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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent advances in our understanding of mast cell biology and disease resulted in identification of important differences in expression of mast cell surface antigens in normal and neoplastic mast cells. Most notably, detection of aberrant expression of CD25 and CD2 on the surface of neoplastic mast cells but not on their normal counterparts leads to the inclusion of this immunophenotypic abnormality in the World Health Organization's diagnostic criteria for systemic mastocytosis. Aberrant mast cell surface marker expression can be detected in the bone marrow aspirate by flow cytometry, even in patients with limited disease that lacks histopathologically detectable aggregates of mast cells in bone marrow biopsy sections. Flow cytometric analysis of bone marrow mast cells is therefore a sensitive method of diagnosis of mast cell disease and is expected to find increasing use in determining response to emerging mast cell cytoreductive therapies.
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PMID:Urticaria pigmentosa and mastocytosis: the role of immunophenotyping in diagnosis and determining response to treatment. 1682 80

A case of a 70-year-old man presenting with exsudative enteropathy due to light-chain-associated amyloidosis is reported. The diagnosis of systemic mastocytosis associated with IgG/lambda plasma cell myeloma and secondary generalised amyloidosis was carried out by morphological evaluation of bone marrow biopsy. The c-kit point mutation D816Y was detected by molecular analysis. Two years before, a cystadenolymphoma of the left parotid gland had been removed. A moderate increase of loosely scattered spindle-shaped mast cells, a subpopulation of them expressing CD25, an antigen that is not expressed by normal or reactive mast cells, was shown by retrospective analysis carried out on an intraparotideal lymph node. The c-kit mutation D816Y was shown by the molecular analysis of the lymph node. In summary, the notion that systemic mastocytosis may very rarely be associated with B cell neoplasms and that neoplastic mast cell infiltrates may be obscured because of only a minimal increase of atypical mast cells, which are outnumbered by other non-neoplastic cells in the same tissue, is supported by this case. This finding was preliminarily termed "occult" mastocytosis.
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PMID:"Occult" mastocytosis with activating c-kit point mutation evolving into systemic mastocytosis associated with plasma cell myeloma and secondary amyloidosis. 1687 65

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.
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PMID:Mastocytosis: state of the art. 1758 83

Hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), and mast cell disease (MCD) are all considered myeloproliferative neoplasms, and diagnosis in each instance requires bone marrow examination with cytogenetic and molecular studies. HES should be distinguished from both molecularly defined and otherwise uncategorized CEL. The genes that are mutated in molecularly defined CEL include those that encode for platelet-derived growth factor receptors A and B and for fibroblast growth factor receptor 1. Diagnosis of MCD is facilitated by tryptase immunostaining and immunophenotyping to detect abnormal CD25-positive mast cells. Mutation screening for KITD816V is also advised but is not essential for the diagnosis of MCD. Asymptomatic patients with HES and no evidence of organ damage do not necessarily require immediate therapy. The same is true for patients with indolent MCD. At present, effective cytoreductive drugs for HES include corticosteroids, interferon-alpha (IFN-alpha), and hydroxyurea, imatinib for platelet-derived growth factor receptor A or B-rearranged CEL imatinib, and for MCD IFN-alpha and cladribine. In addition, a number of new drugs are currently being tested for their safety and efficacy in all 3 disorders.
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PMID:Hypereosinophilic syndrome, chronic eosinophilic leukemia, and mast cell disease. 1803 76

The WHO has published an updated classification of mastocytosis and the criteria for the diagnosis of systemic mastocytosis (SM). These include one major criterion, compact mast cell (MC) infiltrates in extracutaneous tissues, and four minor criteria, i.e. cytomorphologic atypia with spindling of MC (>25 %), detection of the activating somatic c-kit mutation D816 V in MC, aberrant expression of CD2 and/or CD25 on MC, and an elevated serum tryptase level (>20 ng/ml). Systemic mastocytosis is diagnosed when the major plus one minor, or three minor criteria are fulfilled. In the present study, we have established methods for the detection of CD25 and the c-kit mutation D816V in paraffin-embedded bone marrow trephine biopsy specimen of 57 patients with various subtypes of mastocytoses and 239 controls. While MCs in almost all patients with SM (55/57) expressed CD25, only 2/239 of the control samples contained CD25-positive MCs. With newly designed molecular pathological methods, c-kit codon 816 mutations were detected by "peptide nucleic acid" (PNA)-mediated PCR-clamping and/or analysis of microdissected MC in 52/57 cases with SM. All cases with detectable c-kit mutations also contained CD25-positive MC. The c-kit mutation D816 V was also detected in microdissected cells of associated hematologic neoplasias in 6/15 cases. With the methods established for the investigation of paraffine-embedded tissues, the pathologist plays a central role in the diagnosis of SM.
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PMID:[Immunohistochemical and molecular characterization of systemic mastocytoses]. 1803 98

Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous mastocytosis [urticaria pigmentosa (UP)], and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.
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PMID:Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. 1805 23

Urticaria pigmentosa (UP) is a clinicopathologic term used to describe reddish-brown cutaneous macules and papules, characterized histologically by mast cell infiltration of the papillary and upper reticular dermis and reactive basal hyperpigmentation of the overlying epidermis. Although typically a benign, self-limited disorder of childhood, a significant proportion (up to 30%) of adolescent and adult-onset UP represents cutaneous involvement by underlying systemic mastocytosis (SM). Predicting the course of cutaneous mast cell disease has been limited by a lack of diagnostic and prognostic markers. In patients with SM, neoplastic bone marrow mast cells show aberrant surface expression of CD25. However, whether CD25 expression on cutaneous mast cells is associated with underlying SM is unknown. In this study, we performed a clinicopathologic analysis of 30 adult patients presenting with UP between 1987 and 2007. Cutaneous mast cell infiltration pattern, cytomorphology, density, and CD25 immunoreactivity were correlated with underlying or subsequent SM. On the basis of clinical and pathologic follow-up, 10 of 30 (33%) patients were diagnosed with SM and 20 of 30 (67%) with limited cutaneous mastocytosis (CM). Although cutaneous mast cell density was slightly higher in patients with SM compared to those with limited CM (P=0.047), neither mast cell cytomorphology nor infiltration pattern correlated with underlying systemic disease. However, cutaneous mast cells from all 10 patients with SM (100%) were immunoreactive for CD25, compared to only 5 of 20 (25%) with limited CM (P<0.001). Our findings suggest that immunoreactivity for CD25 in cutaneous mast cells may be useful for stratifying adult patients presenting with UP for additional clinical evaluation.
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PMID:CD25 expression on cutaneous mast cells from adult patients presenting with urticaria pigmentosa is predictive of systemic mastocytosis. 1816 81

Mast cell activation is associated with atopic and inflammatory diseases, but the natural controls of mast cell homeostasis are poorly understood. We hypothesized that CD4(+)CD25(+) regulatory T cells (Treg) could function in mast cell homeostasis. In this study, we demonstrate that mast cells can recruit both Treg and conventional CD4(+) T cells (Tconv). Furthermore, Treg, but not Tconv, suppress mast cell FcepsilonRI expression. Despite the known inhibitory functions of IL-10 and TGFbeta1, FcepsilonRI suppression was independent of IL-10 and TGF-beta1 and required cell contact. Surprisingly, coculture with either Treg or Tconv cells suppressed IgE-mediated leukotriene C(4) production but enhanced cytokine production by mast cells. This was accompanied by a selective increase in FcepsilonRI-mediated Stat5 phosphorylation, which is a critical mediator of IgE-mediated cytokine secretion. These data are the first direct demonstration that mast cells can recruit Treg and illustrate that T cell interactions can alter the mast cell response.
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PMID:Cutting edge: CD4 T cell-mast cell interactions alter IgE receptor expression and signaling. 1825 Apr 8

Patients with systemic mastocytosis (SM) may acquire an associated hematologic non-mast cell (MC)-lineage disease (AHNMD). In most cases, a myeloid neoplasm is diagnosed, whereas the occurrence of a lymphoproliferative disease is an extremely rare event. We report on a patient with indolent SM associated with small lymphocytic lymphoma (SLL). The patient presented with lymphadenopathy, maculopapular exanthema, and elevated serum tryptase. The bone marrow biopsy showed focal MC aggregates together with SLL. As assessed by immunostaining, neoplastic MC were found to exhibit CD117 and CD25 but did not display CD5 or CD20, whereas SLL cells were found to coexpress CD5 and CD20 but did not express MC antigens. The KIT mutation D816V was detected in sorted CD34(+) cells and unfractionated marrow cells but not in CD5(+) SLL cells, confirming the coexistence of 2 distinct neoplasms.
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PMID:Indolent systemic mastocytosis associated with atypical small lymphocytic lymphoma: a rare form of concomitant lymphoproliferative disease. 1844 46

Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette-Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4(+) CD25(+) Foxp3(+) T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4(+) CD25(+) T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-beta (TGF-beta)-producing CD4(+) CD25(+) Foxp3(+) regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma.
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PMID:Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCG. 1919 2


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