Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism
Summary Background Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE‐mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable ph...
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| Veröffentlicht in: | Clinical and experimental allergy 2004-10, Vol.34 (10), p.1602-1609 |
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| creator | Hegde, V. L. Venkatesh, Y. P. |
| description | Summary
Background
Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE‐mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug).
Objective
The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol.
Methods
Methodology involved skin prick tests (SPTs), high‐performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++‐ion‐moderated cation‐exchange chromatography, preparation of alditol–protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on d‐mannitol–keyhole limpet haemocyanin (KLH)–Sepharose CL‐6B, and detection of serum mannitol‐specific IgE by ELISA.
Results
Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, d‐mannitol–bovine serum albumin and d‐mannitol–KLH showed positive weal/flare reaction, demonstrating the presence of cell‐bound mannitol‐specific IgE in vivo. Negative results with d‐glucitol, d‐galactitol, meso‐erythritol, and l‐mannitol protein conjugates clearly showed that the mannitol‐specific human IgE is very specific to the d‐isomer of mannitol. ELISA using the hapten affinity‐purified allergic serum was positive, demonstrating the presence of mannitol‐specific serum IgE in the allergic subject.
Conclusion
Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE‐mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol‐specific human IgE in a sensitized allergic subject to validate an IgE‐mediated hypersensitivity mechanism for mannitol. |
| doi_str_mv | 10.1111/j.1365-2222.2004.02079.x |
| format | Article |
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Background
Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE‐mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug).
Objective
The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol.
Methods
Methodology involved skin prick tests (SPTs), high‐performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++‐ion‐moderated cation‐exchange chromatography, preparation of alditol–protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on d‐mannitol–keyhole limpet haemocyanin (KLH)–Sepharose CL‐6B, and detection of serum mannitol‐specific IgE by ELISA.
Results
Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, d‐mannitol–bovine serum albumin and d‐mannitol–KLH showed positive weal/flare reaction, demonstrating the presence of cell‐bound mannitol‐specific IgE in vivo. Negative results with d‐glucitol, d‐galactitol, meso‐erythritol, and l‐mannitol protein conjugates clearly showed that the mannitol‐specific human IgE is very specific to the d‐isomer of mannitol. ELISA using the hapten affinity‐purified allergic serum was positive, demonstrating the presence of mannitol‐specific serum IgE in the allergic subject.
Conclusion
Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE‐mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol‐specific human IgE in a sensitized allergic subject to validate an IgE‐mediated hypersensitivity mechanism for mannitol.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2004.02079.x</identifier><identifier>PMID: 15479277</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Adult ; alditol-protein conjugates ; Allergens - immunology ; Allergic diseases ; anaphylaxis ; Anaphylaxis - blood ; Anaphylaxis - immunology ; Biological and medical sciences ; chemical allergy ; Chromatography, High Pressure Liquid - methods ; cisapride ; Cisapride - adverse effects ; Cisapride - immunology ; Enzyme-Linked Immunosorbent Assay - methods ; excipient ; Excipients - adverse effects ; Female ; food additive ; Food Additives - adverse effects ; Food Hypersensitivity - blood ; Food Hypersensitivity - immunology ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; hapten ; Humans ; Immunoglobulin E - blood ; Immunoglobulin E - immunology ; Immunopathology ; mannitol ; Mannitol - adverse effects ; Mannitol - immunology ; mannitol-BSA ; mannitol-specific IgE ; Medical sciences ; Punicaceae - adverse effects ; Punicaceae - immunology ; Skin Tests - methods ; Sorbitol - immunology ; Sugar Alcohols - immunology</subject><ispartof>Clinical and experimental allergy, 2004-10, Vol.34 (10), p.1602-1609</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Oct 2004</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5579-e02006e49cdbac2c5b9e818bdf2fb8e7b2ef123311d5749e8a12f860f87ddd633</citedby><cites>FETCH-LOGICAL-c5579-e02006e49cdbac2c5b9e818bdf2fb8e7b2ef123311d5749e8a12f860f87ddd633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2222.2004.02079.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2004.02079.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16173527$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15479277$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hegde, V. L.</creatorcontrib><creatorcontrib>Venkatesh, Y. P.</creatorcontrib><title>Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary
Background
Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE‐mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug).
Objective
The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol.
Methods
Methodology involved skin prick tests (SPTs), high‐performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++‐ion‐moderated cation‐exchange chromatography, preparation of alditol–protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on d‐mannitol–keyhole limpet haemocyanin (KLH)–Sepharose CL‐6B, and detection of serum mannitol‐specific IgE by ELISA.
Results
Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, d‐mannitol–bovine serum albumin and d‐mannitol–KLH showed positive weal/flare reaction, demonstrating the presence of cell‐bound mannitol‐specific IgE in vivo. Negative results with d‐glucitol, d‐galactitol, meso‐erythritol, and l‐mannitol protein conjugates clearly showed that the mannitol‐specific human IgE is very specific to the d‐isomer of mannitol. ELISA using the hapten affinity‐purified allergic serum was positive, demonstrating the presence of mannitol‐specific serum IgE in the allergic subject.
Conclusion
Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE‐mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol‐specific human IgE in a sensitized allergic subject to validate an IgE‐mediated hypersensitivity mechanism for mannitol.</description><subject>Adult</subject><subject>alditol-protein conjugates</subject><subject>Allergens - immunology</subject><subject>Allergic diseases</subject><subject>anaphylaxis</subject><subject>Anaphylaxis - blood</subject><subject>Anaphylaxis - immunology</subject><subject>Biological and medical sciences</subject><subject>chemical allergy</subject><subject>Chromatography, High Pressure Liquid - methods</subject><subject>cisapride</subject><subject>Cisapride - adverse effects</subject><subject>Cisapride - immunology</subject><subject>Enzyme-Linked Immunosorbent Assay - methods</subject><subject>excipient</subject><subject>Excipients - adverse effects</subject><subject>Female</subject><subject>food additive</subject><subject>Food Additives - adverse effects</subject><subject>Food Hypersensitivity - blood</subject><subject>Food Hypersensitivity - immunology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>hapten</subject><subject>Humans</subject><subject>Immunoglobulin E - blood</subject><subject>Immunoglobulin E - immunology</subject><subject>Immunopathology</subject><subject>mannitol</subject><subject>Mannitol - adverse effects</subject><subject>Mannitol - immunology</subject><subject>mannitol-BSA</subject><subject>mannitol-specific IgE</subject><subject>Medical sciences</subject><subject>Punicaceae - adverse effects</subject><subject>Punicaceae - immunology</subject><subject>Skin Tests - methods</subject><subject>Sorbitol - immunology</subject><subject>Sugar Alcohols - immunology</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1u1DAURi0EotPCKyALCXYJ_oljG4nFMJoWUAUboEvLcW6oh8SZxglk3h6HGbUSK-7Glu75rj4dhDAlOU3zZpdTXoqMpckZIUVOGJE6nx-h1f3iMVoRLYpMKl2cofMYd4QQLrR6is6oKKRmUq7Q93Ww-9tDa2cf8dhjmJ3fewgj7mwIfuzbtxh--RqCA9z0A7YB-66bQv-j7aup9QFvsw5qb0eocQfu1gYfu2foSWPbCM9P7wX6drn9uvmQXX-5-rhZX2dOCKkzSL1JCYV2dWUdc6LSoKiq6oY1lQJZMWgo45zSWsgi7SxljSpJo2Rd1yXnF-j18e5-6O8miKPpfHTQtjZAP0VDpeLpYJHAl_-Au34aQupmqNZKlwUnCVJHyA19jAM0Zj_4zg4HQ4lZxJudWfyaxa9ZxJu_4s2coi9O96cq6XgInkwn4NUJsNHZthlscD4-cCWVXLCFe3fkfvsWDv9dwGy26-WX8tkx7-MI833eDj9NKbkU5ubzleFUvWef1Mbc8D9_fq1z</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Hegde, V. L.</creator><creator>Venkatesh, Y. P.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>200410</creationdate><title>Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism</title><author>Hegde, V. L. ; Venkatesh, Y. P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5579-e02006e49cdbac2c5b9e818bdf2fb8e7b2ef123311d5749e8a12f860f87ddd633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adult</topic><topic>alditol-protein conjugates</topic><topic>Allergens - immunology</topic><topic>Allergic diseases</topic><topic>anaphylaxis</topic><topic>Anaphylaxis - blood</topic><topic>Anaphylaxis - immunology</topic><topic>Biological and medical sciences</topic><topic>chemical allergy</topic><topic>Chromatography, High Pressure Liquid - methods</topic><topic>cisapride</topic><topic>Cisapride - adverse effects</topic><topic>Cisapride - immunology</topic><topic>Enzyme-Linked Immunosorbent Assay - methods</topic><topic>excipient</topic><topic>Excipients - adverse effects</topic><topic>Female</topic><topic>food additive</topic><topic>Food Additives - adverse effects</topic><topic>Food Hypersensitivity - blood</topic><topic>Food Hypersensitivity - immunology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>hapten</topic><topic>Humans</topic><topic>Immunoglobulin E - blood</topic><topic>Immunoglobulin E - immunology</topic><topic>Immunopathology</topic><topic>mannitol</topic><topic>Mannitol - adverse effects</topic><topic>Mannitol - immunology</topic><topic>mannitol-BSA</topic><topic>mannitol-specific IgE</topic><topic>Medical sciences</topic><topic>Punicaceae - adverse effects</topic><topic>Punicaceae - immunology</topic><topic>Skin Tests - methods</topic><topic>Sorbitol - immunology</topic><topic>Sugar Alcohols - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hegde, V. L.</creatorcontrib><creatorcontrib>Venkatesh, Y. P.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hegde, V. L.</au><au>Venkatesh, Y. P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2004-10</date><risdate>2004</risdate><volume>34</volume><issue>10</issue><spage>1602</spage><epage>1609</epage><pages>1602-1609</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary
Background
Anaphylaxis to mannitol present naturally in pomegranate and cultivated mushroom in a sensitized subject has been described recently, and an IgE‐mediated mechanism to this sugar alcohol has been proposed. The same subject also experienced severe allergic reactions to a chewable pharmaceutical (cisapride drug).
Objective
The purpose of the study was to identify allergenic component in the pharmaceutical preparation, and also, to understand the mechanism of immediate hypersensitivity to mannitol.
Methods
Methodology involved skin prick tests (SPTs), high‐performance liquid chromatographic (HPLC) analysis of pharmaceutical preparations, separation of mannitol by Ca++‐ion‐moderated cation‐exchange chromatography, preparation of alditol–protein conjugates by reductive amination, SPT using the conjugates, hapten affinity purification of the allergic serum on d‐mannitol–keyhole limpet haemocyanin (KLH)–Sepharose CL‐6B, and detection of serum mannitol‐specific IgE by ELISA.
Results
Component testing by SPT, and HPLC analysis of various pharmaceuticals indicated that the excipient mannitol is the causative allergen. Mannitol separated from Cisapid MPS showed allergenic activity by SPT. Among the several conjugates tested by SPT, d‐mannitol–bovine serum albumin and d‐mannitol–KLH showed positive weal/flare reaction, demonstrating the presence of cell‐bound mannitol‐specific IgE in vivo. Negative results with d‐glucitol, d‐galactitol, meso‐erythritol, and l‐mannitol protein conjugates clearly showed that the mannitol‐specific human IgE is very specific to the d‐isomer of mannitol. ELISA using the hapten affinity‐purified allergic serum was positive, demonstrating the presence of mannitol‐specific serum IgE in the allergic subject.
Conclusion
Mannitol, which is widely used as a food and drug additive (excipient), can rarely cause IgE‐mediated anaphylaxis. This study is the first one to demonstrate the presence of mannitol‐specific human IgE in a sensitized allergic subject to validate an IgE‐mediated hypersensitivity mechanism for mannitol.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15479277</pmid><doi>10.1111/j.1365-2222.2004.02079.x</doi><tpages>8</tpages></addata></record> |
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| ispartof | Clinical and experimental allergy, 2004-10, Vol.34 (10), p.1602-1609 |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult alditol-protein conjugates Allergens - immunology Allergic diseases anaphylaxis Anaphylaxis - blood Anaphylaxis - immunology Biological and medical sciences chemical allergy Chromatography, High Pressure Liquid - methods cisapride Cisapride - adverse effects Cisapride - immunology Enzyme-Linked Immunosorbent Assay - methods excipient Excipients - adverse effects Female food additive Food Additives - adverse effects Food Hypersensitivity - blood Food Hypersensitivity - immunology Fundamental and applied biological sciences. Psychology Fundamental immunology hapten Humans Immunoglobulin E - blood Immunoglobulin E - immunology Immunopathology mannitol Mannitol - adverse effects Mannitol - immunology mannitol-BSA mannitol-specific IgE Medical sciences Punicaceae - adverse effects Punicaceae - immunology Skin Tests - methods Sorbitol - immunology Sugar Alcohols - immunology |
| title | Anaphylaxis to excipient mannitol: evidence for an immunoglobulin E-mediated mechanism |
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