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.

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.

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.

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.

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.

Plasma metabonomics study of the patients with acute anterior uveitis based on ultra-performance liquid chromatography-mass spectrometry.

BACKGROUND: The identification of the biomarkers of patients with acute anterior uveitis (AAU) may allow for a less invasive and more accurate diagnosis, as well as serving as a predictor in AAU progression and treatment response. The aim of this study was to identify the potential biomarkers and the metabolic pathways from plasma in patients with AAU. METHODS: Both plasma metabolic biomarkers and metabolic pathways in the AAU patients versus healthy volunteers were investigated using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and a metabonomics approach. The principal component analysis (PCA) was used to separate AAU patients from healthy volunteers as well as to identify the different biomarkers between the two groups. Metabolic compounds were matched to the KEGG, METLIN, and HMDB databases, and metabolic pathways associated with AAU were identified. RESULTS: The PCA for UPLC-MS data shows that the metabolites in AAU patients were significantly different from those of healthy volunteers. Of the 4,396 total features detected by UPLC-MS, 102 features were significantly different between AAU patients and healthy volunteers according to the variable importance plot (VIP) values (greater than two) of partial least squares discriminate analysis (PLS-DA). Thirty-three metabolic compounds were identified and were considered as potential biomarkers. Meanwhile, ten metabolic pathways were found that were related to the AAU according to the identified biomarkers. CONCLUSIONS: These data suggest that metabolomics study can identify potential metabolites that differ between AAU patients and healthy volunteers. Based on the PCA, PLS-DA, several potential metabolic biomarkers and pathways in AAU patients were found and identified. In addition, the UPLC-MS technique combined with metabonomics could be a suitable systematic biology tool in research in clinical problems in ophthalmology, and can provide further insight into the pathophysiology of AAU.

The expression and significance of T helper cell subsets and regulatory T cells CD4⁺ CD25⁺ in peripheral blood of patients with human leukocyte antigen B27-positive acute anterior uveitis.

BACKGROUND: Human leukocyte antigen B27 (HLA-B27)-associated uveitis is the most common reason for non-infectious uveitis. This purpose of the research was to study the expression and significance of T lymphocyte subsets and CD4⁺ CD25⁺ T regulatory (Treg) cells in peripheral blood of patients with Human leukocyte antigen B27-positive acute anterior uveitis (HLA-B27-positive AAU). METHODS: The concentrations of Th1, Th2, Th17, CD4⁺ CD25⁺and CD4⁺ CD25⁺FOXP3⁺ Treg cells in peripheral blood were tested by flow cytometry. C-reactive protein (CRP) in peripheral blood was detected by immunoturbidimetry (ITM). Spearman's rank correlation was used to analyze the relationships between the concentration of Th1, Th2, Th17, CD4⁺ CD25⁺, and CD4⁺ CD25⁺ FOXP3(+) Treg cells in peripheral blood and disease activity score and CRP content. RESULTS: The ratio of both γ [interferon (IFN)-γ] (+)CD4⁺Th1 cells and CD4⁺IL-17⁺Th17 cells in peripheral blood of patients with HLA-B27-positive AAU (P = 0.041) was higher than that of the control group (P = 0.002). The concentration of CD4⁺ CD25⁺ FOXP3(+) T cells in peripheral blood of patients with AAU was lower than that of the control group (P = 0.026). The concentration of Th1 cells in peripheral blood of the patients had no correlation with disease activity score (P = 0.50) or CRP content (P = 0.383). This was also true of the concentration of Th2 cells (Disease activity score: R = 0.068, P = 0.817; CRP content: R = 0.439, P = 0.116). Th17 cell concentration positively correlated with disease activity score (R = 0.805, P = 0.001). The concentration of CD4⁺ CD25⁺ T cells showed no correlation with disease activity score (R =-0.209, P = 0.472) or CRP content (R =-0.169, P = 0.563), whereas the concentration of CD4⁺ CD25⁺ FOXP3⁺ T cells negatively correlated with disease activity score but did not correlate with CRP (R =-0.248, P = 0.392). CONCLUSIONS: The peripheral blood of patients with HLA-B27-positive AAU showed a higher expression of interferon-γ and interleukin-17 cells in CD4⁺T cells, whereas CD4⁺CD25⁺FOXP3⁺ T cells displayed a lower expression of the cytokines. The balance between Th17 cells and CD4⁺ CD25⁺ FOXP3⁺ T cells may contribute to the activity of HLA-B27-positive AAU.

[Screening of key genes and inflammatory signalling pathway involved in the pathogenesis of HLA-B27-associated acute anterior uveitis by gene expression microarray].

OBJECTIVE: To investigate the genes and signalling pathways located upstream of the inflammatory processes in human leukocyte antigen (HLA)-B27-associated acute anterior uveitis by gene expression microarray. METHODS: Experimental study. HLA-B27-positive and-negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS). Gene expression microarrays were used to identify the differentially expressed genes. Differentially expressed (DE) genes were testified by real-time PCR and analyzed by a series of bioinformatics-based techniques such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes. RESULTS: Gene expression microarray analysis revealed marked differences between HLA-B27-positive acute anterior uveitis (AAU) and HLA-B27-negative healthy control peripheral monocytes in the genes that were upregulated in response to LPS stimulation with 1105 genes and 25 genes respectively. Gene Ontology enrichment and pathway analysis indicated that genes participating in protein transport and folding were essential to the inflammatory process. The LPS receptor-Toll-like receptor (TLR)4 induced TLR signalling pathway and pathway related to Vibrio cholerae infection were located upstream of the network and contribute to the overall response. Among the DE genes, PIK3CA, PIK3CB, AKT3, and MAPK1 might play critical roles in inflammation. CONCLUSIONS: Equivalent LPS stimulation induces a different response in HLA-B27-positive peripheral monocytes compared to normal control, suggesting that the TLR pathway is involved in the pathogenesis of HLA-B27-associated AAU.

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.

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.

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.

Serum haptoglobin levels in ocular Behçet disease and acute phase proteins in the course of Behçet disease.

PURPOSE: Changes in concentrations of acute phase proteins in the serum of patients might be significant in the pathogenesis of Behçet disease. This report investigates the association between ocular disease activity and serum haptoglobin levels in patients with Behçet disease, and summarizes the current understanding of the correlation between acute phase proteins and Behçet disease based on both personal studies and data from the literature. METHODS: Thirty patients with Behçet disease with ocular involvement and 15 healthy subjects were included in the study. Of the 30 patients, 14 had acute uveitis and 16 had inactive ocular involvement at the time of enrollment. RESULTS: There was a significant difference in haptoglobin levels between the patients with active ocular disease and controls (p=0.0005). There was also a significant difference in haptoglobin levels between the patients with inactive ocular disease and control subjects (p<0.0001). However, no significant difference was observed among patients with active versus inactive uveitis with regard to serum haptoglobin levels. CONCLUSIONS: Higher serum haptoglobin levels in patients with Behçet disease compared to control subjects were obtained. However, elevated serum haptoglobin levels do not seem to be a risk factor for uveitis activity. Behçet disease is generally diagnosed by physical examinations and no laboratory marker has been widely accepted for follow-up of disease activity.

Serum prolactin levels in HLA-B27-associated uveitis.

PURPOSE: To evaluate basal serum prolactin levels in patients with HLA-B27-associated uveitis. METHODS: Prospective, nonrandomized comparative trial. Thirty-three patients with HLAB27- associated uveitis and 30 age- and sex-matched healthy control subjects were included. Age, systemic disease, treatment, and uveitis activity were recorded for comparative analysis between groups. Fourteen out of 23 patients with arthritic disease had ankylosing spondylitis. Basal serum prolactin levels were determined by electrochemiluminescence immunoassay on a Modular Analytics E170 analyzer. RESULTS: Prolactinemia was significantly higher (mean=15.84 ng/mL) in patients vs controls (mean=11.50 ng/mL) (p=0.026). Subgroup analysis revealed prolactinemia in arthritic disease patients (mean=17.21 ng/mL) significantly higher than controls (mean=11.50 ng/mL) (p=0.009) and in ankylosing spondylitis (mean=17.65 ng/mL) vs controls (mean=11.50 ng/mL) (p=0.006). No correlation was found between prolactinemia and systemic treatment. Prolactinemia did not correlate with disease activity. Autoimmunity features also correlated with higher prolactinemia (mean=17.26 ng/mL) vs controls (mean=11.50 ng/mL) (p=0.015). CONCLUSIONS: These results suggest the role of serum prolactin levels in HLA-B27-associated uveitis pathogenesis and its subgroups. There was no correlation with disease activity.

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.

Changes in Toll-like receptor (TLR)-2 and TLR4 expression and function but not polymorphisms are associated with acute anterior uveitis.

PURPOSE: To investigate the expression and polymorphisms of Toll-like receptor (TLR)-2 and -4 in the peripheral neutrophils and monocytes of patients with acute anterior uveitis (AAU). METHODS: Nine patients with active AAU and nine age- and sex-matched healthy control subjects were studied. TLR2 and -4 protein expression on CD16(+) neutrophils and CD14(+) monocytes were studied by flow cytometry. TLR function was investigated by whole-blood stimulation with lipopolysaccharide and peptidoglycan for TLR4 and -2 activation, respectively. Proinflammatory cytokine production in response to TLR stimulation was determined by multiplex cytokine bead arrays of the culture supernatant. TLR2 and -4 genotypes were determined by RFLP-PCR. RESULTS: A significant reduction in the levels of TLR2 expression was observed on the neutrophils and monocytes of patients with active AAU compared with that of healthy control subjects (P < 0.05). IL-6 and IFN-gamma production stimulated by TLR4 activation was significantly reduced in patients with AAU, compared with that in healthy control subjects (P < 0.05). In contrast, significantly increased production of IL-1beta in response to TLR2 stimulation was observed in patients with AAU (P < 0.05). There was no correlation between the TLR2 or -4 genotypes and the observed differential functional responses to TLR stimulation. CONCLUSIONS: There is a selective perturbation in the expression and function of TLR2 and -4, which could be consistent with a state of endotoxin tolerance, in patients with active AAU. The results support a role for microbial triggers and TLRs in the pathogenesis of AAU.

Serum cytokine levels in active uveitis and remission.

Serum levels of interleukin(IL)-8, IL-6, and (TNF)-alpha were measured in 25 patients during active uveitis and uveitis in remission and compared to age-matched controls. Levels of IL-8 and IL-6 were significantly elevated in patients with active disease and were decreased during remission. IL-8 levels were highest in patients with anterior uveitis, with greatest difference between active disease and remission. No consistent pattern was observed for TNF-alpha. In conclusion, serum cytokine levels are elevated in active noninfectious uveitis. The rise in IL-8 may suggest innate immune mechanisms in the acute disease, while IL-6 participates in modulation of inflammation in the chronic 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.

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.

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.