's adjuvant and evaluated clinically and pathologically on days 0, 7, 14, 21, and 28. Lymphocytes from draining lymph nodes (LNs) were subjected to flow cytometry to analyze the frequency of CD4(+)CD25(+) Treg cells. CD4(+)CD25(+) Treg cells and CD4(+)CD25(-) T cells were separated by means of magnetic-assisted cell sorting and cocultured or crossover cultured for 3 days. Proliferation of CD4(+)CD25(-) T cells was measured using a modified MTT assay. The levels of IFN-gamma and IL-17 in the supernatants were determined by enzyme-linked immunosorbent assay., Results: Clinical and histopathologic results showed a severe intraocular inflammation in the immunized mice. The frequency of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in the draining LN lymphocytes was increased on day 7, reached its peak on day 14, and maintained a high level up to day 42. CD4(+)CD25(+) Treg cells obtained from mice on days 14 and 28 after immunization showed a stronger inhibitory effect on the proliferation of CD4(+)CD25(-) T cells and the production of IFN-gamma by CD4(+)CD25(-) T cells compared with those obtained from control mice. CD4(+)CD25(+) Treg cells did not affect IL-17 production. Transfer of CD4(+)CD25(+) Treg cells obtained from EAU mice was able to suppress EAU induction by IRBP(161-180) that was not observed after transfer of cells from mice that had received CFA alone, suggesting antigen specificity of the Treg response., Conclusions: A significantly increased frequency and immunoregulatory action of CD4(+)CD25(+) Treg cells is associated with the development and regression of EAU, suggesting that CD4(+)CD25(+) Treg cells are induced during EAU and may be involved in its regression.

Purpose: To investigate the role of Foxp3-positive regulatory T cells in the development of experimental autoimmune uveoretinitis (EAU)., Methods: B10RIII mice were immunized with 50 microg IRBP(161-180) in complete Freund's adjuvant (CFA) to induce EAU. EAU was evaluated clinically and pathologically on days 0, 7, 14, 21, and 28. Foxp3 mRNA levels were detected using reverse transcription-PCR (RT-PCR) and the frequencies of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in splenocytes were assessed by flow cytometry at the aforementioned time points., Results: The first clinical signs of EAU were observed on day 8-9, worsened up to day 14, and then gradually resolved. Histopathologic results showed that inflammatory signs occurred on day 7, reached their peak on day 14, and then gradually decreased. The levels of Foxp3 mRNA and the frequencies of CD4(+)Foxp3(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells in splenocytes increased on day 7, reached a peak on day 14, and then maintained at a high level until day 28., Conclusion: An upregulation of Foxp3 expression is induced in EAU and paralleled with disease activity, suggesting a role for this lymphocyte subpopulation in the regression of this experimental uveitis model.

Purpose: CD4(+)CD25(high) regulatory T (Treg) cells have been shown to be involved in the pathogenesis of autoimmune diseases. Vogt-Koyanagi-Harada (VKH) syndrome is an organ-specific autoimmune disease. This study was designed to phenotypically and functionally characterize peripheral blood CD4(+)CD25(high) Treg cells in VKH patients with active uveitis., Methods: Blood samples were taken from 30 patients with active VKH, 19 patients with inactive VKH, and 26 healthy controls. Peripheral blood mononuclear cells were subjected to flow cytometry for analysis of phenotypes of the CD4(+)CD25(high) Treg cells. For functional analysis, CD4(+)CD25(high) Treg cells and CD4(+)CD25(-) T cells were separated by means of magnetic-assisted cell sorting and subsequently cocultured for 6 days. The proliferation of CD4(+)CD25(-) T cells was measured by [(3)H] thymidine incorporation assay. The levels of IFN-gamma, IL-17, and IL-13 in the supernatants were determined by enzyme-linked immunosorbent assay., Results: Significantly decreased frequencies of CD4(+)CD25(high) Treg cells and percentages of FOXP3(+) cells in these Treg cells were shown in patients with active VKH. Treg cells from patients with active VKH showed a significant deficiency in suppressing the proliferation of CD4(+)CD25(-) T cells and inhibiting the production of IFN-gamma and IL-13 by CD4(+)CD25(-) T cells. CD4(+)CD25(high) Treg cells from VKH patients or healthy controls did not markedly inhibit or promote IL-17 production., Conclusions: A significantly decreased frequency and diminished function of CD4(+)CD25(high) Treg cells is associated with active uveitis in patients with VKH syndrome. These results suggest that these dysfunctional CD4(+)CD25(high) Treg cells may play a role in the pathogenesis of uveitis in VKH syndrome.

Purpose: Behçet disease (BD) is a systemic inflammatory disease presumably caused by an autoimmune response. The interleukin (IL)-23/IL-17 pathway has been demonstrated to be involved in the development and maintenance of certain inflammatory diseases. This study was designed to investigate the role of IL-23 and IL-17 in BD., Methods: IL-23p19 mRNA in peripheral blood mononuclear cells (PBMCs) was examined using RT-PCR. The levels of IL-23, IL-17, and IFN-gamma in sera or PBMCs were detected by ELISA. Flow cytometry was used to evaluate the frequencies of IL-17-producing and IFN-gamma-producing T cells and the expression of CD45RO., Results: Results showed that the expression of IL-23p19 mRNA, IL-23, IL-17, and IFN-gamma was markedly elevated in BD patients with active uveitis. The frequencies of IL-17-producing and IFN-gamma-producing T cells from PBMCs were significantly upregulated in BD patients with active uveitis. The increased IL-17 (3.10% +/- 0.53%) in BD patients with active uveitis was primarily produced by CD45RO(+) memory T cells. Recombinant (r) IL-23 could upregulate IL-17 production by polyclonally stimulated PBMCs, whereas interferon (IFN)-gamma downregulated IL-17 production., Conclusions: These findings reveal that the levels of IL-23, IL-17, and IFN-gamma are elevated in BD patients with active uveitis, and they suggest that the IL-23/IL-17 pathway together with IFN-gamma is associated with the active intraocular inflammation in BD patients.

Background: T lymphocytes have been implicated in the development of endotoxin-induced uveitis (EIU). T-bet is a Th1 cell-specific transcription factor that is involved in differentiation and effector functions. The aim of this study was to investigate kinetics of T-bet expression at the mRNA and protein levels during EIU using real-time PCR and whole-mount immunohistochemistry., Methods: A single footpad injection of 200 mug of lipopolysaccharide (LPS) was administered to male Wistar rats in order to induce EIU. Clinical changes were followed by slit-lamp examination. The expression of T-bet mRNA in the spleen was evaluated 0, 8, 16, 24, 48, and 96 h after LPS injection using real-time PCR. Immunohistochemistry was performed on the iris whole-mounts as well as on frozen sections of the spleen to evaluate T-bet protein expression. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was performed on the iris whole-mounts to assay apoptotic cells., Results: Uveitis was observed in all rats that received LPS. T-bet(+) cells and TUNEL(+) cells in the iris whole-mounts showed a similar pattern in cell number and distribution and both types of cells were observed at 8 h, significantly increased 24 h, and decreased 48 h after LPS injection. T-bet expression at both the mRNA and protein levels in spleen also paralleled ocular inflammation. It was weakly detectable after 0 h, increased after 8 h (index 1.3, T-bet(+) cells OD 17.43+/-2.15), reached its peak after 24 h (index 4.00, OD 53.52+/-4.00), and decreased 48 h following LPS injection (index 1.38, OD 25.75+/-2.45)., Conclusions: The results show that T-bet expression in both the iris and the spleen, and in apoptotic cells in the iris parallel the severity of intraocular inflammation after systemic LPS administration. These results suggest that T-bet may play a significant role in the dynamics of EIU.

Purpose: To study the expression of inducible co-stimulator (ICOS) and its association with T cell effector function in experimental autoimmune uveoretinitis (EAU)., Methods: Eighteen Lewis rats were immunized by retinal S-antigen (50 microg) emulsified in complete Freund's adjuvant (CFA). Twelve normal rats served as normal controls and 18 receiving injection of CFA and PBS as CFA controls for studying the influence of CFA on the expression of ICOS in CD4+CD25+ T cells. ICOS expression on cells from the spleens, inguinal nodes and retinae on day 0 (normal rats), 7, 13 and 21 was investigated using fluorescent quantitative real-time-PCR and Western blot. Expression of B7RP-1, an ICOS ligand, was also studied by Western blot. The phenotype of the cells from the aforementioned three tissues was identified with flow cytometry using antibodies to ICOS, CD4 and CD25. ICOS+ cells from the lymph nodes, and spleens on day 13 were magnetically sorted and cultured with S-antigen to study the cytokines production with enzyme-linked immunosorbent assay., Result: An obvious uveitis was induced in all the immunized rats on day 13 after S-antigen immunization. The mRNA and protein of ICOS were scarcely detectable in normal rat spleens. In EAU rats, an up-regulation of ICOS could be observed on day 7 and was very pronounced on day 13, followed by a decrease on day 21 in the spleens, draining nodes and retinae. Similarly, B7RP-1 expression seemed to be up-regulated during EAU. Flow cytometry showed that ICOS+ cells were mostly CD4 positive. Kinetics of ICOS+CD4+CD25+ T cells was similar to that of ICOS+ cells. CFA alone was also able to induce increased expression of ICOS in CD4+CD25+ T cells. IFN-gamma was secreted predominantly by ICOS+ T cells., Conclusion: ICOS expression is up-regulated in association with T cell effector capacity in EAU. It is presumed that the ICOS/B7RP-1 costimulatory pathway may play a role in the development of EAU.

Purpose: To address the clinical pattern and characteristics of uveitis in a tertiary center for uveitis in China and compare the similarity and difference in the distribution of uveitis entities between China and other countries., Methods: A retrospective study was performed on the patients with uveitis referred to the Zhongshan Ophthalmic Center from January 1996 to December 2003. The clinical data including category, etiology, gender, and the age of the patients at uveitis presentation were analyzed and compared with studies published previously from other countries., Results: There were 902 male and 850 female patients in our series. The mean age of these patients at uveitis presentation was 33.8 +/- 16.5 years. Anterior uveitis (800, 45.6%) was the most common anatomical entity, followed by panuveitis (727, 41.5%), posterior uveitis (119, 6.8%), and intermediate uveitis (106, 6.1%). Further classification with the etiology criteria revealed 16 entities in anterior uveitis, with idiopathic anterior uveitis being the most common entity (473, 27.0%). Twelve entities were identified in panuveitis, of which Behçet disease (289, 16.5%) and Vogt-Koyanagi-Harada (VKH) syndrome (278, 15.9%) were the predominant ones. No specific entity was recognized in the intermediate uveitis group. Although a number of specific entities were identified in posterior uveitis, toxoplasmosis was noted in only two patients in this group., Conclusions: Idiopathic anterior uveitis, Behçet disease, and VKH syndrome are the most common entities of uveitis in China. Ocular toxoplasmosis, ocular histoplasmosis, and birdshot retinochoroidopathy are less common or absent in China.

Objective: To compare the effectiveness of therapeutic regimen in Vogt-Koyanagi-Harada (VKH) syndrome and determine the reasonable regimen for different patients., Methods: Data of 82 patients with VKH syndrome, coming from all over China and referred to Zhongshan Ophthalmic Center from January 1996 to December 2000 were retrospectively analyzed. Twenty-eight patients (56 eyes) with first attack of the intraocular inflammation were treated with oral prednisone for more than one year, whereas 54 patients (108 eyes) with recurrent episodes were treated with chlorambucil for more than one year. All patients were treated with a combination of these immunosuppressives with traditional Chinese medicine herbs, and followed up more than one year after systemic treatment. The previous treatment for these 54 patients was also analyzed in an attempt to compare these results with those presented here., Results: Uveitis was completely controlled in 96.4% of the patients treated with oral prednisone, and all of these patients showed improved vision after treatment. A complete control of uveitis was achieved in 94.4% and improved vision was seen in 88.0% of the patients treated with chlorambucil. All of these 54 patients, although treated with longer but intermittent systemic corticosteroids before installation of chlorambucil, showed a chronic or recurrent uveitis and most cases had markedly decreased vision as compared with those treated by us with regular systemic corticosteroids., Conclusions: Intensive and prolonged systemic treatment with corticosteroids is recommended for the patients with first attack of VKH syndrome, where as regular treatment with chlorambucil is useful for control of chronic and recurrent uveitis seen in VKH syndrome. Traditional Chinese medicine herbs may be helpful in amelioration of uveitis and reduction of side effects of immunosuppressives.

Objective: The purpose of this study was to investigate the uveitogenic activity of autoantigen in the bovine iris-ciliary body., Methods: Urea soluble fraction of boveine melanin associated antigen (USF-BMAA) was isolated from the bovine iris-ciliary body biochemically and determined by SDS-PAGE as well as amino acid analysis. Lewis rats and F344 rats were immunized with USF-BMAA emulsified with equal volume complete Freud's adjuvant and Bordetella pertussis., Results: A strongly stained protein band was observed in the USF-BMAA by SDS-PAGE whose molecular weight is approximate 64 000. Amino acid analysis of USF-BMAA showed that it contains 17 kinds of amino acids with high content of Glu, Leu and Asp. The experimental melanin associated antigen-induced uveitis (EMIU) was successfully incited in both eyes of the Lewis and F344 rats. The inflammation was mainly located in the anterior uvea, and spontaneously recovered. Mild focal choroiditis was present in the rats with severe lesion. However, the inflammation was not observed in the retina and pineal gland., Conclusions: USF-BMAA may be the major part of autoantigen of the uveal tract with uveitogenic activity. Unlike experimental autoimmune uveoretinitis (EAU) which is incited by the retinal soluble antigen (S-Ag) in the rats, no involvement of the retina and pineal gland is found in EMIU.

Interleukin-28A (IL-28A), a member of type III interferons (IFN-λs), promotes antiviral, antitumor and immune responses. However, its ability to regulate autoimmune diseases is poorly understood. In this study, we examined the effect of IL-28A on retinal antigen-induced experimental autoimmune uveoretinitis (EAU), a mouse model of human T-cell-mediated autoimmune eye disease. We found that administration of IL-28A enhanced EAU scores and autoimmune response parameters including delayed-type hypersensitivity (DTH), Ag-specific T cell proliferation and the production of Ag-specific IL-17 and IFN-γ in the priming phase. The effect of IL-28A was abrogated by administration of a neutralizing antibody against IL-28A. Our results suggest that IL-28A is capable of exacerbating a T-cell-mediated autoimmune disease. Thus, targeting IL-28A may provide a new therapeutic approach to T cell-mediated autoimmune diseases such as uveitis. [ABSTRACT FROM AUTHOR]

Abstract: Viral components can trigger autoimmunity, but the involved mechanisms remain to be elucidated. Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and appears to play an important role in this context. Our previous studies showed that signaling of TLR2, TLR3, TLR4 and TLR9 is highly redundant in the adjuvant effect needed to induce experimental autoimmune uveitis (EAU), an animal model of human autoimmune eye disease. In this study, we analyzed the effects of systemic delivery of polyinosinic:polycytidylic acid (poly(I:C)), a mimic of viral dsRNA, in the induction of EAU. We found that TLR3 agonist poly(I:C) enhanced EAU scores, DTH responses and Ag-specific T cell proliferation. In addition, Ag-specific Interleukin 17 (IL-17) and interferon gamma (IFN-γ) production by draining lymph node cells was markedly increased in the poly(I:C)-treated group. Our results suggest that activation of innate immune system mediated by TLR3 signaling pathway is of importance in the pathogenesis of virus-induced autoimmune diseases. [Copyright &y& Elsevier]

Purpose: This study aimed to investigate dynamic changes in the anterior segment in patients with acute anterior uveitis (AAU) using ultrasound biomicroscopy (UBM). Methods: Acute anterior uveitis was diagnosed in 18 patients according to history and ocular examinations. Ultrasound biomicroscopy was performed and the results at three time-points (within 2 weeks of the uveitis attack, and at 2−4 weeks and 6 weeks after it) were analysed. The relationships between clinical manifestations and UBM findings were also evaluated. Results: All investigated AAU patients showed severe ciliary injection, numerous dust keratic precipitates (KPs), aqueous flare and inflammatory cells, and were treated predominantly with corticosteroid and cycloplegic eyedrops. Ultrasound biomicroscopy showed a large number of cells in the anterior and posterior chamber, marked oedema and exudates in and around the iris and ciliary body within 2 weeks of AAU onset. These abnormalities were dramatically improved at 2−4 weeks and almost resolved at 6 weeks and thereafter. Conclusions: Ultrasound biomicroscopy reveals severe inflammatory changes in and around the ciliary body in patients with AAU. These signs rapidly resolve upon treatment. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies in Caucasian uveitis patients have shown an association with the −2518 A/G polymorphism of the monocyte chemoattractant protein (MCP)–1 gene. It is unknown whether this polymorphism is also associated with ocular Behçet''s disease (BD) in Chinese populations. The aim of the current study was therefore to investigate the possible involvement of MCP-1 in the susceptibility to ocular BD in Chinese Han individuals. A case control association study was performed in 296 ocular BD patients and 319 geographically and age-matched healthy controls using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Binary logistic regression analysis revealed a decreased frequency of the homozygous AA genotype and an increased frequency of AG genotype of the MCP-1 −2518 polymorphism in ocular BD patients compared with healthy controls, when adjusted for gender (p = 0.048, p = 0.028, respectively). However, when segregated on the basis of several clinical findings, no any association was found between this polymorphism and ocular BD. In conclusion, the present study suggests that the MCP-1 −2518 AA genotype seems to display a protective association with ocular BD, whereas the −2518 AG genotype might be a susceptible factor for ocular BD in the Chinese Han population. [Copyright &y& Elsevier]