HLA antigens in uveitis

HLA antigens are associated with a number of inflammatory eye diseases, most notably HLA B2 with anterior uveitis (AU). This association varies between different populations and ethnic groups. The aim of this study was to investigate the relationship between uveitis and HLA A, B and DR locus antigens in an Australian population. Seventy-two consecutive patients with uveitis were studied (37 males and 35 females) over a 6 month period. Thirty-two percent of the AU patients were HLA B27+, as were 42% of males (19% females) with their first attack of AU compared with 60% of males (23% females) with recurrent AU. The only significant difference in etiology between males and females was the greatly increased incidence of rheumatic diseases in males, in whom 77% (10/13) had radiological evidence of sacroiliitis. Additional findings included a lack of association between the HLA B7 cross reactive group and DR locus antigens in AU as well as the lack of any HLA associations in the 13 patients with posterior uveitis (PU).     

从宏观结构及微观分布揭示医学学科发展战略情报

选择ESI免疫学高被引论文为数据源,对高频主题词与来源文献进行双聚类分析,绘制战略坐标图谱和社会网络图谱并将两者结果相互融合嵌入。社会网络分析嵌入战略坐标,从宏观结构和微观分布揭示全球免疫学领域热点结构与内部主题分布情况,为该领域发展方向提供参考。     

Orofacial anatomical and occlusal changes in patients with sickle cell disease in Kuwait

ObjectiveSickle cell disease (SCD) is the most common hemoglobinopathy where morphologic changes to red blood cells affect the development of hard and soft tissues. The purpose of this study is to identify the craniofacial characteristics and maxillomandibular relationship in SCD patients and compare with unaffected subjects, through cephalometric radiographic assessment.Materials and MethodsThe study included 44 Kuwaiti SCD patients (20 female, 24 male) as well as 44 age and gender matched controls. Digital lateral cephalometric, radiographs were recorded. SNA and ANB angles were measured and compared.ResultsThe mean SNA angle was found to be higher among the SCD cases (83.00 ± 3.22) than in controls (81.78 ± 4.58), but the difference was not statistically significant, (p = 0.146). The mean ANB angle in SCD cases (5.27 ± 2.36) was significantly higher, than that in controls (3.97 ± 2.23). The difference in means was statistically significant, (p = 0.01). Almost 50% of the SCD patients had class II malocclusion and 61.5% of the patients had prognathic maxilla.ConclusionsPatients with SCD in Kuwait exhibited characteristics of skeletal class II pattern malocclusion. They also showed evidence of compensatory maxillary expansion.     

In situ characterization of O-linked glycans of Muc2 in mouse colon

The characterization of mucus O-linked glycans in the proximal and distal mouse colon was performed by conventional histochemical methods and by lectin histochemistry in combination with enzymatic treatment (PNGase, α1,2 fucosidase, sialidase digestion), with and without prior desulfation. We demonstrated the presence of sialo- and sulfomucins in both the proximal and distal colon of the mouse. In the distal colon the sulfomucins were clearly prevalent, although there were always sialomucins with sialyl residues linked α2,6 to the subterminal galactose. Sialic acid was poorly O-acetylated, especially in the distal colon. The lectin binding pattern indicates a massive presence of fucose α1,2 linked to galactose in O-glycans and smaller quantities of fucose linked α1,6 to N-acetylglucosamine in the core of N-linked glycans. Lectin histochemistry also demonstrated the presence of glycosidic residues of N-acetylglucosamine, N-acetylgalactosamine, and galactose in oligosaccharide chains of highly sulfated mucins.     

siRNA-based spherical nucleic acids reverse impaired wound healing in diabetic mice by ganglioside GM3 synthase knockdown

Spherical nucleic acid (SNA) gold nanoparticle conjugates (13-nm-diameter gold cores functionalized with densely packed and highly oriented nucleic acids) dispersed in Aquaphor have been shown to penetrate the epidermal barrier of both intact mouse and human skin, enter keratinocytes, and efficiently down-regulate gene targets. ganglioside-monosialic acid 3 synthase (GM3S) is a known target that is overexpressed in diabetic mice and responsible for causing insulin resistance and impeding wound healing. GM3S SNAs increase keratinocyte migration and proliferation as well as insulin and insulin-like growth factor-1 (IGF1) receptor activation under both normo- and hyperglycemic conditions. The topical application of GM3S SNAs (50 nM) to splinted 6-mm-diameter full-thickness wounds in diet-induced obese diabetic mice decreases local GM3S expression by >80% at the wound edge through an siRNA pathway and fully heals wounds clinically and histologically within 12 d, whereas control-treated wounds are only 50% closed. Granulation tissue area, vascularity, and IGF1 and EGF receptor phosphorylation are increased in GM3S SNA-treated wounds. These data capitalize on the unique ability of SNAs to naturally penetrate the skin and enter keratinocytes without the need for transfection agents. Moreover, the data further validate GM3 as a mediator of the delayed wound healing in type 2 diabetes and support regional GM3 depletion as a promising therapeutic direction.Of 27 million Americans diagnosed with type 2 diabetes (T2D), more than 6 million have chronic, nonhealing skin wounds, particularly on the plantar surface, leading to secondary bacterial infection and costing the healthcare system more than $25 billion (1, 2). In 2010 alone, more than 70,000 individuals in the United States with T2D underwent amputation (3). Improved understanding of diabetic wound pathology and new interventions for impaired wound healing are needed.Ganglioside-monosialic acid 3 (GM3), the predominant sialylated glycosphingolipid in skin, has recently been recognized to be a critical mediator of insulin resistance (4–12). Indeed, we have recently shown three- and fourfold more GM3 synthase (GM3S; also known as SAT-I or ST3Gal-V), which is required for the synthesis of GM3, in diabetic human plantar skin than in site- and age-matched control skin (4). Similarly, skin samples from the backs of diet-induced obese (DIO) and ob/ob mouse diabetic models show increased GM3S mRNA expression and GM3 levels. Knockout (KO) of GM3S improves the insulin resistance induced by a high-fat diet in mouse adipose tissue, muscle (5), and as recently shown, skin of DIO T2D mice, reversing the wound-healing impairment of T2D (4). The acceleration of wound healing by GM3S KO and GM3 depletion in mouse skin is associated with increased epidermal cell migration and proliferation as well as activation of the epidermal insulin-like growth factor-1 receptor (IGF1R) in vivo (4). Isolated cultured mouse GM3S^−/− keratinocytes (KCs) migrate and proliferate more rapidly than GM3S^+/+ WT littermate KCs, resist the inhibition of migration and proliferation induced by increased ambient glucose (simulating hyperglycemia), and show activation of IGF1R and insulin receptor. These findings show that accelerated wound healing, at least in part, is reflected by a direct action of GM3S suppression on wound area KCs and suggest that a topical intervention to knock down GM3S in skin might accelerate the impaired wound healing in T2D.Spherical nucleic acids (SNAs; structures made by chemically modifying gold nanoparticles with dense layers of highly oriented oligonucleotides) are an emerging class of gene regulation entities that show promise for both antisense and RNAi pathways (13, 14). These structures can be rapidly synthesized from readily available nucleic acid and nanoparticle precursors and exhibit attractive biological properties, including nuclease resistance (15), the ability to rapidly enter cells through scavenger receptor-mediated endocytosis (16), and the ability to effect gene knockdown in several in vivo models without apparent cellular toxicity or off-target effects (17, 18). Previous studies have shown that SNAs, dispersed in a common moisturizer, can traverse the epidermal barrier in C57BL/6 mouse models and human skin equivalents and can be used to specifically down-regulate EGF receptor (EGFR) (17). Taken together, these properties point toward the potential for developing new topically applied gene regulation therapies for skin diseases. Herein, we report the development of siRNA-based GM3S SNA, which efficiently and specifically knocks down the expression of GM3S mRNA and protein in cultured KCs as well as both intact and wounded mouse skin. GM3S SNA treatment promotes KC migration into the wound bed, increases IGF1R and EGFR phosphorylation, and accelerates wound closure in T2D mice. This work constitutes an innovative approach to diabetic wound healing and represents the first topical therapeutic application, to our knowledge, of SNA nanotechnology. Moreover, it lays the groundwork for developing SNA approaches to treatment of many of the more than 200 skin-related disorders with a known genetic basis (19).     

Immunogenicity and safety of one dose of diphtheria,tetanus, acellular pertussis and poliomyelitis vaccine (Repevax) followed by two doses of diphtheria,tetanus and poliomyelitis vaccine (Revaxis) in adults aged ≥40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years

Introduction

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years.

Methods

This open-label, multicentre study was conducted in adults aged ≥40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥0.1 IU/mL by seroneutralization assay [SNA]); tetanus (≥0.1 IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥5 EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥0.01 IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose.

Results

Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5–96.8); tetanus and poliomyelitis, 100% (CI: 98.8–100). Percentage of participants with an antibody titre ≥5 EU/mL against pertussis antigens was ≥95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8–100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%).

Conclusions

This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an adult population to achieve maximal protection against diphtheria, tetanus, poliomyelitis and pertussis simultaneously.