Mast cell activation syndrome: Proposed diagnostic criteria

The term mast cell activation syndrome (MCAS) is finding increasing use as a diagnosis for subjects who present with signs and symptoms involving the dermis, gastrointestinal track, and cardiovascular system frequently accompanied by neurologic complaints. Such patients often have undergone multiple extensive medical evaluations by different physicians in varied disciplines without a definitive medical diagnosis until the diagnosis of MCAS is applied. However, MCAS as a distinct clinical entity has not been generally accepted, nor do there exist definitive criteria for diagnosis. Based on current understanding of this disease "syndrome" and on what we do know about mast cell activation and resulting pathology, we will explore and propose criteria for its diagnosis. The proposed criteria will be discussed in the context of other disorders involving mast cells or with similar presentations and as a basis for further scientific study and validation.     

Mast cell activation syndrome—anesthetic challenges in two different clinical scenarios

Mast cell activation syndrome (MCAS) includes a group of disorders that result in the inappropriate release of inflammatory mediators from mast cells. These mediators can affect multiple organ systems and lead to significant morbidity, and possible fatality. Although reactions, typically in response to various nonspecific stimuli, are usually mild, they may put those with MCAS at increased risk of anaphylaxis. In this case report, we present two clinical scenarios of MCAS, and identify possible factors triggering mast cell mediator release. We also define a preoperative preventive pathway, outline anesthetic considerations, and discuss the management of immediate hypersensitivity reactions in patients with MCAS. Meticulous preoperative preparation, avoidance of triggers, and development of a plan to treat possible adverse organ responses are paramount of good outcomes.     

Sclerosing mediastinitis and mast cell activation syndrome

BACKGROUND: Sclerosing mediastinitis (ScM) is a rare, potentially life-threatening disorder, idiopathic in roughly half the cases. Systemic symptoms not attributable to sclerosis often appear in idiopathic ScM. Mast cell activation disease (MCAD) is a potential cause of these symptoms and also can cause sclerosis. ScM has not previously been associated with MCAD. Presented here are the first two cases of ScM associated with MCAD, specifically mast cell activation syndrome (MCAS). CASE 1: A 58-year-old chronically polymorbid woman developed ScM following matched sibling allogeneic stem cell transplantation. Eight years later MCAS, likely underlying most of her chronic issues, was identified. CASE 2: A 30-year-old chronically polymorbid woman presented with superior vena cava syndrome and was diagnosed with ScM. On further evaluation, MCAS was identified. Treatment promptly effected symptomatic improvement; sclerosis has been stable. Non-compliance yielded symptomatic relapse; restored compliance re-achieved symptomatic remission. CONCLUSIONS: Different MCAS presentations reflect elaboration of different mediators, some of which can induce inflammation and fibrosis. Thus, MCAS may have directly and/or indirectly driven ScM in these patients. MCAS should be considered in ScM presenting with comorbidities better explained by mast cell mediator release.     

凋亡细胞体外抑制T细胞活化

目的：研究凋亡细胞对Ｔ细胞活化的影响。方法：以ＣｏｎＡ刺激小鼠脾细胞增殖体系为研究对象,观察凋亡细胞预处理后对ＣｏｎＡ刺激的脾细胞ＣＤ６９表达的影响。结果：凋亡细胞可以抑制Ｔ细胞活化,而活细胞或坏死细胞却不能。同时抑制效果与凋亡种类诱导方式无关,而与凋亡细胞数量密切相关。结论：研究证明了凋亡细胞可以主动抑制Ｔ细胞活化,这一发现拓宽了目前对凋亡的认识,表明凋亡细胞主动调节免疫反应在一些生命的基本现象     

Mast cell functions in the innate skin immune system

Mast cells are not only potent effector cells in allergy, but are also important players in protective immune responses against pathogens. Most of our knowledge about mast cells in innate immunity is derived from models of sepsis, whereas their role in innate immune responses of the skin has largely been neglected in the past. Their particular pattern of distribution in the skin and their ability to sense and react to pathogens and other danger signals indicate that mast cells can be important sentinels and effector cells in skin immune responses. The recent findings reviewed here have confirmed this hypothesis and have established a prominent role for skin mast cells in innate immunity.     

天花粉蛋白对肥大细胞脱颗粒和组胺释放的影响及其与补体激活的关系

我们首先用Alcian蓝染色的肥大细胞脱颗粒试验和用荧光测定组胺的方法观察了天花粉蛋白对肥大细胞脱颗粒和组胺释放的影响。实验结果表明:(1)在体外试验中,不论有无血清的存在,天花粉蛋白都不引起肥大细胞的脱粒和组胺释放。(2)天花粉蛋白的体内用药,能引起Balb/c小鼠炎症局部的肥大细胞脱颗粒(Alcian着色的未脱颗粒肥大细胞由对照组的3.4±0.12×10~4/ml减少至1.7±0.28×10~4/l;P<0.01)和组胺水平的明显增高(皮下气囊内的组胺水平由36.39±0.94ng/ml升至41.07±0.78ng/ml;P<0.01)。(3)腹膜腔内注射天花粉蛋白后,Wistatr大鼠腹膜腔内蛋白明显渗出,同时全血组胺水平也明显增高(对照组:0.947±0.076ng/ml,实验组:1.574±0.105ng/ml;p<0.01)。(4)上述天花粉蛋白诱导的腹腔渗出液具有明显的肥大细胞脱颗粒作用(脱粒指数:对照组为1.6±3.8%,实验组为24.9±2.1%;P<0.01)。(5)用眼镜蛇毒素完全耗竭小鼠的补体对天花粉蛋白引起的肥大细胞脱粒因子的产生无明显影响。从这些结果可见:天花粉蛋白的体内应用能通过激活某些可溶性成分的产生而引起肥大细胞的脱颗粒和组胺释放。但是,这一过程与天花粉蛋白激活补体的作用似无明显关系。     

Mast cell heterogeneity: Evidence and implications

Mast cells and basophils play a fundamental role in the pathogenesis of allergic disease, although their physiologic role is largely unknown. A large body of evidence now indicates that the properties of mast cells are dependent on the tissue and species from which they are derived. Such mast cell heterogeneity encompasses differences in morphology, development, cytochemistry, and function. The evidence for such heterogeneity, and some of its clinical implications, is discussed.     

Responsiveness of human skin mast cells to repeated activation: an in vitro study

To assess human mast-cell (MC) behavior after repetitive activation, we cocultured human foreskin MC (SMC) with human foreskin fibroblasts (F). Under these conditions, we have previously demonstrated that SMC keep their viability and functional activity for up to 8 days. SMC were presensitized with atopic serum and repeatedly activated by consecutively increasing concentrations of anti-IgE antibodies (α-IgE, 0.0002–0.1). This treatment, which mimics the "rush desensitization" procedure, led to complete SMC unresponsiveness to activation by a-IgE at optimal concentrations, as evaluated by histamine release. However, presensitization of SMC with IgE antibodies before exposure to α-IgE restored their sensitivity to this stimulus. These data indicate that desensitization was probably due to lack of membrane-bound IgE rather than to downregulation of intracellular mechanisms. In fact, SMC challenged by an optimal concentration of α-lgE could release histamine upon a second activation by 2 h after the first activation, if the cells had been presensitized before the second challenge. SMC incubation with increasing concentrations of compound 48/80 (0.2–10μg/ml) led to MC unresponsiveness to an optimal concentration of this stimulus. Furthermore, SMC activated by an optimal concentration of compound 48/80 and rechallenged with the same agent were insensitive to the second activation for at least 24 h. In summary, we have shown that it is possible to induce "desensitization" in SMC to both IgEdependent and IgE-independent stimuli by incubating the cultures with consecutively increasing concentrations of the activator. SMC can release histamine when reactivated with a-IgE antibodies after presensitization by 2 h after the first challenge, while they reacquire their susceptibility to reactivation with compound 48/80 in only 2–3 days.     

Is There a Functional Heterogeneity among IgE-Type Mast Cell-Sensitizing Antibodies?

It has recently been established that mast cells display functional heterogeneity. The question then arises whether the IgE-type of antibody, which avidly binds to and thereby sensitizes mast cells and basophils for allergen-induced release of mediators, also expresses functional heterogeneity. In the present article we bring together several experimental observations, mainly from the rat system, which are difficult to explain unless one postulates that mast cell/basophil-sensitizing antibodies of the IgE-type are heterogeneous in their cell-binding properties.     

Mast cell tryptase in dermal neurogenic inflammation

BACKGROUND AND AIMS: Eosinophils, mast cells and T lymphocytes are important cells in the allergic inflammatory process. These cells produce and are regulated by cytokines such as interleukin-3 (IL-3), interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF). We initiated this study to evaluate pathological abnormalities and to detect IL-5 in the duodenal mucosa from patients with food allergy. METHODS: Endoscopy duodenal biopsy specimens were obtained from seven food-allergic patients, six atopic healthy controls and six nonatopic healthy controls. IL-5 protein was evaluated by immunohistochemistry. Electron microscopy as well as double immunofluorescent staining were used to identify the labelled cells and to localize IL-5. IL-5 mRNA expression was evaluated by qualitative polymerase chain reaction. RESULTS: A significantly increased number of lymphocytes, mast cells and eosinophils was detected in the lamina propria in food-allergic patients and, in lower number, in atopic controls. Immunostaining for IL-5 was markedly positive in food-allergic patients, slightly increased in atopic controls and negative in nonatopic controls. Ultrastructurally, in food-allergic patients and in atopic controls, IL-5 was localized in eosinophil granules, in the matrix of intact granules and at the periphery of altered granules. Double immunofluorescent staining was performed in food-allergic patients and showed that 86.7% of IL-5+ cells were eosinophils, and that IL-5 was expressed by 24% of eosinophils. IL-5 mRNA was expressed in food-allergic patients but was not detected in atopic and nonatopic controls. CONCLUSION: Activated eosinophils are involved in gut atopic reactions occurring in food allergy and are probably in part upregulated by their own local production of IL-5.