The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice

Summary Background Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut alle...

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Veröffentlicht in:Clinical and experimental allergy 2012-02, Vol.42 (2), p.326-336
Hauptverfasser: Kulis, M., Chen, X., Lew, J., Wang, Q., Patel, O. P., Zhuang, Y., Murray, K. S., Duncan, M. W., Porterfield, H. S., W. Burks, A., Dreskin, S. C.
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container_issue 2
container_start_page 326
container_title Clinical and experimental allergy
container_volume 42
creator Kulis, M.
Chen, X.
Lew, J.
Wang, Q.
Patel, O. P.
Zhuang, Y.
Murray, K. S.
Duncan, M. W.
Porterfield, H. S.
W. Burks, A.
Dreskin, S. C.
description Summary Background Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut allergic sera. Objectives To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. Methods An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. Results Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P 
doi_str_mv 10.1111/j.1365-2222.2011.03934.x
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P. ; Zhuang, Y. ; Murray, K. S. ; Duncan, M. W. ; Porterfield, H. S. ; W. Burks, A. ; Dreskin, S. C.</creator><creatorcontrib>Kulis, M. ; Chen, X. ; Lew, J. ; Wang, Q. ; Patel, O. P. ; Zhuang, Y. ; Murray, K. S. ; Duncan, M. W. ; Porterfield, H. S. ; W. Burks, A. ; Dreskin, S. C.</creatorcontrib><description>Summary Background Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut allergic sera. Objectives To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. Methods An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. Results Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P &lt; 0.05) and a smaller decrease in body temperature (P &lt; 0.01). Results with the basophil histamine release assay corroborated these findings (P &lt; 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut‐allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP‐1) release compared with placebo (P &lt; 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges. Conclusions and Clinical Relevance Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut‐allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.</description><identifier>ISSN: 0954-7894</identifier><identifier>EISSN: 1365-2222</identifier><identifier>DOI: 10.1111/j.1365-2222.2011.03934.x</identifier><identifier>PMID: 22288514</identifier><language>eng</language><publisher>Oxford: Blackwell Publishing Ltd</publisher><subject>2S Albumins, Plant - immunology ; 2S Albumins, Plant - pharmacology ; Albumin ; Allergens ; Allergic diseases ; Anaphylaxis ; Anaphylaxis - immunology ; Anaphylaxis - therapy ; Animal models ; Animals ; Antigens, Plant - immunology ; Antigens, Plant - pharmacology ; Ara h 2 ; Ara h 2 antigen ; Ara h 6 ; Arachis - adverse effects ; Arachis - immunology ; Arachis hypogaea ; Basophils - immunology ; Biological and medical sciences ; Blood ; Body temperature ; Chromatography ; desensitization ; Desensitization, Immunologic ; Digestive allergic diseases ; Disease Models, Animal ; Female ; Filtration ; food allergy ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Glycoproteins - immunology ; Glycoproteins - pharmacology ; Histamine ; Histamine - immunology ; human basophil assay ; Humans ; Hypersensitivity ; Immunoglobulin E ; Immunopathology ; Immunotherapy ; Leukocytes (basophilic) ; Male ; Mast cells ; Medical sciences ; Mice ; mouse model ; Nuts ; peanut allergy ; Peanut Hypersensitivity - immunology ; Peanut Hypersensitivity - therapy ; Proteinase ; Provocation tests ; Tryptases - immunology</subject><ispartof>Clinical and experimental allergy, 2012-02, Vol.42 (2), p.326-336</ispartof><rights>2011 Blackwell Publishing Ltd</rights><rights>2015 INIST-CNRS</rights><rights>2011 Blackwell Publishing Ltd.</rights><rights>Copyright © 2012 Blackwell Publishing Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6014-614abd3d2536c3927f51c1508cf130479dbecc45202fd2ca8e322d00573b58df3</citedby><cites>FETCH-LOGICAL-c6014-614abd3d2536c3927f51c1508cf130479dbecc45202fd2ca8e322d00573b58df3</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.1365-2222.2011.03934.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2222.2011.03934.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25433502$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22288514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kulis, M.</creatorcontrib><creatorcontrib>Chen, X.</creatorcontrib><creatorcontrib>Lew, J.</creatorcontrib><creatorcontrib>Wang, Q.</creatorcontrib><creatorcontrib>Patel, O. P.</creatorcontrib><creatorcontrib>Zhuang, Y.</creatorcontrib><creatorcontrib>Murray, K. S.</creatorcontrib><creatorcontrib>Duncan, M. W.</creatorcontrib><creatorcontrib>Porterfield, H. S.</creatorcontrib><creatorcontrib>W. Burks, A.</creatorcontrib><creatorcontrib>Dreskin, S. C.</creatorcontrib><title>The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice</title><title>Clinical and experimental allergy</title><addtitle>Clin Exp Allergy</addtitle><description>Summary Background Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut allergic sera. Objectives To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. Methods An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. Results Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P &lt; 0.05) and a smaller decrease in body temperature (P &lt; 0.01). Results with the basophil histamine release assay corroborated these findings (P &lt; 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut‐allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP‐1) release compared with placebo (P &lt; 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges. Conclusions and Clinical Relevance Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut‐allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.</description><subject>2S Albumins, Plant - immunology</subject><subject>2S Albumins, Plant - pharmacology</subject><subject>Albumin</subject><subject>Allergens</subject><subject>Allergic diseases</subject><subject>Anaphylaxis</subject><subject>Anaphylaxis - immunology</subject><subject>Anaphylaxis - therapy</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antigens, Plant - immunology</subject><subject>Antigens, Plant - pharmacology</subject><subject>Ara h 2</subject><subject>Ara h 2 antigen</subject><subject>Ara h 6</subject><subject>Arachis - adverse effects</subject><subject>Arachis - immunology</subject><subject>Arachis hypogaea</subject><subject>Basophils - immunology</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Body temperature</subject><subject>Chromatography</subject><subject>desensitization</subject><subject>Desensitization, Immunologic</subject><subject>Digestive allergic diseases</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Filtration</subject><subject>food allergy</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Glycoproteins - immunology</subject><subject>Glycoproteins - pharmacology</subject><subject>Histamine</subject><subject>Histamine - immunology</subject><subject>human basophil assay</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Immunoglobulin E</subject><subject>Immunopathology</subject><subject>Immunotherapy</subject><subject>Leukocytes (basophilic)</subject><subject>Male</subject><subject>Mast cells</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>mouse model</subject><subject>Nuts</subject><subject>peanut allergy</subject><subject>Peanut Hypersensitivity - immunology</subject><subject>Peanut Hypersensitivity - therapy</subject><subject>Proteinase</subject><subject>Provocation tests</subject><subject>Tryptases - immunology</subject><issn>0954-7894</issn><issn>1365-2222</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNktuO0zAQhiMEYsvCKyBLCHGzKT7EOVywUlXtLkjVgmARl9bUmTQuTlLsZGl5GJ4VZ1vK4QZ8M5bn-3-PrT-KCKNTFtbL9ZSJVMY8rCmnjE2pKEQy3d6LJsfG_WhCC5nEWV4kJ9Ej79eUUiGL_GF0Etp5Llkyib7f1Ej4BwJ2OTSmDdWiW2HrSVeRmQNdG0_q3aZbAcLZeEJqwgm05WGfnhFwSPpg08C6cwSt0abv3J0DtLCpdxa2wWXUaGgJVhXq3tyi3ZESfbjL9OYbkg1CO_TxfgKjSWM0Po4eVGA9PjnU0-jj5cXN_HW8eHv1Zj5bxDqlLIlTlsCyFCWXItWi4FklmWaS5rpigiZZUS5R60RyyquSa8hRcF5SKjOxlHlZidPofO-7GZYNlhrb3oFVG2cacDvVgVF_dlpTq1V3qwTPqBBpMHhxMHDdlwF9rxrjNVoLLXaDVwUXrEgzlvybZAXnaSJH8tlf5LobXBv-QTGZyKxIKc0Dle8p7TrvHVbHqRlVY1rUWo2hUGMo1JgWdZcWtQ3Sp7-_-ij8GY8APD8A4DXYykGrjf_FhSGFpDxwr_bcV2Nx998DqPnFbNwFfbzXG9_j9qgH91mlmcik-nR9pd5fz_PF5Zyqd-IHIhjp3A</recordid><startdate>201202</startdate><enddate>201202</enddate><creator>Kulis, M.</creator><creator>Chen, X.</creator><creator>Lew, J.</creator><creator>Wang, Q.</creator><creator>Patel, O. P.</creator><creator>Zhuang, Y.</creator><creator>Murray, K. S.</creator><creator>Duncan, M. W.</creator><creator>Porterfield, H. S.</creator><creator>W. Burks, A.</creator><creator>Dreskin, S. C.</creator><general>Blackwell Publishing 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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201202</creationdate><title>The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice</title><author>Kulis, M. ; Chen, X. ; Lew, J. ; Wang, Q. ; Patel, O. P. ; Zhuang, Y. ; Murray, K. S. ; Duncan, M. W. ; Porterfield, H. S. ; W. Burks, A. ; Dreskin, S. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6014-614abd3d2536c3927f51c1508cf130479dbecc45202fd2ca8e322d00573b58df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>2S Albumins, Plant - immunology</topic><topic>2S Albumins, Plant - pharmacology</topic><topic>Albumin</topic><topic>Allergens</topic><topic>Allergic diseases</topic><topic>Anaphylaxis</topic><topic>Anaphylaxis - immunology</topic><topic>Anaphylaxis - therapy</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antigens, Plant - immunology</topic><topic>Antigens, Plant - pharmacology</topic><topic>Ara h 2</topic><topic>Ara h 2 antigen</topic><topic>Ara h 6</topic><topic>Arachis - adverse effects</topic><topic>Arachis - immunology</topic><topic>Arachis hypogaea</topic><topic>Basophils - immunology</topic><topic>Biological and medical sciences</topic><topic>Blood</topic><topic>Body temperature</topic><topic>Chromatography</topic><topic>desensitization</topic><topic>Desensitization, Immunologic</topic><topic>Digestive allergic diseases</topic><topic>Disease Models, Animal</topic><topic>Female</topic><topic>Filtration</topic><topic>food allergy</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Glycoproteins - immunology</topic><topic>Glycoproteins - pharmacology</topic><topic>Histamine</topic><topic>Histamine - immunology</topic><topic>human basophil assay</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Immunoglobulin E</topic><topic>Immunopathology</topic><topic>Immunotherapy</topic><topic>Leukocytes (basophilic)</topic><topic>Male</topic><topic>Mast cells</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>mouse model</topic><topic>Nuts</topic><topic>peanut allergy</topic><topic>Peanut Hypersensitivity - immunology</topic><topic>Peanut Hypersensitivity - therapy</topic><topic>Proteinase</topic><topic>Provocation tests</topic><topic>Tryptases - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kulis, M.</creatorcontrib><creatorcontrib>Chen, X.</creatorcontrib><creatorcontrib>Lew, J.</creatorcontrib><creatorcontrib>Wang, Q.</creatorcontrib><creatorcontrib>Patel, O. P.</creatorcontrib><creatorcontrib>Zhuang, Y.</creatorcontrib><creatorcontrib>Murray, K. S.</creatorcontrib><creatorcontrib>Duncan, M. W.</creatorcontrib><creatorcontrib>Porterfield, H. S.</creatorcontrib><creatorcontrib>W. Burks, A.</creatorcontrib><creatorcontrib>Dreskin, S. C.</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 &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical and experimental allergy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kulis, M.</au><au>Chen, X.</au><au>Lew, J.</au><au>Wang, Q.</au><au>Patel, O. P.</au><au>Zhuang, Y.</au><au>Murray, K. S.</au><au>Duncan, M. W.</au><au>Porterfield, H. S.</au><au>W. Burks, A.</au><au>Dreskin, S. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice</atitle><jtitle>Clinical and experimental allergy</jtitle><addtitle>Clin Exp Allergy</addtitle><date>2012-02</date><risdate>2012</risdate><volume>42</volume><issue>2</issue><spage>326</spage><epage>336</epage><pages>326-336</pages><issn>0954-7894</issn><eissn>1365-2222</eissn><abstract>Summary Background Ara h 2 and Ara h 6, co‐purified together in a 13–25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX‐38 cells sensitized with IgE from human peanut allergic sera. Objectives To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. Methods An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. Results Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P &lt; 0.05) and a smaller decrease in body temperature (P &lt; 0.01). Results with the basophil histamine release assay corroborated these findings (P &lt; 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut‐allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP‐1) release compared with placebo (P &lt; 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges. Conclusions and Clinical Relevance Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut‐allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.</abstract><cop>Oxford</cop><pub>Blackwell Publishing Ltd</pub><pmid>22288514</pmid><doi>10.1111/j.1365-2222.2011.03934.x</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects 2S Albumins, Plant - immunology
2S Albumins, Plant - pharmacology
Albumin
Allergens
Allergic diseases
Anaphylaxis
Anaphylaxis - immunology
Anaphylaxis - therapy
Animal models
Animals
Antigens, Plant - immunology
Antigens, Plant - pharmacology
Ara h 2
Ara h 2 antigen
Ara h 6
Arachis - adverse effects
Arachis - immunology
Arachis hypogaea
Basophils - immunology
Biological and medical sciences
Blood
Body temperature
Chromatography
desensitization
Desensitization, Immunologic
Digestive allergic diseases
Disease Models, Animal
Female
Filtration
food allergy
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Glycoproteins - immunology
Glycoproteins - pharmacology
Histamine
Histamine - immunology
human basophil assay
Humans
Hypersensitivity
Immunoglobulin E
Immunopathology
Immunotherapy
Leukocytes (basophilic)
Male
Mast cells
Medical sciences
Mice
mouse model
Nuts
peanut allergy
Peanut Hypersensitivity - immunology
Peanut Hypersensitivity - therapy
Proteinase
Provocation tests
Tryptases - immunology
title The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice
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