Microscopic Morphology of Different Types of Urticaria

Haas, Norbert; Toppe, Esdert; Henz, Beate M.

doi:10.1001/archderm.134.1.41

Cited by 103 publications

(82 citation statements)

References 39 publications

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“…The latter possibility is of particular interest because some patients with chronic urticaria have basopenia [13]and their hyporesponsiveness to anti-IgE suggests in vivo desensitization [14]. Although migration of basophils into the skin of patients has been suggested as an explanation for these observations, there is no evidence of basophil accumulation within the skin [15, 16, 17]nor is there evidence of basopenia in allergic rhinitis or asthma where migration from the blood into involved tissue has been demonstrated to be a concomitant of the late phase reaction. In this manuscript we demonstrate elevated IL-4 levels in plasma of patients with chronic urticaria.…”

Section: Discussionmentioning

confidence: 99%

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Ferrer¹,

Luquin²,

Sánchez-Ibarrola³

et al. 2002

Int Arch Allergy Immunol

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Background: Approximately 35–40% of patients with chronic urticaria have an IgG autoantibody to the IgE receptor which can activate basophils and mast cells so that they release histamine. In this study we assessed the cytokine profile present in chronic urticaria sera, and then measured cytokine and leukotriene release from basophils and mast cells upon incubation with chronic urticaria sera. Finally we assessed cytokine expression at the single-cell level and characterized the T cell subpopulations involved in their production. We chose IL-4 as representative of Th2 lymphocytes and IFN-γ for Th1 lymphocytes. Methods: We analyzed IL-4, IL-5 and IFN-γ in 60 chronic urticaria sera versus 51 controls. Sera were incubated with purified human basophils and cutaneous mast cells and the release of histamine, IL-4 and leukotrienes (C₄, D₄, E₄) was quantitated. Immunoblotting was performed to identify IgG antibody to FcΕRIα, α subunit. We measured intracellular cytokine production in peripheral blood mononuclear cells of 17 chronic urticaria patients compared to 50 healthy controls. Results: We found higher IL-4 levels (p = 0.028) in the sera of chronic urticaria patients (1.03 pg/ml) versus healthy donors (0.20 pg/ml) but no difference between urticaria sera and atopic control sera (0.52 pg/ml). We did not detect IFN-γ or IL-5 in any serum. However, sera that activated basophils so that they released histamine also produced leukotriene and IL-4, and leukotriene production by cutaneous mast cells and basophils was closely correlated. However, there was no correlation between immunoblotting and the functional ability to induce either histamine or IL-4. After stimulating with PMA-ionomycin we found significant differences in CD4+ lymphocyte production of IL-4 and IFN-γ with no differences in CD8+ lymphocyte production of either cytokine. Conclusion: Our data support the presence of basophil and mast cell activators in the sera of patients with chronic urticaria which can lead to the production of leukotrienes and IL-4 in addition to the histamine. IL-4 levels are similar to those seen in atopic subjects. We found that CD4+ T cells from patients with chronic urticaria are activated and tend to produce higher cytokine levels than CD4+ T cells from healthy controls. There were no differences when cytokine production by CD8+ lymphocytes was similarly assessed. These results are consistent with the histology found in biopsies of chronic urticaria lesions, where a CD4+-predominant infiltrate is found with cytokine production suggesting either a Th0 response or a mixture of Th1 and Th2 lymphocytes.

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Section: Discussionmentioning

confidence: 99%

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Ferrer¹,

Luquin²,

Sánchez-Ibarrola³

et al. 2002

Int Arch Allergy Immunol

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“…36,37 Before exposure to antibodies, antigen unmasking was performed by incubating the skin sections in a commercial antigen retrieval buffer (pH 9.9) (Target Retrieval Solution; DakoCytomation, Hamburg, Germany) for 30 minutes at 95°C. Immunoreactivity for bcl-2 and bcl-xL was then investigated using a mouse anti-human bcl-2 mAb (clone 100/ D5; dilution 1:100; Zymed Laboratories, South San Francisco, CA), a mouse anti-human bcl-xL mAb (clone 7B2.5; dilution 1:500; DPC Biermann, Bad Nauheim, Germany), and the alkaline phosphatase anti-alkaline phosphatase (APAAP) technique.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Hartmann

Artuc

Baldus

et al. 2003

The American Journal of Pathology

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Mastocytosis is a rare disease characterized by accumulation of mast cells in tissues.To investigate whether an altered regulation of mast cell apoptosis might be involved in the pathogenesis of mastocytosis, expression of the apoptosis-preventing molecules bcl-2 and bcl-xL was studied by immunohistochemistry in skin and bone marrow lesions of mastocytosis patients. In addition, reverse transcription-polymerase chain reaction was used to investigate levels of bcl-2 and bcl-xL mRNA in cutaneous mastocytosis lesions. Since activating mutations of c-kit are known to be associated with some forms of mastocytosis, human mast cell cultures were also stimulated via c-kit and the expression of bcl-2 and bcl-xL was assessed by immunoblotting. In patients with mastocytosis, the expression of bcl-2 protein but not bcl-xL in cutaneous mast cells was significantly enhanced, compared to healthy controls. Evaluating different subgroups of adult and pediatric mastocytosis patients, all groups were found to express significantly increased levels of bcl-2 protein, and none of the patient groups was found to overexpress bcl-xL, with the exception of solitary mastocytomas that showed a tendency for up-regulated bcl-xL protein. Furthermore, the expression of bcl-2 mRNA was significantly enhanced in cutaneous lesions of adult and pediatric patients, while bcl-xL mRNA levels were only slightly increased in pediatric, but not in adult patients with mastocytosis. In contrast to the skin lesions, bone marrow infiltrates of patients with systemic mastocy- Mastocytosis represents a heterogeneous group of diseases characterized by an increase of mast cells in different organs.

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“…This may result either from mast cell activation or from a higher number of mast cells in the skin or elsewhere. Haas et al [13] report an increase in mast cells in lesional and non-lesional skin of CU patients with classical histochemical staining methods. However, recent studies that have used immunohistochemical techniques with specific monoclonal antibodies to mast cell tryptase have not confirmed these findings [6,21].…”

Section: Introductionmentioning

confidence: 99%

Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa

Minnei

Wetzels²,

Hertogh³

et al. 2005

Virchows Arch

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Chronic urticaria (CU) is characterized by recurrent itching skin eruptions caused by mast cell degranulation. Relapses can be provoked by food intake. The aim of this study was to investigate if the mast cell number in the gastroduodenal mucosa is increased in CU patients, and whether mast cell counting by pathologists is clinically useful. We defined two study groups: 50 disease controls (16 Belgians and 34 Italians) and 43 Belgian CU patients. Mast cells were detected using immunohistochemistry for tryptase and CD117. The mast cell number in the disease controls was 20.2/high-power filed (HPF; 133.3/mm2) in the stomach and 32.5/HPF (209.2/mm2) in the duodenum. There was no difference between Belgian and Italian controls, indicating that dietary habits have no influence on the normal gastroduodenal mast cell number. In CU patients, mast cell numbers were significantly higher: 32.4/HPF (186.0/mm2) in the stomach (P<0.0001) and 44.8/HPF (246.0/mm2) in the duodenum (P=0.0002). CU is thus associated with mast cell infiltration in the gastroduodenal mucosa, even if patients do not have gastrointestinal symptoms. Mast cell counting in gastroduodenal biopsies of CU patients can be useful in selecting patients who may respond to a therapy with intestinal mast-cell-stabilizing agents.

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Microscopic Morphology of Different Types of Urticaria

Cited by 103 publications

References 39 publications

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Expression of Bcl-2 and Bcl-xL in Cutaneous and Bone Marrow Lesions of Mastocytosis

Chronic urticaria is associated with mast cell infiltration in the gastroduodenal mucosa

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