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Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI.

Iwamoto T, Hirai H, Yamaguchi N, Kobayashi N, Sugimoto H, Tabata T, Okuda M - Cancer Sci. (2014)

Bottom Line: This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity.On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05).In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Mie University Hospital, Mie University Graduate School of Medicine, Tsu, Japan; Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Japan.

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Binding levels of CRA1, CRA2, and anti-IgE antibody measured by basophil staining to confirm the passive sensitization by flow cytometric analysis. (a) Immunostained healthy subject's basophils with anti-FcεRI antibodies; PBMCs with or without acid treatment were stained for CD3, prostaglandin D2 receptor (CRTH2), and FcεRI. (b) Immunostained healthy subject's basophils with anti-IgE antibody; PBMCs with or without acid treatment were stained for CD3, CRTH2, and IgE. Flow cytometer charts for CD3− PBMCs are shown. Basophil fraction (CD3− and CRTH2+ PBMC) was gated. MFIs indicated for binding levels of anti-CRA1, anti-CRA2, and anti-IgE antibodies on basophils. MFI, mean fluorescence intensity.
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fig02: Binding levels of CRA1, CRA2, and anti-IgE antibody measured by basophil staining to confirm the passive sensitization by flow cytometric analysis. (a) Immunostained healthy subject's basophils with anti-FcεRI antibodies; PBMCs with or without acid treatment were stained for CD3, prostaglandin D2 receptor (CRTH2), and FcεRI. (b) Immunostained healthy subject's basophils with anti-IgE antibody; PBMCs with or without acid treatment were stained for CD3, CRTH2, and IgE. Flow cytometer charts for CD3− PBMCs are shown. Basophil fraction (CD3− and CRTH2+ PBMC) was gated. MFIs indicated for binding levels of anti-CRA1, anti-CRA2, and anti-IgE antibodies on basophils. MFI, mean fluorescence intensity.

Mentions: We tested the involvement of CBDCA-specific IgE on CBDCA-induced severe HR using in vitro sensitization. Dissociation of IgE from the basophils from the healthy basophil donor as well as binding of IgE to the basophils in CBDCA patients' plasma were confirmed either by staining with anti-FcεRI antibodies, CRA1 or CRA2, or with an anti-IgE antibody. As has already been shown, CRA1 reacts with a region other than the IgE binding site, whereas CRA2 reacts directly with the IgE binding site.(18) We were thus able to confirm the successful dissociation of IgE by confirming that acid treatment increased CRA2 staining levels (Fig. 2a). After passive sensitization, CRA2 staining levels decreased, thereby suggesting that IgE-dissociated FcεRI on the acid-treated basophils was occupied by IgE in patient plasma (Fig. 2a). Consistent with the results of the CRA2 staining, the level of IgE on basophils decreased after acid treatment, and increased after passive sensitization (Fig. 2b).


Carboplatin-induced severe hypersensitivity reaction: role of IgE-dependent basophil activation and FcεRI.

Iwamoto T, Hirai H, Yamaguchi N, Kobayashi N, Sugimoto H, Tabata T, Okuda M - Cancer Sci. (2014)

Binding levels of CRA1, CRA2, and anti-IgE antibody measured by basophil staining to confirm the passive sensitization by flow cytometric analysis. (a) Immunostained healthy subject's basophils with anti-FcεRI antibodies; PBMCs with or without acid treatment were stained for CD3, prostaglandin D2 receptor (CRTH2), and FcεRI. (b) Immunostained healthy subject's basophils with anti-IgE antibody; PBMCs with or without acid treatment were stained for CD3, CRTH2, and IgE. Flow cytometer charts for CD3− PBMCs are shown. Basophil fraction (CD3− and CRTH2+ PBMC) was gated. MFIs indicated for binding levels of anti-CRA1, anti-CRA2, and anti-IgE antibodies on basophils. MFI, mean fluorescence intensity.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4462369&req=5

fig02: Binding levels of CRA1, CRA2, and anti-IgE antibody measured by basophil staining to confirm the passive sensitization by flow cytometric analysis. (a) Immunostained healthy subject's basophils with anti-FcεRI antibodies; PBMCs with or without acid treatment were stained for CD3, prostaglandin D2 receptor (CRTH2), and FcεRI. (b) Immunostained healthy subject's basophils with anti-IgE antibody; PBMCs with or without acid treatment were stained for CD3, CRTH2, and IgE. Flow cytometer charts for CD3− PBMCs are shown. Basophil fraction (CD3− and CRTH2+ PBMC) was gated. MFIs indicated for binding levels of anti-CRA1, anti-CRA2, and anti-IgE antibodies on basophils. MFI, mean fluorescence intensity.
Mentions: We tested the involvement of CBDCA-specific IgE on CBDCA-induced severe HR using in vitro sensitization. Dissociation of IgE from the basophils from the healthy basophil donor as well as binding of IgE to the basophils in CBDCA patients' plasma were confirmed either by staining with anti-FcεRI antibodies, CRA1 or CRA2, or with an anti-IgE antibody. As has already been shown, CRA1 reacts with a region other than the IgE binding site, whereas CRA2 reacts directly with the IgE binding site.(18) We were thus able to confirm the successful dissociation of IgE by confirming that acid treatment increased CRA2 staining levels (Fig. 2a). After passive sensitization, CRA2 staining levels decreased, thereby suggesting that IgE-dissociated FcεRI on the acid-treated basophils was occupied by IgE in patient plasma (Fig. 2a). Consistent with the results of the CRA2 staining, the level of IgE on basophils decreased after acid treatment, and increased after passive sensitization (Fig. 2b).

Bottom Line: This did not occur when the same experiment was carried out using plasma from the patients negative for carboplatin hypersensitivity.On further investigation, the HR-positive group had significantly higher levels of FcεRI compared with the negative group (P < 0.05).In conclusion, an IgE-dependent mechanism incorporating FcεRI overexpression participates in carboplatin-induced severe HR.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Mie University Hospital, Mie University Graduate School of Medicine, Tsu, Japan; Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Japan.

Show MeSH
Related in: MedlinePlus