Positive Atopy Patch Test Reaction to Malassezia furfur in Atopic Dermatitis Correlates with a T Helper 2-like Peripheral Blood Mononuclear Cells Response

Johansson, Catharina; Eshaghi, Hojjat; Linder, Maria Tengvall; Jakobson, Eva; Scheynius, Annika

doi:10.1046/j.1523-1747.2002.01758.x

Cited by 70 publications

(44 citation statements)

References 38 publications

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“…However, in that study the possible association with allergen-specific IgE was not considered. Later we showed a significantly higher M. sympodialis -specific proliferation and a Th2-like cytokine response in PBMC from ATP-positive versus APT-negative patients (with both patient groups having elevated levels of allergen-specific IgE) [26]. Moreover, in a study to explore the relevance of an in vivo topical challenge method for house dust mite hypersensitivity, Shah et al [27] found that the same 30% of adult IgE+ AE patients that revealed eczema upon in vivochallenge also responded with significantly higher PBMC proliferation upon in vitro allergen challenge.…”

Section: Discussionmentioning

confidence: 99%

Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction

Johansson

Ahlborg

Andersson

et al. 2009

Int Arch Allergy Immunol

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Background: Atopic eczema is a chronic inflammatory skin disease in which several subgroups of cases can be identified. Atopy patch testing (APT) reveals allergen sensitization also in atopic eczema patients devoid of detectable allergen-specific IgE, suggesting the importance of factors other than IgE in the reaction. Here we investigate the relationship between APT reactions and allergen-specific peripheral IgE and T cell reactivity in atopic eczema patients. Methods: Adult patients with atopic eczema (n = 64) and healthy controls (n = 24) were analyzed for reactivity to Malassezia sympodialis extract by APT, measurement of specific plasma IgE and in vitro determination of the frequency of allergen-reactive peripheral blood mononuclear cells producing interleukin-4 and interleukin-5 using the ELISpot method. Results: When combining the results of the APT, IgE measurements and the ELISpot analyses, reactivity to M. sympodialis was found in a majority of the atopic eczema patients (69%), whereas the healthy controls were negative throughout. T cell reactivity to M. sympodialis, manifested by production of both interleukins 4 and 5, was highly predictive for a positive APT reaction and displayed a strongly positive correlation with the APT score. In contrast, the allergen-specific IgE levels did not predict the APT outcome, and no correlation could be found between the IgE levels and the APT score. Conclusion: Peripheral allergen-specific T helper 2 cell-mediated reactivity appears to be required for a positive APT reaction to M. sympodialis. The diagnostic potential of measuring peripheral allergen-specific T cell responses should be considered in atopic eczema.

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Section: Discussionmentioning

confidence: 99%

Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction

Johansson

Ahlborg

Andersson

et al. 2009

Int Arch Allergy Immunol

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“…That finding strongly supports that the T-cell response is another crucial factor for allergen-specific eczema reactions in AE in addition to antigen presentation mediated by specific IgE bound to epidermal Langerhans cells [36, 37]. The lack of positive APT reactions to Malassezia in certain AE patients with serum IgE reactivity to Malassezia may rather be explained by low levels of Malassezia -specific Th2-like T cells [8]than by the blocking of IgG4 antibodies.…”

Section: Discussionmentioning

confidence: 53%

“…We have previously shown that positive APT reactions to Malassezia have a stronger correlation to a Th2-like T-cell response than to elevated levels of Malassezia- specific serum IgE [8]. That finding strongly supports that the T-cell response is another crucial factor for allergen-specific eczema reactions in AE in addition to antigen presentation mediated by specific IgE bound to epidermal Langerhans cells [36, 37].…”

Section: Discussionmentioning

confidence: 68%

“…In a study on the response of peripheral blood mononuclear cells to Malassezia we showed a correlation between a Th2-like T-cell response and positive APT reactions, which was significantly more pronounced than the correlation between serum IgE and positive APT reactions [8]. The association between T-cell-mediated allergen-specific responses and positive APT reactions has also been demonstrated by others [9].…”

Section: Introductionmentioning

confidence: 53%

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Elevated Levels of IgG and IgG4 to <i>Malassezia</i> Allergens in Atopic Eczema Patients with IgE Reactivity to<i> Malassezia</i>

Johansson

Linder²,

Aalberse

et al. 2004

Int Arch Allergy Immunol

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Background: The opportunistic yeast Malassezia is considered to be one of the factors that can contribute to atopic eczema (AE). Elevated serum IgE levels, T-cell proliferation and positive skin prick test (SPT) and atopy patch test (APT) reactions to Malassezia are found among AE patients. Methods: Sera from 127 AE patients, 14 patients with seborrheic dermatitis (SD) and 33 healthy controls were investigated for IgE and IgG4 to M. sympodialis extract and four recombinant Malassezia allergens; rMala s 1, rMala s 5, rMala s 6, and rMala s 9. In addition, IgG to the recombinant allergens was analyzed. The IgG and IgG4 levels were compared to IgE levels and in vivo reactions (SPT and APT) to Malassezia. Results: AE patients with serum IgE levels >0.35 kU/l to M. sympodialis extract had significantly higher IgG4 levels to M. sympodialis extract than AE patients without detectable serum IgE to M. sympodialis extract, SD patients and healthy controls. Among the AE patients with and without detectable serum IgE to M. sympodialis extract, respectively, there were no differences in IgG4 levels between patients with positive or negative in vivo reactions to M. sympodialis extract. IgG4 to the rMala s allergens was almost exclusively found among patients with IgE to the same allergen. Within the four tested rMala s allergens, most IgG4 reactions were found to rMala s 6, an allergen with homology to cyclophilin. Conclusions: Elevated serum IgG4 to M. sympodialis extract accompanies elevated serum IgE to the extract. This is further confirmed by the association between IgG/IgG4 and IgE to recombinant Malassezia allergens.

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“…The concentrations encountered by mast cells in vivo can only be estimated. However, the extract concentrations used in this study concord with amounts used for atopy patch tests (41) and for in vitro activation of human T cells (42,43). Even if the concentration of M. sympodialis that reaches the IgE receptor cross-linked mast cells in the skin along with other allergens is not sufficient to increase mast cell degranulation, it might still result in IL-6 release, thus enabling an increased Th2 differentiation and thereby promoting allergic inflammation.…”

Section: Discussionmentioning

confidence: 82%

TLR2/MyD88-Dependent and -Independent Activation of Mast Cell IgE Responses by the Skin Commensal Yeast Malassezia sympodialis

Selander

Engblom

Nilsson

et al. 2009

The Journal of Immunology

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Atopic eczema (AE) is a chronic inflammatory skin disease. Approximately 50% of adult AE patients have allergen-specific IgE reactivity to the skin commensal yeast Malassezia spp. Due to the ruptured skin barrier in AE, it is likely that Malassezia can come into contact with mast cells, which are known to be involved in AE. We therefore hypothesized that Malassezia spp. can activate mast cells. Bone marrow-derived mast cells (BMMCs) were generated from wild type, TLR2, TLR4, and MyD88 gene-deleted mice and cocultured with Malassezia sympodialis extract. We recorded that M. sympodialis induced release of cysteinyl leukotrienes in a dose-dependent manner in nonsensitized and IgE-anti-trinitrophenyl-sensitized BMMCs, respectively, with three times higher levels in the latter type of cells. IgE-sensitized BMMCs also responded by degranulation as assessed by release of β-hexosaminidase, increased MCP-1 production through a MyD88-independent pathway, and activated phosphorylation of the MAPK ERK1/2. Furthermore, M. sympodialis enhanced the degranulation of IgE receptor cross-linked wild-type BMMCs and altered the IL-6 release dose-dependently. This degranulation was independent of TLR2, TLR4, and MyD88, whereas the IL-6 production was dependent on the TLR2/MyD88 pathway and MAPK signaling. In conclusion, M. sympodialis extract can activate nonsensitized and IgE-sensitized mast cells to release inflammatory mediators, to enhance the IgE-mediated degranulation of mast cells, and to modulate MAPK activation and by signaling through the TLR2/MyD88 pathway to modify the IL-6 production of IgE receptor cross-linked mast cells. Collectively, these findings indicate that M. sympodialis can activate mast cells and might thus exacerbate the inflammatory response in AE.

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Positive Atopy Patch Test Reaction to Malassezia furfur in Atopic Dermatitis Correlates with a T Helper 2-like Peripheral Blood Mononuclear Cells Response

Cited by 70 publications

References 38 publications

Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction

Elevated Peripheral Allergen-Specific T Cell Response Is Crucial for a Positive Atopy Patch Test Reaction

Elevated Levels of IgG and IgG4 to <i>Malassezia</i> Allergens in Atopic Eczema Patients with IgE Reactivity to<i> Malassezia</i>

TLR2/MyD88-Dependent and -Independent Activation of Mast Cell IgE Responses by the Skin Commensal Yeast Malassezia sympodialis

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