肠道菌群与过敏性哮喘

近年来随着过敏性哮喘发病率的持续升高,人们开始注意到环境、生活方式的改变可能会影响过敏性哮喘的发生。流行病学调查显示,过敏性哮喘的发生和发展与生命早期肠道菌群的紊乱密切相关。本研究主要综述近年来肠道菌群对过敏性哮喘发生的影响及机制,探讨影响肠道菌群定植的主要因素,以及微生态调节剂在过敏性哮喘等变应性疾病中的预防和治疗作用。     

Extrinsic allergic alveolitis

Extrinsic allergic alveolitis is caused by the inhalation of small organic allergen particles by non-atopic subjects which provoke an allergic reaction, thought to be chiefly due to a type III mechanism, in the peripheral respiratory tissues. The clinical features are determined by the nature of exposure, the immunopathological mechanism(s) involved and the site of reaction in the lung. When the exposure is intermittent and intensive, febrile episodes with respiratory symptoms beginning after four to six hours are prominent, but when it is more continuous and less intensive they are not and the features are those of a chronic fibrosing lung disease. The diagnosis is important to make because management by the avoidance of exposure is followed by improvement. It is made by recognizing the clinical presentation, by identifying the source of allergen exposure and by obtaining supportive evidence from precipitin and skin tests, or from allergen inhalation tests or lung biopsy.     

浅部真菌感染和变态反应性皮肤病相关性研究

目的 通过比较合并与未合并浅部真菌感染的变态反应性皮肤病对常用变应原的敏感性,综合从皮肤或指(趾)甲中分离出的菌种情况,评估浅部真菌感染在变态反应性皮肤病的病因学中的作用.方法 受试者包括353例慢性荨麻疹、湿疹及特应性皮炎患者.通过真菌直接镜检法将受试者分为两组.实验组:变态反应性皮肤病合并浅部真菌感染组(n =173);对照组:变态反应性皮肤病无浅部真菌感染组(n=180).对所有实验组及对照组受试者进行9种真菌变应原和9种非真菌变应原皮内试验.实验组患者进一步进行真菌培养以鉴定菌种.结果 慢性荨麻疹患者实验组须发癣菌、新月弯孢霉,特异青霉、烟曲霉变应原阳性率显著高于对照组(P＜0.05),慢性湿疹患者实验组须发癣菌变应原阳性率显著高于对照组(P ＜0.001).慢性湿疹、荨麻疹患者其他真菌变应原及粉尘螨、屋尘螨等非真菌变应原阳性率比较差异均无统计学意义(P＞0.05).134例患者皮肤或指(趾)甲分离鉴定主要为红色毛癣菌(52.86％)、须癣毛癣菌(14.18％)、絮状表皮癣菌(5.22％)、白念珠菌(6.72％),实验组须发癣菌变应原阳性率及皮肤分离皮肤癣菌阳性率比较差异无统计学意义(P＞0.05).结论 实验结果表明,须发癣菌变应原阳性的慢性荨麻疹、湿疹患者往往合并皮肤癣菌感染,皮肤癣菌感染可能在部分慢性荨麻疹、湿疹的病因学中起重要作用.     

Toxocara canis and the allergic process

The protective effect of infectious agents against allergic reactions has been thoroughly investigated. Current studies have demonstrated the ability of some helminths to modulate the immune response of infected hosts. The objective of the present study was to investigate the relationship between Toxocara canis infection and the development of an allergic response in mice immunised with ovalbumin (OVA). We determined the total and differential blood and bronchoalveolar lavage fluid cells using BALB/c mice as a model. To this end, the levels of interleukin (IL)-4, IL-5 and IL-10 and anti-OVA-IgE were measured using an ELISA. The inflammatory process in the lungs was observed using histology slides stained with haematoxylin and eosin. The results showed an increase in the total number of leukocytes and eosinophils in the blood of infected and immunised animals at 18 days after infection. We observed a slight lymphocytic inflammatory infiltrate in the portal space in all infected mice. Anti-OVA-IgE levels were detected in smaller proportions in the plasma of immunised and infected mice compared with mice that were only infected. Therefore, we concluded that T. canis potentiates inflammation in the lungs in response to OVA, although anti-OVA-IgE levels suggest a potential reduction of the inflammatory process through this mechanism.     

Environmental factors and allergic airway diseases

A number of epidemiological studies show that in the last few decades, all over Europe, there has been a growing increase in allergic respiratory disease, which affects between 15 to 30% of the population. There is compelling evidence that this rise in allergic illnesses depends mainly on the type of the environmental pollution and on the typical lifestyle of western countries. Community-based studies comparing people living in former East and West Germany have proved a high prevalence of allergic respiratory disease in West German cities, with variances due to the differences in indoor and outdoor pollution. Ozone, nitrogen oxides, and respirable particulate matter (PM10) are the main components of photochemical smog, typical of western countries. They can lead to sensitization and the onset of allergic illnesses with direct and indirect mechanisms. The casual relationship between automobile traffic-generated pollution, in particular diesel exhaust particles which act as adjuvant on pollen sensitization, and the increase in allergic sensitization to pollens was proved by epidemiological observations, which were later confirmed by studies of animal laboratory exposure. Indoor environment is probably as important in increasing the prevalence of allergic disease. Different housing habits, energy-efficient buildings, and modern air-handling systems have reduced ventilation and produced substantial changes in indoor environment and an increased exposure to allergens (housedust mites, mould and pets dander in particular). Like outdoor pollution, tobacco smoke, formaldehyde, volatile organic compounds, fire burning products, and other chemicals can enhance allergic sensitization with direct and indirect mechanisms. Increased exposure to allergens in the early years of life can influence the immune regulation and the evolution towards a prevailing Th2 response. Recent epidemiological observations lead us to conclude that in the onset of allergic airway illnesses environmental factors can play a greater role than genetic predisposition. This revised version was published online in June 2006 with corrections to the Cover Date.     

Regulatory T cells and allergic asthma

Because of the characteristic airway inflammation observed in allergic asthma, the pathogenesis of this disease may be due, in part, to a lack of anti-inflammatory and immune suppressive mechanisms. Here, we discuss the possible involvement and therapeutic use of T regulatory cells and their soluble factors in this multifactorial disease.     

Air pollution and allergic airway diseases

In the last decades, many studies have shown an increase in the prevalence of allergic rhinitis and asthma mainly in urban communities, especially in industrialized countries. Airborne pollutants such as diesel exhaust particles, ozone, nitrogen dioxide and sulphur dioxide have been implicated in the initiation and exacerbation of allergic airway diseases. Epidemiologic studies have shown clear associations between air pollution and allergic diseases, in vivo and in vitro studies have provided biologic link and potential molecular mechanisms. Particulate and gaseous pollutants can act both on the upper and lower airways to initiate and exacerbate cellular inflammation through interaction with the innate immune system. As a consequence, increased non-specific airway hyper-responsiveness and airway resistance have been observed in man. Diesel exhaust particles can both induce and exacerbate in vivo allergic responses. They can also modify the immune system's handling of the allergen. The effects of gaseous pollutants on immune responses to allergens are not fully understood. We review the different mechanisms involved in the enhancement of allergic inflammation by urban air pollutants, including effects on cytokine and chemokine production, as well as activation of different immune cells. We discuss the hypothesis that pollutants' effects on the immune system involve hierarchical oxidative stress. Susceptibility genes to air pollution inducing allergic diseases are also discussed.     

Dissociation of experimental allergic encephalomyelitis protective effect and allergic side reactions in tolerization with neuroantigen

Administration of autoantigens under conditions that induce type 2 immunity frequently leads to protection from T cell-mediated autoimmune diseases. Such treatments, however, are inherently linked to the induction of IgG1 Abs and to the risk of triggering anaphylactic reactions. We studied the therapeutic benefit vs risk of immune deviation in experimental allergic encephalomyelitis of SJL mice induced by MP4, a myelin basic protein-proteolipid protein (PLP) fusion protein. MP4 administration in IFA induced type 2 T cell immunity, IgG1 Abs, and experimental allergic encephalomyelitis protection, and all three were enhanced by repeat injections. Despite high Ab titers, anaphylactic side reactions were not observed when MP4 was repeatedly injected in IFA or as soluble Ag s.c. In contrast, lethal anaphylaxis was seen after s.c. injection of soluble PLP:139-151 peptide, but not when the peptide was reinjected in IFA. Therefore, the Ab response accompanying the immune therapy constituted an anaphylactic risk factor only when the autoantigen was not retained in an adjuvant and when it was small enough to be readily disseminated within the body. Taken together, our data show that treatment regimens can be designed to boost the protective type 2 T cell response while avoiding the risk of Ab-mediated allergic side effects.     

IgG transmitted from allergic mothers decreases allergic sensitization in breastfed offspring

Background

A. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which are responsible for stimulation of immune responses. Study of the dynamics of allergen production by fungi may lead to insights into how allergens are presented to the immune system.

Methods

Expression of 17 A. fumigatus allergen genes was examined in response to various culture conditions and stimuli as well as in the presence of macrophages in order to mimic conditions encountered in the lung.

Results

Expression of 14/17 allergen genes was strongly induced by oxidative stress caused by hydrogen peroxide (Asp f 1, -2, -4, -5, -6, -7, -8, -10, -13, -17 and -18, all >10-fold and Asp f 11, -12, and -22, 5-10-fold) and 16/17 allergen genes were repressed in the presence of cAMP. The 4 protease allergen genes (Asp f -5, -10, -13 and -18) were expressed at very low levels compared to the comparator (β-tubulin) under all other conditions examined. Mild heat shock, anoxia, lipid and presence of macrophages did not result in coordinated changes in allergen gene expression. Growth on lipid as sole carbon source contributed to the moderate induction of most of the allergen genes. Heat shock (37°C > 42°C) caused moderate repression in 11/17 genes (Asp f 1, -2, -4, -5, -6, -9, -10, -13, -17, -18 and -23) (2- to 9-fold), which was mostly evident for Asp f 1 and -9 (~9-fold). Anaerobic stress led to moderate induction of 13/17 genes (1.1 to 4-fold) with one, Asp f 8 induced over 10-fold when grown under mineral oil. Complex changes were seen in gene expression during co-culture of A. fumigatus with macrophages.

Conclusions

Remarkable coordination of allergen gene expression in response to a specific condition (oxidative stress or the presence of cAMP) has been observed, implying that a single biological stimulus may play a role in allergen gene regulation. Interdiction of a putative allergen expression induction signalling pathway might provide a novel therapy for treatment of fungal allergy.