Ocular manifestations of Behçet's disease in children and adults: a systematic review and meta-analysis.

OBJECTIVES: Children and adults may develop Behçet's disease (BD), often with ocular involvement such as uveitis. This study aimed to determine the prevalence and type of ocular manifestations in childhood and adult BD. METHODS: Medline, Web of Science and Cochrane databases were searched from inception to October 5, 2018 to identify publications related to Behçet's disease comprising minimum twenty patients and providing the frequency of ocular manifestations (OC). Random effects models were used to combine the prevalence of OC in adults and children with BD. Heterogeneity was evaluated using I2. RESULTS: The search resulted in 3129 articles, of which 51 were included in meta-analysis. OCs were slightly more frequent in childhood onset BD with the mean [95% Confidence Interval] frequency of 45 [34-56%] compared to 36 [29-43%] in adults, however, this difference was not statistically significant (p=0.198). In both children and adults, posterior uveitis (children 27% vs. adults 25%, and retinal vasculitis in adults 16%) was the most common ocular manifestation, followed by anterior uveitis (children 18% vs. adults 23%). When comparing the distribution of OC in Behcet's in adults, there was geographic variation where OC were higher in Turkey and the Middle East 42%, followed by Europe and North America (36%), North Africa 26% and East Asia 25% but not significantly (p=0.27). CONCLUSIONS: Ocular manifestations, predominantly uveitis; are common in BD. Ocular manifestations are not proportionately more frequent in adults with BD along the ancient Silk Road.

Ocular Manifestations in Rheumatoid Arthritis, Connective Tissue Disease, and Vasculitis: A Systematic Review and Metaanalysis.

OBJECTIVE: Rheumatoid arthritis (RA) and other rheumatic diseases may present with ocular manifestations.The purpose of our work was to determine the prevalence and type of eye involvement in RA and other connective tissue diseases through a metaanalysis and literature review. METHODS: A systematic review of the literature was performed using Medline, Web of Science, and the Cochrane Library from their inceptions until January 7, 2019. Conjunctivitis, keratoconjunctivitis sicca, xeropthalmia, uveitis, eye hemorrhage, optic neuritis, papilledema, orbital disease, retinal artery/vein occlusion, macular edema, retinitis, chorioretinitis, scleritis, iridocyclitits, choroid hemorrhage, blindness, and amaurosis fugax were searched for prevalence in patients with RA, systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), dermatomyositis, polymyositis, systemic sclerosis, Sjögren syndrome (SS), undifferentiated connective tissue disease, giant cell arteritis, granulomatosis polyangiitis (GPA; formerly Wegener granulomatosis), systemic vasculitis, and sarcoidosis. RESULTS: There were 3394 studies identified and 65 included. The prevalence of eye involvement was 18% in RA, 26% in GPA, 27% in giant cell arteritis, 27% in sarcoidosis, 31% in SLE, and 35% in APS. The most common manifestation was dry eye syndrome ("dry eye"; keratoconjunctivitis sicca) in most diseases analyzed, with an especially high frequency of 89% in SS. Anterior and posterior uveitis were the most common ocular complications in sarcoidosis, occurring in 16% (95% CI 3-28) and 6% (95% CI 3-9) of patients, respectively. CONCLUSION: Eye involvement is present in approximately one-fifth of patients with RA, and a one-quarter to one-third of patients with connective tissue diseases (other than SS at 89%) and vasculitis.

The frequency of uveitis in patients with adult versus childhood spondyloarthritis.

OBJECTIVES: This meta-analysis investigated the frequency of ocular involvement in childhood and adult spondyloarthritis (SpA). METHODS: A systematic review of the literature was conducted. Medline, Web of Science and Cochrane databases were searched upto October 2018 identifying publications related to SpA, including ankylosing spondylitis (AS) with ocular conditions (OC) (uveitis, iritis, retinitis, chorioretinitis and other ocular involvement). The rates of OC were extracted and random effects models estimated their frequency. Heterogeneity was evaluated using I2. Inclusion criteria were studies in SpA of either children or adults who included a frequency of OC. RESULTS: 3164 studies were identified, and 41 analysed which included frequencies of uveitis/iritis. Other OC were too infrequent to analyse. A pooled random effects model showed that the prevalence of uveitis was 24% in adult AS (23 studies, 11 943 patients), 10% in adult psoriatic arthritis (PsA) (9 studies, 1817) and 17% in undifferentiated adult SpA (9 studies, 6568 patients). In juveniles with AS, the prevalence of uveitis was 27% (8 studies, 927 patients), in juvenile PsA it was 16% (5 studies, N=498) and in juvenile undifferentiated SpA, uveitis occurred in 7% (2 studies, 1531 patients). In all evaluated SpA subgroups, there were no statistical differences in the frequency of uveitis between juveniles and adults. CONCLUSIONS: Uveitis in adult versus child-onset SpA is similar in AS but more common in adult-onset undifferentiated SpA, and less frequent in adult-onset PsA compared to child-onset PsA, but the differences were not significant.

The frequency of uveitis in patients with juvenile inflammatory rheumatic diseases.

OBJECTIVES: This meta-analysis investigated the frequency and type of ocular involvement in juvenile inflammatory arthritis (JIA) and other juvenile rheumatic diseases. METHODS: Medline, Web of Science and Cochrane databases were searched from inception to September 2018 to identify publications related to juvenile arthritis and rheumatic diseases, which reported frequency of Uveitis in juvenile rheumatic conditions and contained at least 20 patients. The prevalence and type of eye complications were extracted, and random effects models estimated their frequency. Heterogeneity was evaluated using I2. RESULTS: In total, 7132 unique citations resulted in 59 articles included. Pooled frequency of uveitis was: 24% in oligoarticular JIA, 12% in polyarticular JIA, 1% in systemic JIA, 50% in pediatric Bechet's, 9% in juvenile psoriatic arthritis, 24% in juvenile spondyloarthropathy and 5% in juvenile systemic lupus erythematosus. The most common uveitis in JIA was anterior uveitis, which occurred in 14%; also described as iridocyclitis in 10% of patients. Publication bias was negligible for all conditions except those with few reported studies (juvenile SLE and systemic JIA). Uveitis in JIA was more common in Europe (14%), North America (11%) and the Middle East (12%) than East Asia (7%) and Oceania (3%). CONCLUSIONS: Ocular involvement (mostly uveitis) in juvenile inflammatory arthritis and other pediatric rheumatic diseases varied between 3% and 50% depending on the underlying condition; and was highest in pediatric Bechet's. In JIA, the highest frequency of uveitis was in oligoarticular JIA; with anterior uveitis being the most frequent type of uveitis. There was variation geographically for uveitis in JIA.

CD1d-independent activation of mouse and human iNKT cells by bacterial superantigens.

Invariant NKT (iNKT) cells are infrequent but important immunomodulatory lymphocytes that exhibit CD1d-restricted reactivity with glycolipid Ags. iNKT cells express a unique T-cell receptor (TCR) composed of an invariant α-chain, paired with a limited range of ß-chains. Superantigens (SAgs) are microbial toxins defined by their ability to activate conventional T cells in a TCR ß-chain variable domain (Vß)-specific manner. However, whether iNKT cells are directly activated by bacterial SAgs remains an open question. Herein, we explored the responsiveness of mouse and human iNKT cells to a panel of staphylococcal and streptococcal SAgs and examined the contribution of major histocompatibility complex (MHC) class II and CD1d to these responses. Bacterial SAgs that target mouse Vß8, such as staphylococcal enterotoxin B (SEB), were able to activate mouse hybridoma and primary hepatic iNKT cells in the presence of mouse APCs expressing human leukocyte antigen (HLA)-DR4. iNKT cell-mediated cytokine secretion in SEB-challenged HLA-DR4-transgenic mice was CD1d-independent and accompanied by a high interferon-γ:interleukin-4 ratio consistent with an in vivo Th1 bias. Furthermore, iNKT cells from SEB-injected HLA-DR4-transgenic mice, and iNKT cells from SEB-treated human PBMCs, showed early activation by intracellular cytokine staining and CD69 expression. Unlike iNKT cell stimulation by α-galactosylceramide, stimulation by SEB did not induce TCR downregulation of either mouse or human iNKT cells. We conclude that Vß8-targeting bacterial SAgs can activate iNKT cells by utilizing a novel pathway that requires MHC class II interactions, but not CD1d. Therefore, iNKT cells fulfill important effector functions in response to bacterial SAgs and may provide attractive targets in the management of SAg-induced illnesses.

Protein glycosylation in Helicobacter pylori: beyond the flagellins?

Glycosylation of flagellins by pseudaminic acid is required for virulence in Helicobacter pylori. We demonstrate that, in H. pylori, glycosylation extends to proteins other than flagellins and to sugars other than pseudaminic acid. Several candidate glycoproteins distinct from the flagellins were detected via ProQ-emerald staining and DIG- or biotin- hydrazide labeling of the soluble and outer membrane fractions of wild-type H. pylori, suggesting that protein glycosylation is not limited to the flagellins. DIG-hydrazide labeling of proteins from pseudaminic acid biosynthesis pathway mutants showed that the glycosylation of some glycoproteins is not dependent on the pseudaminic acid glycosylation pathway, indicating the existence of a novel glycosylation pathway. Fractions enriched in glycoprotein candidates by ion exchange chromatography were used to extract the sugars by acid hydrolysis. High performance anion exchange chromatography with pulsed amperometric detection revealed characteristic monosaccharide peaks in these extracts. The monosaccharides were then identified by LC-ESI-MS/MS. The spectra are consistent with sugars such as 5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Ac7Ac) previously described on flagellins, 5-acetamidino-7-acetamido-3,5,7,9-tetradeoxy-L-glycero-L-manno-nonulosonic acid (Pse5Am7Ac), bacillosamine derivatives and a potential legionaminic acid derivative (Leg5AmNMe7Ac) which were not previously identified in H. pylori. These data open the way to the study of the mechanism and role of protein glycosylation on protein function and virulence in H. pylori.