Preliminary Report on Interleukin-22, GM-CSF, and IL-17F in the Pathogenesis of Acute Anterior Uveitis.

Purpose:Anterior uveitis is the most common anatomic subset of uveitis. We developed a novel multi-parametric flow cytometry panel to identify immune dysregulation signatures in HLA B27-associated acute anterior uveitis (AAU) and axial spondyloarthritis (AxSpA).Methods: We used fluorescence activated cell sorting to characterize T cell cytokine expression in stimulated T cell subsets from patients with AAU (n = 4) compared to healthy controls (n = 14) or subjects with AxSpA (n = 6).Results: Positive findings among subjects with AAU included a statistically significant increase in stimulated granulocyte-macrophage colony stimulating factor (GM-CSF), IL-17, and IL-22 synthesized by CD8 cells, a trend for stimulated ILC (innate lymphoid cells)-3 cells to synthesize more IL-22 (p = .07), and stimulated MAIT (mucosa associated innate lymphoid cells)-like cells that express the T cell receptor V alpha 7.2 to express IL-17A, IL-17F, and IL-22 in a greater percentage of cells relative to controls. IL-17F, GM- CSF, and IL-22 represent potentially novel targets in AAU.Conclusion: Our report is arguably the first to implicate IL-17F or ILC-3 and MAIT cells in the pathogenesis of AAU.Abbreviations AAU: acute anterior uveitis; AxSpA: axial spondyloarthritis; BASDAI: Bath ankylosing spondylitis disease activity index; CCR: chemokine receptor; DMSO: dimethylsulfoxide; EULAR:European League Against Rheumatism; FACS: fluorescence activated cell sorter; FBS: fetal bovine serum; FSC: orward light scatter; GM-CSF: granulocyte-macrophage colony stimulating factor; HC: healthy control; ILC: innate lymphoid cell; KIR: killer immunoglobulin receptor; MAIT: mucosal associated immune T cell; ND: not detected; NK: natural killer cell; OHSU-Oregon Health & Science University; PBMC: peripheral blood mononuclear cell; SSC: side light scatter; TCR: T cell receptor.

Increased Circulating Proinflammatory T Lymphocytes in Children with Different Forms of Anterior Uveitis: Results from a Pilot Study.

Purpose: To characterize peripheral blood T cells in juvenile idiopathic arthritis-associated uveitis (JIAU). Methods: Blood samples were taken from children with JIAU (n = 18), JIA without ocular involvement (n = 11), idiopathic anterior uveitis (IAU, n = 12), and healthy controls (n = 11). Cells were stained for T cell surface markers, and intracellular cytokine staining was performed after cell stimulation and analyzed by flow cytometry. Results: The Th1/Th2 ratio was increased in JIAU patients. Numbers of IL-13-expressing cells an level of IL-13 and IL-10 expression per cell were increased in all patient groups; whereas, percentages of IL-5-expressing T cells were decreased. Numbers of proinflammatory Th17 cells and T cells expressing CTLA-4 were increased in all patient groups; whereas, γ/δ T cell numbers were decreased. Results from JIA and IAU were similar. Conclusion: T cell subtypes and potential T cell function are altered in pediatric patients with uveitis and arthritis as compared to healthy children.

The Expression of Calprotectin and Factors in TLR4/NF-κB/MyD88 Pathway in Patients with Idiopathic Acute Anterior Uveitis.

Purpose: The purpose of the article is to investigate the contribution of calprotectin and factors in toll-like receptor 4/nuclear factor-κB/myeloid differentiation factor 88 (TLR4/NF-κB/MyD88) pathway in patients with idiopathic acute anterior uveitis (IAAU). Methods: In total, 72 patients with IAAU and 56 healthy individuals were enrolled. Serum calprotectin, TLR-4, and MyD88 were determined. Best-corrected visual acuity, uveitis activity grading, and macular thickness measured by optical coherence tomography were performed. Results: Serum calprotectin, TLR4, and MyD88 levels were higher in IAAU group than those in healthy individuals. Serum calprotectin level was positively correlated with uveitis activity grading and macular thickness. Receiver operating characteristic curve analysis showed serum calprotectin had larger area under curve than serum TLR4 and MyD88. Conclusions: The calprotectin and TLR4/NF-κB/MyD88 signal might contribute to the pathogenesis of IAAU and serum calprotectin might be a specific biomarker for the measurement of ocular inflammation in IAAU.

Elevated Interleukin 37 Expression Associated With Disease Activity in HLA-B27 Associated Anterior Uveitis and Idiopathic Anterior Uveitis.

BACKGROUND & OBJECTIVE: Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS: 15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016. Complete ophthalmological examinations were performed and clinical features were clearly documented. Blood samples were collected and peripheral blood mononuclear cells were extracted. IL-37 messenger RNA (mRNA) and protein expression in peripheral blood mononuclear cells (PBMCs) were examined by performing RT-PCRs and western blot, respectively. Cytokines in the supernatants of stimulated dendritic cells (DCs) with IL-37 were assayed by multiplex immunoassay. RESULTS: An increased level of IL-37 mRNA and protein expression by PBMCs was found in the patient group with clinically active AAU compared to controls. There was no significant difference in IL-37 mRNA and protein expression levels between HLA-B27 associated AAU and idiopathic AAU. IL-37 significantly inhibited the production of IL-1ß, IL-6, IL-10, IL-21, IL-23, TNF-α and IFN-γ. IL-37 levels of mRNA and protein expression showed a significant positive correlation with disease activity. CONCLUSIONS: Elevated IL-37 expression is associated with disease activity in HLA-B27 associated AAU and idiopathic AAU. IL-37 can inhibit proinflammatory cytokine productions in AAU. Manipulation of IL-37 may offer a new therapeutic target for these entities.

Association of IL33 and IL1RAP Polymorphisms With Acute Anterior Uveitis.

BACKGROUND: AAU (acute anterior uveitis) is the most common entity of uveitis characterized by acute vision loss and violent sore eyes. IL-33 and IL-1RacP have been found to play crucial roles in the innate immune system. OBJECTIVE: In the present study, we investigated the association of IL33 and IL1RAP genes with AAU. METHOD: A total of 549 AAU patients and 1080 unrelated healthy controls were recruited for this study. Ten single nucleotide polymorphisms (SNPs) were genotyped using Sequenom Mass ARRAY technology. RESULTS: Our findings demonstrated that IL1RAP-rs3773978 significantly associated with AAU and could serve as a genetic risk marker in Chinese AAU patients. A significantly increased frequency of the A allele and AA homozygosity of IL1RAP-rs3773978 was observed in AAU patients compared with that in controls (p=0.001, pc=0.01, OR=1.282, 95% CI 1.106 to 1.487; p=0.0003, pc=0.003, OR=1.647, 95% CI 1.255 to 2.163, respectively). Further stratification analyses showed that the genetic correlation may differ depending on HLA-B27 status, AS (ankylosing spondylitis) status, attack times and laterality status. CONCLUSION: Our findings provide new insights that enhance the current knowledge of uveitis genetics by demonstrating the specific functional roles of IL1RAP and other IL-1 family genes in uveitis.

Could be serum uric acid a risk factor for thrombosis and/or uveitis in Behcet's disease?

Introduction Serum uric acid level increases in many inflammatory conditions. Uric acid triggers the vascular inflammation and artery damage, which causes to an increased risk of endothelial dysfunction and atherosclerosis. It is not clear in the literature whether uric acid contributes to uveitis by similar mechanisms. We investigated whether uric acid level increases in Behcet's disease patients with thrombosis or anterior uveitis. Patients and methods We reviewed the medical records of 914 Behcet's disease. After screening for exclusion criteria, there were 50 Behcet's disease patients with thrombotic complication and as the control group 202 BD patients without any vascular complication were included to the study. In the Anterior uveitis group, there were 53 Behcet's disease patients. The Control group consisted of 39 Behçet's disease patients without eye findings. Results Mean uric acid value was 4.96 ± 1.06 mg/dl in Behcet's disease patients with thrombosis whereas 4.08 ± 0.94 mg/dl in controls, indicating a significant difference ( p < 0.001). There was no significant difference between the mean ages of the patients in both groups. The mean age of the BD group without eye findings was 39.31 ± 10.47 years and that of the Behcet's disease with Anterior Uveitis group was 37.72 ± 9.65 years ( p = 0.453). The mean serum UA in the BD group without eye findings was 4.21 ± 1.21 mg/dl, while in the BD with Anterior Uveitis group it was 4.57 ± 1.37 mg/dl ( p = 0.201). Conclusion The extent of increase in uric acid level was greater in Behcet's disease patients that have a thrombotic complication compared to those without thrombotic complication. Uric acid seems to play a role in the pathogenesis of thrombosis. It is concluded that the elevation of serum uric acid level in patients with anterior uveitis with Behcet's disease is not statistically significant.

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.

Comparison of the Diagnostic Power of Serum IL-6, IL-8 and TNF-α for the Idiopathic Anterior Uveitis in Children.

BACKGROUND: Uveitis is the inflammation of the uvea that often occurs in children. There are many causes of disease, but some of them do not have any reasons and are then called idiopathic uveitis. Cytokines play an important role in the regulation of the immune response. Determination of cytokine profiles could contribute to the explanation of the etiology of uveitis and could serve to evaluate the inflammation intensity as well as be helpful in the early diagnosis this disease. The purpose of this study was to determine the serum level of selected inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α) and to compare their diagnostic power as a markers of idiopathic anterior uveitis in children. METHODS: The study was carried out on 28 children diagnosed with idiopathic anterior uveitis. The reference group comprised 30 healthy children. Serum IL-6, IL-8, and TNF-α concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods. RESULTS: The mean values of IL-6, IL-8, and TNF-α in the children with idiopathic anterior uveitis were significantly higher than those found in the reference group. The highest sensitivity, specificity, accuracy, positive and negative predictive value, and likelihood ratio of a positive test result were achieved for IL-8. There was a significant difference between the area under the curve for IL-6 and IL-8. CONCLUSIONS: Increased serum concentrations of interleukin IL-6, IL-8, and TNF-α may suggest that these cytokines induce inflammatory changes in the ocular surface. Analysis of cytokine levels showed that IL-8 has the highest diagnostic power and is the best marker for diagnosis of idiopathic anterior uveitis in children.

Anticentromere antibody positive Ackerman's Syndrome with Granulomatous Anterior Uveitis.

Ackerman's Syndrome or Intersticial Granulomatous Dermatitis with Arthritis has been an issue of increasing number of reports in the last decade which had focused its heterogeneous cutaneous and rheumatologic expression besides the initial manifestations reported by Ackerman and his group. Granulomatosis anterior uveitis has not been previously described. Some patients are reported to have positive autoantibodies but association with anticentromere antibodies has not been previously described as well, to our knowledge. We report a new case of Ackerman Syndrome with cutaneous, articular and ocular involvement with positive anticentromere antibodies successfully treated with systemic steroids, methotrexate, hydroxychloroquine and cyclosporine. The ocular involvement and the association of anticentromere antibodies lead us to hypothesize that constellation of symptoms and autoimmune mechanisms of this uncommon multisystemic syndrome are yet to be clarified.

Imbalance of Th17/Treg cells in pathogenesis of patients with human leukocyte antigen B27 associated acute anterior uveitis.

Th17 and regulatory T cells, involved in the pathogenesis of several autoimmune diseases, are new lineages of CD4+ T helper cells. However, the role of their imbalance in human leukocyte antigen B27-associated acute anterior uveitis has not been elucidated. In our study, the percentages of Th17 and Treg cells, their molecular markers and related factors in peripheral blood of patients and healthy controls were measured by flow cytometry, real-time RT-PCR and ELISA. We observed a remarkable increase of CD4+ and CD4+IL-17+ T cells in peripheral blood of patients compared to controls. The molecular markers and related factors of Th17 cell were also showed a distinct elevation. Interestingly, we observed an obvious decrease of CD4+CD25+Foxp3+ T cells and Foxp3 mRNA level in patients. The ratio of Th17/Treg in patients was dramatically higher than controls. Moreover, the ratio of Th17/Treg cells had a more significantly positive correlation with the disease activity score than Th17 cells whereas Treg cells had a negative correlation. Our findings demonstrated a distinct increase of Th17 cells and a significant decrease of Treg cells in patients compared to controls. The imbalance of Th17 and Treg cells may play a vital role in the pathogenesis of the disease.

Serum Vitamin D Levels in Patients with Acute Anterior Uveitis.

PURPOSE: To evaluate serum 25-hydroxyvitamin D levels in patients with acute anterior uveitis (AAU). METHODS: This observational case-control study involved 20 patients with AAU, and 20 consecutive, age and sex-matched healthy subjects without any ocular or systemic diseases. Serum 25-hydroxyvitamin D was quantified with electrochemiluminescence technique. RESULTS: No significant differences were found between the groups with respect to age (p = 0.185) and sex (p = 0.465). Serum vitamin D levels of the subjects with AAU (mean 5.75 ± 4.50 ng/mL, median 4.00 ng/mL, range: 3.00-19.00 ng/mL) were significantly lower than the control group (mean 12.96 ± 5.89 ng/mL, median 11.00 ng/mL, range: 5.20-25.92 ng/mL) (p<0.001). CONCLUSIONS: We found significantly low serum levels of vitamin D in patients with AAU, which suggest that vitamin D deficiency may play a role in the pathogenesis of anterior uveitis. Further studies are necessary to demonstrate the efficacy of vitamin D supplementation in the management of patients with anterior uveitis.

Association of Low Vitamin D Levels With Noninfectious Anterior Uveitis.

Importance: Vitamin D plays an important role in both the innate and adaptive immune systems. It has been shown to contribute to the etiology of T-cell-mediated autoimmune diseases through the upregulation of type 2 anti-inflammatory T helper cells and the suppression of type 1 T helper cells. Noninfectious uveitis is postulated to be caused by immune dysfunction. Objective: To determine whether there is an association between vitamin D levels and noninfectious anterior uveitis. Design, Setting, and Participants: This was a case-control study. We identified patients with and without noninfectious uveitis using the Massachusetts Eye and Ear Infirmary Ocular Inflammation Database and electronic medical records from March 1, 2008, to December 12, 2015, at the Massachusetts Eye and Ear Infirmary Uveitis and Comprehensive Ophthalmology Clinics. One hundred patients with noninfectious anterior uveitis and 100 patients without uveitis were recruited. Patients with noninfectious uveitis were diagnosed by fellowship-trained uveitis specialists after exclusion of infectious causes and neoplastic masquerades of uveitis. All patients included had a total 25-hydroxyvitamin D level recorded. Multivariate regression models were constructed to determine the association between vitamin D levels and the presence of uveitis. Main Outcome and Measure: Presence of noninfectious anterior uveitis. Results: We identified 100 patients (64 white, 8 African American, 25 Asian, and 3 Hispanic) with a mean (SD) age of 51.8 (15.9) years (26 men) and 100 control individuals (58 white, 23 African American, 8 Asian, and 11 Hispanic) with a mean (SD) age of 53.6 (16.2) years (27 men). Hypovitaminosis D was associated with noninfectious uveitis in the univariate analysis (odds ratio, 2.53; 95% CI, 1.42-4.51; P = .002). The association in multivariate regression after adjusting for age, sex, and race/ethnicity was 2.96 (95% CI, 1.60-5.50; P = .001) The odds of developing uveitis were 4% lower for every 1-ng/mL increase in vitamin D level (odds ratio, 0.96; 95% CI, 0.93-0.99; P = .01) in the main multivariate analysis. Conclusions and Relevance: In this retrospective study, lower vitamin D levels were associated with an increased risk of noninfectious anterior uveitis. However, this does not confirm a causal effect.

The role of Vitamin D in immuno-inflammatory responses in Ankylosing Spondylitis patients with and without Acute Anterior Uveitis.

Hypothesis:Abnormal Vitamin D (Vit D) level could have consequences on the immuno-inflammatory processes in Ankylosing Spondylitis (AS). Aim:The purpose of this study was to analyze the role of Vitamin D in the interplay between immune and inflammation effectors in AS associated-Acute Anterior Uveitis (AAU). Methods and Results:25-hydroxyvitamin D (Vit D), LL-37 peptide, IL-8 and Serum Amyloid A (SAA) were identified and quantified in the serum/ plasma of thirty-four AS patients [eleven AS patients presenting AAU (AAU AS patients) and twenty-three AS patients without AAU (wAAU AS patients)] and eighteen healthy individuals (Control) using enzyme-linked immunosorbent assay. Acute-phase SAA level was significantly higher in AS patients compared to Controls. Contrary with wAAU AS patients, significantly elevated levels of IL-8, and diminished levels of Vit D characterized AAU AS patients. Regarding LL-37, its level decreased concomitantly with the level of Vit D. When AS patients were subgrouped based on AAU presence or on Vit D level, important associations between immuno-inflammatory assessed markers and AS features were noticed. Generally, Vit D levels were associated indirectly with leukocytes/ neutrophils number or with ESR, CRP, and Fibrinogen levels. The levels of SAA and IL-8 associated directly with AAU or with AAU relapses, especially in AS patients with Vit D insufficiency, while SAA associated directly with infection/ inflammatory markers and with disease activity indexes or with the degree of functional limitation. Discussion:Altered levels of Vit D affect the balance between LL-37, IL-8 and SAA, suggesting an association with AAU, an extra-articular manifestation of AS. Abbreviations:Vit D = Vitamin D, AS = Ankylosing Spondylitis, AAU = Acute Anterior Uveitis, AAU AS = AS patients with AAU, wAAU AS = AS patients without AAU, SSZ = Sulphasalazine, Leu = Leukocytes, Neu = Neutrophils.

Extra-Articular Symptoms in Constellation with Selected Serum Cytokines and Disease Activity in Spondyloarthritis.

Objectives. In this study, we assessed the extra-articular symptoms in constellation with selected serum cytokines and disease activity in spondyloarthritis (SpA). Patients and Methods. We studied 287 SpA patients: 131 had AS, 110 had PsA, and 46 had SAPHO. We assessed extra-articular symptoms in all cases. In 191 SpA patients, we measured serum interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-23 (IL-23), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). Results. Patients with acute anterior uveitis (AAU) had higher VAS (P = 0.0008), BADSDAI (P = 0.0001), ASDAS-ESR (P = 0.04), CRP (P = 0.006), IL-6 (P = 0.02), and IL-18 (P = 0.03) levels. Patients with inflammatory bowel disease (IBD) had higher VAS (P = 0.03), CRP (P = 0.0009), and IL-6 (P = 0.0003) levels. Patients with skin psoriasis had lower VAS (P = 0.001) and BASDAI (P = 0.00007) levels. Patients with psoriatic onycholysis had lower VAS (P = 0.006), BASDAI (P = 0.00001), and CRP (P = 0.02) and higher IL-23 (P = 0.04) levels. Patients with PPP had lower BASDAI (P = 0.04) and higher ET-1 (P = 0.001) levels. Conclusions. SpA patients with increased serum IL-18 and decreased serum ET-1 had an increased risk of extra-articular symptoms. In SpA patients, increased disease activity was associated with an increased risk of AAU and IBD and a decreased risk of skin psoriasis, psoriatic onycholysis, and PPP.

Presence of HLA-B27 is associated with changes of serum levels of mediators of the Wnt and hedgehog pathway.

BACKGROUND: HLA-B27 is present in 5% of the Caucasian population and is strongly associated with the development of spondyloarthritis (SpA), a disease characterized by inflammation and substantial bone changes. We hypothesized that the presence of HLA-B27 in itself is associated with alterations of key regulatory of bone homeostasis. METHODS: Sera of 241 individuals were assessed for the serum levels of Wnt pathway regulators, sclerostin and dickkopf (Dkk)-1 as well as Indian hedgehog (IHH) and collagen type I cleavage products (CTX1). Of the 151 HLA-B27+ subjects, 31 had SpA, 30 had anterior uveitis, 30 were healthy individuals and 60 healthy siblings of patients with SpA. RESULTS: Sclerostin levels were significantly (P<0.001) lower in HLA-B27+ subjects (314±21pg/mL) compared to HLA-B27 negative controls (mean±SEM: 492±30pg/mL), no matter if subjects were either healthy, or affected by SpA or uveitis. Similar results were found for Dkk-1. No differences between the groups with respect to the bone resorption marker CTX1 were found. In contrast, IHH levels were significantly (P<0.001) higher in the carriers of HLA-B27 than in the negative controls. CONCLUSIONS: Changes in key regulators of the Wnt pathway as well as IHH, a molecule regulating endochondral ossification, are found in HLA-B27 carriers, independent if they were healthy or affected by uveitis or SpA.

Elevated S100A8/A9 and S100A12 Serum Levels Reflect Intraocular Inflammation in Juvenile Idiopathic Arthritis-Associated Uveitis: Results From a Pilot Study.

PURPOSE: Juvenile idiopathic arthritis-associated uveitis (JIAU) is the most common uveitis entity in childhood. As S100A8/A9 and S100A12 proteins are valuable biomarkers in childhood arthritis, we investigated the occurrence of these proteins in childhood uveitis. METHODS: Serum samples from patients with JIAU (n = 79) or idiopathic anterior uveitis (IAU, n = 24), as well as from nonuveitic controls (n = 24), were collected. Furthermore, aqueous humor samples (JIAU n = 17, nonuveitic controls n = 16, IAU n = 12) were obtained. Samples were analyzed for S100A8/A9 and S100A12 protein levels by ELISA. Intergroup comparisons were performed, involving patient data, clinical data, and S100 levels. RESULTS: S100A8/A9 and S100A12 serum levels were elevated in IAU and JIAU patients as compared to nonuveitic controls (all P < 0.05). S100 serum levels in JIAU patients were higher in active arthritis (not significant; P = 0.289 for S100A8/A9 and P = 0.196 for S100A12) and active uveitis (P = 0.010 for S100A8/A9 and P = 0.026 for S100A12) than in controls. No significant differences in S100 levels were found in a subgroup analysis for sex, antinuclear antibody (ANA) status, disease duration, or presence of uveitis complications. In JIAU patients, S100 serum levels correlated with age and age at onset of uveitis. A longitudinal analysis in JIAU patients showed a correlation of serum S100A8/A9 and S100A12 levels with uveitis activity (both P = 0.03). S100A8/A9 levels in aqueous humor of patients with JIAU (P = 0.001) and IAU (P = 0.0002) were increased as compared to nonuveitic controls. CONCLUSIONS: Increased S100A8/A9 and S100A12 levels are found in the serum and aqueous humor of patients with autoimmune uveitis. Serum levels reflect activity of joint and eye disease.

Cytokine Expression Profile in Aqueous Humor and Sera of Patients with Acute Anterior Uveitis.

PURPOSE: To evaluate cytokine expression profile in aqueous humor and sera in patients with HLAB27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS: Twenty patients with AAU and 17 controls were recruited from August 2012 to March 2013. Study subjects with uveitis were divided into two groups: 9 patients with idiopathic AAU and 11 patients with HLA-B27 associated AAU. Complete ophthalmological examinations were performed and clinical features of each group were clearly documented. Aqueous humor and sera were collected and the concentration of 15 immune mediators (IL-1ß, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, TNF-α, IFN-γ, sCD40L) were measured in both aqueous humor and sera simultaneously by multiplex immunoassay. RESULTS: There were significantly higher levels of multiple cytokines in aqueous humor in patients with uveitis compared to controls, including IL-1ß, IL-6, IL-10, IL-17a, IL-17f, IL-21, IL-25, IL-31, IFN-γ, TNF-α, and sCD40L. The levels of IL-17a in aqueous humor correlated significantly with disease activity in patients with idiopathic AAU, while the level of IFN-γ in aqueous humor correlated significantly with disease activity in patients with HLA-B27 associated AAU. There was no significant difference in serum cytokine expression between uveitis patients and controls except IL-6, elevated in patients with both idiopathic and HLA-B27 associated AAU. CONCLUSION: Cytokine expression pattern in the aqueous humor, in contrast to that in serum, may reflect intraocular immune reactions during active inflammation in patients with AAU. Both Th1 and Th17 are involved in immunopathogenesis of HLA-B27 associated and idiopathic AAU, but a different cytokine pattern was identified in these two clinical entities. A predominant Th17-driven immune response may play an important role in the immunopathogenesis of idiopathic AAU, while Th1 dominant immune response may be responsible for the inflammation in HLA-B27 associated AAU.

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.

The Rate of Helicobacter pylori Seropositivity in a Group of Korean Patients with HLA-B27-Associated Acute Anterior Uveitis.

PURPOSE: To investigate an association between Helicobacter pylori seropositivity and HLA-B27-positive acute anterior uveitis (AAU) in Korean patients. METHODS: Retrospective analysis was performed with data from 106 patients previously diagnosed with AAU without clinical evidence of spondyloarthropathy. Serum immunoglobulin G antibodies to H. pylori were measured by enzyme-linked immunosorbent assay, and HLA typing was performed using polymerase chain reaction of DNA amplification. We included 72 non-uveitis patients and 35 age- and sex-matched healthy controls in the study. RESULTS: Of the 106 patients with AAU, 41 (38.7%) were HLA-B27-positive, and 45 (42.5%) were seropositive for H. pylori. Patients with HLA-B27-positive AAU had a significantly lower prevalence of H. pylori seropositivity compared to those with HLA-B27-negative AAU and healthy controls (24.4% vs. 53.8%, p = 0.003; 24.4% vs. 57.1%, p = 0.004, respectively). In the non-uveitis group, however, HLA-B27-positive patients exhibited similar H. pylori seropositivity prevalence to HLA-B27-negative patients and healthy controls (45.5% vs. 55.7%, p = 0.529; 45.5% vs. 57.1%, p = 0.497, respectively). In multivariate analysis, a low prevalence of H. pylori seropositivity was significantly associated with HLA-B27-positive AAU (odds ratio = 0.340, 95% confidence interval 0.135-0.855, p = 0.022). CONCLUSIONS: Our results suggest an inverse association between H. pylori seropositivity and HLA-B27-positive AAU. Further investigation of this association is needed, given the low prevalence of H. pylori seropositivity observed in patients with HLA-B27-positive AAU.