北京协和医院346例慢性胰腺炎人口学特征、病因变迁及临床特点

目的：总结慢性胰腺炎（Chronic pancreatitis，CP）的临床特点及病因等的变化。 目的　探讨慢性胰腺炎（chronic pancreatitis，CP）的人口学特征、发病病因变迁和临床特点。方法　回顾性分析1983年1月至2008年12月北京协和医院346例CP住院患者的资料，总结其人口学特征、临床表现、病因和并发症情况。结果　346例CP患者中，男267例，女79例，男:女比例为3.38:1，发病年龄（44.34±15.88）岁。民族分布以汉族为最多（94.80%，328/346），职业分布以干部为最多（32.08%，111/346）。CP患者无论是患者总数还是入院人数占同期住院患者人数的比例均呈现快速增长的趋势。酒精(40.17%)和胆石症(41.04%)是最常见的CP病因因素。不同病因类型的CP均有明显的增长，以酒精性CP增长尤为显著，平均年增长率为108.7%。84.39 %（292/346）的患者有腹痛症状，56.07%（194/346）的患者有体重下降，24.86%（86/346）的患者有黄疸，均为梗阻性黄疸。CP并发症以糖尿病最为多见，占25.14%（87/346）。糖尿病和脂肪泻出现的病程中位时间分别在发病后1.00年和280.03个月，自身免疫性胰腺炎出现糖尿病早于特发性胰腺炎（P=0.020）。结论　我国CP发病人数在快速增长，酒精性CP的增长速度超过胆源性CP。腹痛与消瘦是CP最常见症状，糖尿病是CP最常见并发症。建立CP病例资料库并进行有序随诊将有助于总结CP流行病学规律和提高诊治经验。     

Expert Panel Workshop Consensus Statement on the Role of the Environment in the Development of Autoimmune Disease

Autoimmune diseases include 80 or more complex disorders characterized by self-reactive, pathologic immune responses in which genetic susceptibility is largely insufficient to determine disease onset. In September 2010, the National Institute of Environmental Health Sciences (NIEHS) organized an expert panel workshop to evaluate the role of environmental factors in autoimmune diseases, and the state of the science regarding relevant mechanisms, animal models, and human studies. The objective of the workshop was to analyze the existing data to identify conclusions that could be drawn regarding environmental exposures and autoimmunity and to identify critical knowledge gaps and areas of uncertainty for future study. This consensus document summarizes key findings from published workshop monographs on areas in which “confident” and “likely” assessments were made, with recommendations for further research. Transcribed notes and slides were reviewed to synthesize an overview on exposure assessment and questions addressed by interdisciplinary panels. Critical advances in the field of autoimmune disease research have been made in the past decade. Collaborative translational and interdisciplinary research is needed to elucidate the role of environmental factors in autoimmune diseases. A focus on exposure assessment methodology is needed to improve the effectiveness of human studies, and more experimental studies are needed to focus on causal mechanisms underlying observed associations of environmental factors with autoimmune disease in humans.     

Entropy of corneal nerve fibers distribution observed by laser scanning confocal microscopy: A noninvasive quantitative method to characterize the corneal innervation in Sjogren's syndrome patients

Sjogren's syndrome (SS) is a progressive autoimmune condition mainly affecting the salivary and lacrimal glands with an incidence of primary SS between 1/100 and 1/1,000. SS implies an alteration in the epithelium and subepithelium innervation, with consequent reduction of corneal sensitivity. It is necessary to have noninvasive quantitative methods to characterize the status of the corneal nerve fibers of the patients in order to choose and follow the best therapy. Entropy (information dimension) of the nerve corneal fibers distribution observed by confocal microscopy was evaluated in patients with primary SS (n = 30, 6 males, 24 females, 21–81 years), diagnosed by biopsy of salivary gland and blood tests and in sex‐ age‐matched healthy subjects (n = 12). Corneal nerve fiber density, Langerhans cell count, and cell density in the nerve plexus images were also evaluated. In selected patients salivary gland atrophy degree was also evaluated. Nerve corneal distribution observed by confocal microscopy is fractal. Entropy of the corneal nerve distribution statistically distinguishes between SS patients and healthy subjects: patients present a lower value of information dimension of the corneal nerve fibers distribution than healthy individuals (P < 0.001). Percentage of grouped cases classified by entropy according to the subjects (selected patients vs. healthy) showed a 100% sensitivity and 96% specificity, P < 0.0001 with a low value of coefficient of variation among the individuals (6–7 times lower than the other morphometric indexes). Entropy correlated with the severity of the disease (salivary gland atrophy degree, P < 0.01). Evaluation of entropy of the corneal nerve distribution observed by a laser confocal microscopy appears to quantitatively and noninvasively characterize an aspect of the SS patients in relation to the recognition of an impairment of their ocular surface, giving us for the first time a method to objectively and precisely characterize the corneal innervation status in the SS patients. Microsc. Res. Tech. 78:1069–1074, 2015. © 2015 Wiley Periodicals, Inc.     

The relationship between processing speed and working memory demand in systemic lupus erythematosus: Evidence from a visual n-back task.

Objective: Working memory (WM) deficits have been reported previously in systemic lupus erythematosus (SLE), but the relationship between information processing speed (PS) and WM deficits in SLE is unknown. This study examined whether or not PS slowing could account for the WM deficits observed in SLE. Method: A visual n-back task was used to measure simple and complex PS and WM in 40 SLE patients and 36 healthy controls. Simple PS was defined as reaction time (RT) to correct responses under a very low WM load condition (0-back), while complex PS was defined as RT to correct responses under moderate and high WM load conditions (1 and 2-back). Results: The results showed that SLE patients performed as well as the controls at the lower WM load conditions but had fewer correct responses than controls under the highest WM load condition (2-back). SLE patients had slower RTs than controls under all conditions, but they had relatively greater RT slowing than controls under the higher WM load conditions. Further, when RT for simple PS was subtracted from complex PS, SLE patients still showed slower complex PS for the 1- and 2-back compared with controls. Both simple and complex PS slowing were related to poorer accuracy scores on the 2-back condition, only for the SLE group. Conclusions: The n-back task provides a sensitive measure of PS and WM. The results suggest that PS deficits alone could not account for the WM deficits in SLE. Disease duration, disease activity, and depression did not appear to account for the observed PS and WM deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Gluten-Free Diet and Glycaemic Index in the Management of Coeliac Disease Associated with Type 1 Diabetes

ABSTRACT

Type 1 diabetes (T1D) is frequently associated with coeliac disease (CD). Individuals with concomitant diseases, should adhere to a strict gluten-free diet (GFD) and control glycaemia to avoid the complications associated with both conditions. However, many aspects of the GFD which is a highly eliminative diet is inferior, compared to conventional gluten-containing diet. In this review, the management of CD associated with T1D are presented and the treatment dilemmas concerning a GFD are discussed in the context of the glycaemic response of gluten-free products. A great deal was also focused on glycaemia control as potential protection against chronic diseases.     

Prenatal Vitamin D Deficiency Induces an Early and More Severe Experimental Autoimmune Encephalomyelitis in the Second Generation

In a previous study, we demonstrated that mouse adult F₁ offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F₂ females whose F₁ parents (males or females) were vitamin D-deprived when developing in the uterus of F₀ females. Unexpectedly, we observed that the vitamin D deficiency affecting the F₀ pregnant mice induced a precocious and more severe EAE in the F₂ generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents’ dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.     

Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes

The diagnosis of autoimmune polyglandular syndrome (APS) types 1/2 is difficult due to their rarity and nonspecific clinical manifestations. APS-1 development can be identified with assays for autoantibodies against cytokines, and APS-2 development with organ-specific antibodies. In this study, a microarray-based multiplex assay was proposed for simultaneous detection of both organ-specific (anti-21-OH, anti-GAD-65, anti-IA2, anti-ICA, anti-TG, and anti-TPO) and APS-1-specific (anti-IFN-ω, anti-IFN-α-2a, and anti-IL-22) autoantibodies. Herein, 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies or non-autoimmune endocrine pathologies and from healthy donors were analyzed. The prevalence of autoantibodies differed among the groups of healthy donors and patients with non-, mono- and multi-endocrine diseases. APS-1 patients were characterized by the presence of at least two specific autoantibodies (specificity 99.5%, sensitivity 100%). Furthermore, in 16 of the 18 patients, the APS-1 assay revealed triple positivity for autoantibodies against IFN-ω, IFN-α-2a and IL-22 (specificity 100%, sensitivity 88.9%). No anti-cytokine autoantibodies were found in the group of patients with non-APS-1 polyendocrine autoimmunity. The accuracy of the microarray-based assay compared to ELISA for organ-specific autoantibodies was 88.8–97.6%. This multiplex assay can be part of the strategy for diagnosing and predicting the development of APS.     

Granulomatous Inflammation in ANCA-Associated Vasculitis

ANCA-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). While systemic vasculitis is a hallmark of all AAV, GPA is characterized by extravascular granulomatous inflammation, preferentially affecting the respiratory tract. The mechanisms underlying the emergence of neutrophilic microabscesses; the appearance of multinucleated giant cells; and subsequent granuloma formation, finally leading to scarred or destroyed tissue in GPA, are still incompletely understood. This review summarizes findings describing the presence and function of molecules and cells contributing to granulomatous inflammation in the respiratory tract and to renal inflammation observed in GPA. In addition, factors affecting or promoting the development of granulomatous inflammation such as microbial infections, the nasal microbiome, and the release of damage-associated molecular patterns (DAMP) are discussed. Further, on the basis of numerous results, we argue that, in situ, various ways of exposure linked with a high number of infiltrating proteinase 3 (PR3)- and myeloperoxidase (MPO)-expressing leukocytes lower the threshold for the presentation of an altered PR3 and possibly also of MPO, provoking the local development of ANCA autoimmune responses, aided by the formation of ectopic lymphoid structures. Although extravascular granulomatous inflammation is unique to GPA, similar molecular and cellular patterns can be found in both the respiratory tract and kidney tissue of GPA and MPA patients; for example, the antimicrobial peptide LL37, CD163⁺ macrophages, or regulatory T cells. Therefore, we postulate that granulomatous inflammation in GPA or PR3-AAV is intertwined with autoimmune and destructive mechanisms also seen at other sites.     

Early-life food nutrition,microbiota maturation and immune development shape life-long health

ABSTRACT

The current knowledge about early-life nutrition and environmental factors that affect the interaction between the symbiotic microbiota and the host immune system has demonstrated novel regulatory target for treating allergic diseases, autoimmune disorders and metabolic syndrome. Various kinds of food nutrients (such as dietary fiber, starch, polyphenols and proteins) can provide energy resources for both intestinal microbiota and the host. The indigestible food components are fermented by the indigenous gut microbiota to produce diverse metabolites, including short-chain fatty acids, bile acids and trimethylamine-N-oxide, which can regulate the host metabolized physiology, immunity homeostasis and health state. Therefore it is commonly believed early-life perturbation of the microbial community structure and the dietary nutrition interference on the child mucosal immunity contribute to the whole life susceptibility to chronic diseases. In all, the combined interrelationship between food ingredients nutrition, intestinal microbiota configurations and host system immunity provides new therapeutic targets to treat various kinds of pathogenic inflammations and chronic diseases.