Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.

Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU))1. How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8+ T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public ß-chain variable region-complementary-determining region 3ß (BV9-CDR3ß) motif2-4 from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3ß TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.

The gut microbiome and HLA-B27-associated anterior uveitis: a case-control study.

BACKGROUND: The human gut microbiome (GM) is involved in inflammation and immune response regulation. Dysbiosis, an imbalance in this ecosystem, facilitates pathogenic invasion, disrupts immune equilibrium, and potentially triggers diseases including various human leucocyte antigen (HLA)-B27-associated autoinflammatory and autoimmune diseases such as inflammatory bowel disease (IBD) and spondyloarthropathy (SpA). This study assesses compositional and functional alterations of the GM in patients with HLA-B27-associated non-infectious anterior uveitis (AU) compared to healthy controls. METHODS: The gut metagenomes of 20 patients with HLA-B27-associated non-infectious AU, 21 age- and sex-matched HLA-B27-negative controls, and 6 HLA-B27-positive healthy controls without a history of AU were sequenced using the Illumina NovaSeq 6000 platform for whole metagenome shotgun sequencing. To identify taxonomic and functional features with significantly different relative abundances between groups and to identify associations with clinical metadata, the multivariate association by linear models (MaAsLin) R package was applied. RESULTS: Significantly higher levels of the Eubacterium ramulus species were found in HLA-B27-negative controls (p = 0.0085, Mann-Whitney U-test). No significant differences in microbial composition were observed at all other taxonomic levels. Functionally, the lipid IVA biosynthesis pathway was upregulated in patients (p < 0.0001, Mann-Whitney U-test). A subgroup analysis comparing patients with an active non-infectious AU to their age- and sex-matched HLA-B27-negative controls, showed an increase of the species Phocaeicola vulgatus in active AU (p = 0.0530, Mann-Whitney U-test). An additional analysis comparing AU patients to age- and sex-matched HLA-B27-positive controls, showed an increase of the species Bacteroides caccae in controls (p = 0.0022, Mann-Whitney U-test). CONCLUSION: In our cohort, non-infectious AU development is associated with compositional and functional alterations of the GM. Further research is needed to assess the causality of these associations, offering potentially novel therapeutic strategies.

A case of severe flare reaction observed in HLA B27 associated acute anterior uveitis.

BACKGROUND: Anterior chamber flare reaction refers to the light reflection from the protein in aqueous humor. We report a case of very severe flare reaction observed in human leukocyte antigen (HLA)- B27 associated acute anterior uveitis (AAU). CASE PRESENTATION: An age 43 male patient visited the uveitis clinic complaining of decreased visual acuity in the right eye which developed 1 week before. The detailed ophthalmic examination revealed very severe flare reaction in the anterior chamber with diffuse conjunctival hyperemia in the right eye. Pupil margin and iris details were barely observable. Oral prednisolone 20 mg daily with topical 1% prednisolone acetate (Pred Forte, Allergan, CA) every 2 h and 1% topical cyclopentolate (Cyclogyl, Alcon, TX) three times daily were immediately prescribed. The next day, the flare reaction of the right eye decreased significantly and inflammatory cells in the anterior chamber were visible. Detailed fundus examination revealed no inflammatory signs on the retina and ciliary body. Later, the blood test revealed positive HLA B27 and autoantibodies against lupus anticoagulant with mild elevation of C reactive protein. There were no signs for ankylosing spondylitis. Continued treatment and tapering of topical 1% prednisolone acetate for 4 weeks led to the complete resolution of the anterior uveitis. CONCLUSIONS: We experienced HLA-B27 AAU with the feature of a very severe flare reaction. Conventional uveitis treatment was successful to acquire the complete resolution of the inflammation.

Allergic inflammation of the anterior surface of the eye.

Background: Ocular allergies affect an estimated 40% of the population, 98% of which are because of allergic conjunctivitis and includes tear film dysfunction. With the current advent of both repurposed drugs for ocular allergies, as well as novel drugs, lubricants and methods of administration, there is a need to update new treatments to optimize the care of ocular allergy patients. Methods: An overview of mediators, clinical characteristics and management is provided in a summary format. Results: Lubricants (best when refrigerated provide immediate relief that is short lived (several minutes) due to its dilutional effect on mediators and pollen in the tear film. Immediate and longer-term benefit occurs from different topical and oral medications - primarily histamine receptor agonists. Conclusion: The newest prescription topical ophthalmic histamine H1 receptor antagonist (an inverse agonist) to be approved by the U.S. Food and Drug Administration in the past 10 years (U.S. NDA approved May 30, 2017) is cetirizine ophthalmic solution for the treatment of ocular itching with allergic conjunctivitis in adults and in children more than 2 years old.

Efficacy of anti-tumour necrosis factor-α monoclonal antibodies in patients with non-infectious anterior uveitis.

OBJECTIVES: To assess the efficacy of monoclonal anti-tumour necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors. METHODS: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analysed. RESULTS: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease-modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87). CONCLUSIONS: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilisation of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.

Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis.

Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease.

Inhibitory role of transforming growth factor ß2 in experimental autoimmune anterior uveitis.

PURPOSE: Experimental autoimmune anterior uveitis (EAAU) is a clinically relevant animal model for human idiopathic anterior uveitis (IAU). The role of the immunomodulator transforming growth factor ß2 (TGF-ß2) in EAAU pathology is unknown. In this study, we investigated the regulatory role of TGF-ß2 in EAAU. METHODS: EAAU was induced in male Lewis rats by footpad injection of melanin-associated antigen (MAA). TGF-ß2 was administered intravenously (iv) in MAA-sensitized rats during the induction of EAAU, or after the clinical onset of uveitis. MAA-sensitized rats injected similarly with an equal volume of PBS served as control. Animals were examined daily between days 7 and 30 post-injection for the clinical signs of uveitis using slit lamp biomicroscopy. Animals were sacrificed at various time points and eyes were harvested for histological analysis to assess the course and severity of inflammation. For histopathological analysis, paraffin sections of harvested eyes were stained with hematoxylin and eosin. Popliteal lymph nodes (LNs) were used for CD4+CD25+FoxP3+ T regulatory (Tregs) population analysis and for CD4+ T cell proliferation assay. RESULTS: Administration of recombinant TGF-ß2 during the early stages of EAAU prevented the induction of uveitis. Compared to PBS, the presence of TGF-ß2 in the cell culture significantly (p < 0.05) inhibited the proliferation of CD4+ T cells in response to MAA. In MAA-sensitized Lewis rats, iv treatment with recombinant TGF-ß2 resulted in significantly (p < 0.05) increased percentage of Tregs compared to animals treated similarly with PBS. Thus, TGF-ß2 inhibited the induction of EAAU by inhibiting CD4+ T cell proliferation and increasing the number of Tregs. Injection of TGF-ß2 in rats with active EAAU resulted in diminished disease activity. Unfortunately, this treatment did not lead to the early resolution of EAAU. CONCLUSIONS: TGF-ß2 plays a critical role in regulation of intraocular inflammation in EAAU. Findings reported in this study improve our understanding of immunopathology of IAU and suggest that recombinant TGF-ß2 may be a promising therapeutic agent for human IAU.

Anterior uveitis in patients with spondyloarthropathies in a single US academic center: a retrospective study.

Uveitis may represent an opportunity to diagnose spondyloarthropathies (SpA) earlier and influence treatment decisions. We describe the percentage of acute anterior uveitis (AAU) in a diverse group of SpA patients seen at one academic setting and compare demographic and clinical characteristics according to the presence of uveitis. We conducted a retrospective study of patients with SpA and AAU (January 2016-June 2017). Patients were identified using ICD-10 and administrative claim codes, diagnoses were confirmed through chart review. Extracted data included demographics, laboratory, clinical data, treatment and Routine Assessment of Patient Index Data 3 (RAPID3) scores based on Multidimensional Health Assessment Questionnaire (MDHAQ). Baseline description and comparison between the two groups were performed. We included 190 patients, mostly men (59.5%), with a mean age of 45.9 years: 48% with ankylosing spondylitis (AS), 26% with psoriatic arthritis (PsA), 22% with undifferentiated SpA, and 4% with SpA associated with inflammatory bowel disease (IBD). Uveitis was identified in 17% of patients, ranging from 25% in AS to 4% in PsA. Time from symptom onset to SpA diagnosis was longer in patients with uveitis (10.9 versus 5.9 years, p < 0.001). A higher percentage of patients with uveitis were HLA-B27 positive (85% versus 67%, p = 0.02). The prevalence of uveitis in our population was 17%, slightly lower than previously reported in the literature. There was a diagnostic delay of about 7 years, significantly longer in patients with uveitis. New screening strategies in collaboration with ophthalmology may lead to earlier diagnosis and better outcomes.

Immunohistochemical characterization of feline lymphoplasmacytic anterior uveitis.

OBJECTIVE: To characterize the immune cells present in different forms of feline anterior uveitis. SAMPLES: Eyes were obtained from 49 cats diagnosed with chronic idiopathic lymphoplasmacytic anterior uveitis, 7 cats with feline infectious peritonitis (FIP), and 9 cats euthanized for nonocular disease. METHODS: H&E sections were scored on the level of infiltrate in the anterior uvea. Immunohistochemistry was performed for FoxP3, CD3, and IL-17A, and positive cells were quantified in multiple images of each sample. A generalized estimating equation tested for an association between the level of inflammation and the prevalence of these cell types. RESULTS: Cells stained positive for IL-17A in idiopathic uveitis but not in FIP samples. We found significantly fewer FoxP3+ and CD3+ cells in low-grade compared with high-grade inflammation in idiopathic uveitis or FIP samples (P values all <.005), but no difference between FIP and high-grade samples. CONCLUSIONS: Idiopathic, but not FIP-associated, uveitis appears to have Th17 cell involvement. The numbers of FoxP3+ and CD3+ T-cells present appear directly correlated; thus, the severity of disease does not appear directly determined by the numbers of regulatory cells.

Peripheral blood monocytes reveal an activated phenotype in pediatric uveitis.

OBJECTIVE: To characterize peripheral blood monocytes in uveitis associated with juvenile idiopathic arthritis (JIAU). METHODS: Peripheral blood monocytes from children with JIA (either with (n = 18) or without uveitis (n = 11)), idiopathic anterior uveitis (IAU; n = 12) and healthy controls (n = 11) were analyzed by flow cytometry. RESULTS: Percentage of CD14 + CD86+ monocytes and CD86 expression on single cell level were significantly higher in all patient groups than in controls, whereas no major differences existed between patient groups. Frequency of CD39+ (p < 0.05 all groups) and CD73+ monocytes (p = 0.03 JIAU vs controls) was elevated in patients. Disease activity did not influence monocyte phenotypes, but in methotrexate-treated JIAU patients numbers of CCR2+ monocytes were reduced and numbers of CD86+ and CD39+ cells increased. CONCLUSION: Children with arthritis or uveitis display a distinct monocytic phenotype when compared to cells from healthy children. Phenotypic changes seem to be neither arthritis- nor uveitis-dependent, but may be modified by treatment.

The pathogenic role of dendritic cells in non-infectious anterior uveitis.

BACKGROUND: Anterior uveitis (AU) is characterised by infiltration of immune cells into the anterior chamber of the eye. Dendritic cells (DC) are professional antigen presenting cells that initiate and promote inflammation. This study aims to characterise DC in AU and to examine the effects of aqueous humor (AqH) on DC maturation and function. METHODS: The frequency and phenotype of AU and healthy control (HC) circulating DC was examined. AU and HC AqH was immunostained and assessed by flow cytometry. The effect of AU and HC AqH on DC activation and maturation was examined and subsequent effects on CD4+ T cell proliferation assessed. RESULTS: AU peripheral blood demonstrated decreased circulating myeloid and plasmacytoid DC. Within AU AqH, three populations of CD45+ cells were significantly enriched compared to HC; DCs (CD11c+ HLA-DR+), neutrophils (CD15+ CD11c+) and T cells (CD4+ and CD8+). A significant increase in IFNγ, IL8 and IL6 was observed in the AU AqH, which was also significantly higher than that of paired serum. AU AqH induced expression of CD40 and CD80 on DC, which resulted in increased T cell proliferation and the production of GM-CSF, IFNγ and TNFα. CONCLUSION: DC are enriched at the site of inflammation in AU. Our data demonstrate an increase in inflammatory mediators in the AU inflamed microenvironment. AU AqH can activate DC, leading to subsequent proliferation and activation of effector T cells. Thus, the AU microenvironment contributes to immune cell responses and intraocular inflammation.

Ocular features of the HLA-B27-positive seronegative spondyloarthropathies.

PURPOSE OF REVIEW: The seronegative spondyloarthropathies are a closely related group of inflammatory diseases that include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, inflammatory bowel disease and undifferentiated spondyloarthritis. This review focuses on the spectrum of ocular manifestations associated with these diseases and the current approaches in treating these ocular manifestations. It also highlights the role ophthalmologists can play in identifying and appropriately treating human leukocyte antigen B27 (HLA-B27) associated uveitis and the associated spondyloarthropathies in order to limit ocular and systemic morbidity. RECENT FINDINGS: Evolving treatment paradigms for the seronegative spondyloarthropathies should direct the choice in therapeutic agent for difficult to control associated uveitis. Biologic therapies, particularly tumor necrosis factor inhibitors, are playing an increasing role in the treatment. SUMMARY: Acute anterior uveitis is the most common ocular manifestation in HLA-B27 positive seronegative spondyloarthropathies. Suspicion for HLA-B27 associated uveitis should prompt a careful clinical history and rheumatologic referral if symptoms of an inflammatory arthropathy are present. Therapy is tailored based on severity of ocular and systemic manifestations with interventions from topical corticosteroids to immunomodulating agents available in treating these diseases.

Potential predictors for frequent relapse in human leukocyte antigen-B27-associated uveitis.

PURPOSE: To identify potential predictors for frequent relapse in a cohort of patients with human leukocyte antigen (HLA)-B27-associated uveitis in a tertiary referral center at the initial visit. METHODS: This retrospective cohort study comprised 130 patients diagnosed with HLA-B27-associated uveitis. Subjects were divided into two groups according to the frequency of uveitis attacks (number/year): frequent relapse (FR) (who relapsed more than twice a year, 38) and infrequent relapse (IR) group (who relapsed twice or less than twice a year, 92). RESULTS: The FR group presented more often with hypopyon or posterior synechiae at the initial presentation. Interestingly, posterior segment involvements including vitritis, vasculitis, or cystoid macular edema were not significantly different between the groups. In terms of laboratory findings, the erythrocyte sedimentation rate (ESR) was higher in the FR group. Multivariate Cox hazards analysis showed male sex, the presence of hypopyon, and ESR to be potential predictive factors for frequent relapse. CONCLUSION: We found that male sex, hypopyon at presentation, and high ESR are potential predictors for frequent relapse in HLA-B27-associated uveitis. Identifying patients at higher risk of relapse could provide important information for patients, allowing patients to understand their condition and increase their acceptance of strict management.

The effect of methotrexate and sulfasalazine on the course of HLA-B27-positive anterior uveitis: results from a retrospective cohort study.

PURPOSE: To investigate the effect of methotrexate (MTX) or sulfasalazine (SSZ) on the course of HLA-B27-positive, remitting acute anterior uveitis (AAU). METHODS: Forty-six patients with HLA-B27-positive AAU with or without associated systemic rheumatic disease either receiving MTX (n = 20), SSZ (n = 13), or no systemic immunomodulating treatment (Ctrl; n = 13) were studied retrospectively. Best-corrected visual acuity (BCVA), AAU relapse rate, and occurrence of uveitis-related ocular complications were analyzed at baseline (BL) and at 12-month follow-up (FU). RESULTS: Groups did not differ regarding age, gender, and presence of associated systemic diseases. BCVA at baseline was significantly worse in patients receiving MTX (logMAR 0.39 ± 0.4) than in those treated with SSZ (0.17 ± 0.2; P = 0.05) or in controls (Ctrl; 0.14 ± 0.2; P = 0.009). At the 12-month endpoint, MTX treatment was associated with significantly improved BCVA (0.18 ± 0.4 logMAR; P = 0.004). In contrast, BCVA did not significantly change in patients treated with SSZ (0.17 ± 0.3 logMAR) or in the controls (0.11 ± 0.2 logMAR). The annual uveitis relapse rate significantly decreased with MTX (BL 3.6 ± 2.4 relapses to FU 0.7 ± 0.8; P = 0.0001) and SSZ (BL 3.6 ± 1.9 to FU 1.8 ± 2.4, P < 0.01), but not in the controls (BL 1.9 ± 1.4 vs 1.9 ± 1.7 FU). The complication rate was slightly reduced with MTX (BL 1.75 ± 1.2 complications present versus FU 1.3 ± 1.2, P = 0.09) but not with SSZ (BL 0.9 ± 0.8 to FU 1.3 ± 1.4; P = 0.4) or in the controls (BL and FU 1.0 ± 0.95; P = 0.7). CONCLUSIONS: MTX and SSZ reduced the uveitis relapse rate in HLA-B27-positive AAU patients, with MTX showing a beneficial effect on AAU-related macular edema.

New developments in uveitis associated with HLA B27.

PURPOSE OF REVIEW: Uveitis is the most common, clinically apparent, extra-articular manifestation of axial spondyloarthritis. This review summarizes recent publications related to this form of uveitis. RECENT FINDINGS: Studies published since the start of 2015 address the worldwide prevalence of human leukocyte antigen (HLA) B27-associated uveitis, the prevalence of axial spondyloarthritis among patients with B27-associated acute anterior uveitis (AAU), the genetics of AAU and some of the clinical implications of AAU. Progress has been made in the treatment of uveitis in general and in the treatment of uveitis in association with spondyloarthropathy in particular. The pathogenesis of AAU might derive clues from the above as well as from an understanding of the microbiome and possibly from knowledge derived from uveitis in association with Ebola. SUMMARY: Although HLA B27-associated uveitis has been recognized since 1973, a variety of recent observations shed new light on this common clinical association with spondyloarthritis.

MicroRNA-146a Alleviates Experimental Autoimmune Anterior Uveitis in the Eyes of Lewis Rats.

PURPOSE: This study aimed to determine the effect and roles of microRNA (miRNA, miR) treatment in experimental autoimmune anterior uveitis (EAAU). MATERIALS AND METHODS: Uveitis was induced in Lewis rats by simultaneous injections of bovine melanin-associated antigen into the hind footpad and the intraperitoneal cavity. The animals were injected intravitreally with low-dose (0.5 µg) or high-dose (1.5 µg) miR-146a. The clinical scores, leukocyte count in the aqueous humor, and histology were assessed. Cytokine changes were evaluated by relative mRNA expression and enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF-κB was performed by electrophoretic mobility shift assay (EMSA). RESULTS: Treatment with miR-146a significantly attenuated clinical scores and leukocyte infiltration in a dose-dependent manner, a result that was compatible with histological findings. Following miR-146a injections, downregulation of interleukin- (IL-) 1ß, IL-6, and IL-12 and interferon- (IFN-) γ and upregulation of IL-10 and IL-17 were noted. The decreased NF-κB expression on immunofluorescence and Western blotting and reduced DNA-binding activity on EMSA were demonstrated following miR-146a treatment. CONCLUSIONS: miR-146a effectively reduced intraocular inflammation in EAAU through the inhibition of NF-κB. miR-146a might be a new treatment choice for uveitis.

[HLA-B27 Positive Acute Anterior Uveitis - A Translational Perspective]. / HLA-B27-positive akute anteriore Uveitis ­ eine translationale Perspektive.

Background HLA-B27 positive acute anterior uveitis is the most common type of uveitis, and it is an autoimmune disease that can be triggered by infections. The precise mechanism of the interaction between involved microbes (mostly gram negative bacteria) and the host immune system is not clear. The disease probably results from an imbalance between pro- and anti-inflammatory components. Project description This article gives a compact overview about the current knowledge of the clinic and the etiopathogenesis of acute anterior uveitis as a basis for future research approaches. The goal of the current research is to classify the cellular and molecular pathogenetic factors in acute anterior uveitis. In this regard, a project on uveitis within the clinical research unit FOR 2240 "(Lymph)Angiogenesis and Cellular Immunity in Inflammatory Diseases of the Eye", examines the hypothesis that dysregulation of regulatory cell populations and anti-inflammatory cytokines, such as interleukin-10 (IL-10), might contribute to the development of ocular autoimmunity following infections. The goal is to establish new markers for individual susceptibility in the risk group of the HLA-B27 positive population, because only about 1% of the HLA-B27 positive population will eventually develop acute anterior uveitis. Conclusions Translational research approaches to identify predisposed risk groups from the HLA-B27 population could improve patient care both on a prophylactic and a therapeutic level.

Description and Prevalence of Spondyloarthritis in Patients with Anterior Uveitis: The SENTINEL Interdisciplinary Collaborative Project.

PURPOSE: To describe and analyze the prevalence of spondyloarthritis (SpA) in patients with anterior uveitis (AU). DESIGN: Multicentric, observational, prospective study. PARTICIPANTS: Consecutive patients with AU who were human leukocyte antigen (HLA)-B27 positive or HLA-B27 negative with more than 1 episode of AU separated by at least 3 months were selected. Patients with a previous diagnosis of SpA were excluded. METHODS: Included patients were evaluated by an ophthalmologist and a rheumatologist following a predefined visit schedule. MAIN OUTCOME MEASURES: Sociodemographic and clinical variables including the diagnosis of SpA according to Assessment of SpondyloArthritis International Society (ASAS) criteria and an exhaustive ophthalmological examination (best-corrected visual acuity, intraocular pressure, biomicroscopic examination of the anterior and posterior segment of the eye, cataract evaluation, optical coherence tomography evaluating both the 1-mm central retina thickness and the optic nerve head and retinal nerve fiber layer, and visual field in a dark room with 1 eye patched) were collected. Baseline descriptive, bivariate, and concordance analyses were performed. RESULTS: We included 798 patients, mostly men (59%) with a mean age of 45 years; 60% were AU HLA-B27 positive, and 40% had recurrent negative AU HLA-B27. A total of 50.2% and 17.5% of patients presented axial and peripheral SpA according to ASAS criteria, respectively. Patients with AU who were HLA-B27 positive were more frequently diagnosed with axial (69.8% vs. 27.3%, P < 0.0001) and peripheral SpA (21.9% vs. 11.1%, P < 0.0001) than patients with recurrent negative AU HLA-B27. In general, we did not detect important differences between groups in the ophthalmologic variables. CONCLUSIONS: A large percentage of patients with clinically significant AU have an undiagnosed SpA. This percentage is even higher if the HLA-B27 haplotype is positive.

Expression of MicroRNAs in the Eyes of Lewis Rats with Experimental Autoimmune Anterior Uveitis.

Purpose. This study aimed to determine the dynamic changes of NF-κB-related microRNAs (miRNAs) and cytokines over the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis. Materials and Methods. Uveitis was induced in Lewis rats using bovine melanin-associated antigen. The inflammatory activity of the anterior chamber was clinically scored, and leukocytes in the aqueous humor were quantified. RNA was extracted from the iris/ciliary bodies and popliteal lymph nodes to reveal the dynamic changes of eight target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and six cytokine mRNAs (IFN-γ, IL-17, IL-12A, IL-1ß, IL-6, and IL-10). In situ hybridization of miRNA and enzyme-linked immunosorbent assay quantification of cytokines were performed to confirm the results. Results. Disease activity and leukocyte quantification were maximum at day 15 after immunization. The profiling of miRNA revealed downregulation of miR-146a-5p, miR-155-5p, miR-223-3p, and miR-147b and upregulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokine analysis revealed IFN-γ, IL-17, IL-12A, IL-1ß, and IL-6 overexpression, with IL-10 downregulation. Conclusions. Dynamic changes of miRNAs were observed over the course of EAAU. By initiating NF-κB signaling, the expressions of downstream cytokines and effector cells from the Th17 and Th1 lineages were sequentially activated, contributing to the disease.

Systemic sclerosis sine scleroderma: a case report of anterior uveitis.

Systemic sclerosis (SSc) sine scleroderma (ssSSc) is characterized by the absence of skin involvement, despite other manifestations of systemic sclerosis are present. It is not known whether sSSc represents a forme fruste of limited cutaneous SSc or a distinct entity, but the 2013 American College of Rheumatology/European League Against Rheumatism criteria for the classification of SSc have considered SSc without skin involvement to be a distinct subset. The authors present the case of a 70-year old female that was referred for a consultation for Raynaud's phenomenon and a chronic anterior uveitis (CAU). She had a history of dysphagia, diffuse pulmonary emphysema and a biopsy-documented fibrosis of the upper lobes, and an idiopathic non-ischemic dilated cardiomyopathy with severe left ventricle systolic dysfunction and left bundle branch block. Anti-nuclear and anti-centromere antibodies were positive, while manometry revealed distal esophageal hypomotility. After establishing the diagnosis of ssSSc and starting immunosuppression, the ocular disease improved, while the lung and heart diseases remained stable. This case underlines that it is very important to suspect SSc when CAU is present and/or skin thickening is absent. To our knowledge, this is the first report of CAU in a patient with ssSSc.