Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity

Background Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patien...

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Veröffentlicht in:Allergy (Copenhagen) 2020-10, Vol.75 (10), p.2562-2573
Hauptverfasser: Ariza, Adriana, Fernández‐Santamaría, Rubén, Meng, Xiaoli, Salas, María, Ogese, Monday O., Tailor, Arun, Bogas, Gádor, Torres, María José, Naisbitt, Dean J.
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container_end_page 2573
container_issue 10
container_start_page 2562
container_title Allergy (Copenhagen)
container_volume 75
creator Ariza, Adriana
Fernández‐Santamaría, Rubén
Meng, Xiaoli
Salas, María
Ogese, Monday O.
Tailor, Arun
Bogas, Gádor
Torres, María José
Naisbitt, Dean J.
description Background Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patients with immediate hypersensitivity to AX‐Clav, to assess whether these T‐cells display the same specificity as that detected in skin and provocation testing, and to explore T‐cell activation pathways. Methods Drug‐specific T‐cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4+/CD8+ phenotype and chemokine receptor expression were analyzed by flow cytometry. Results 110 AX‐specific and 96 Clav‐specific T‐cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX‐ and Clav‐specific clones was dose‐dependent, and no cross‐reactivity was observed. AX‐ and Clav‐specific clones required antigen‐presenting cells to proliferate, and drugs were presented to CD4+ and CD8+ T‐cells by MHC class‐II and I, respectively. A higher secretion of IL‐13 and IL‐5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10. Conclusions Our study details the antigen specificity and phenotype of T‐cell clones generated from patients with AX‐Clav‐induced immediate hypersensitivity diagnosed by positive skin test. AX‐ and Clav‐specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed. AX‐ and Clav‐specific T‐cell clones can be generated from the same patient with immediate hypersensitivity, irrespective of whether AX or Clav is the culprit drug in the combination AX‐Clav. No cross‐reactivity between AX and Clav is detected. Differences in cytokine secretion are observed between T‐cell clones generated against the culprit or the alternative drug in the combination AX‐Clav.Abbreviations: AX, amoxicillin; Clav, clavulanic acid.
doi_str_mv 10.1111/all.14298
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Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patients with immediate hypersensitivity to AX‐Clav, to assess whether these T‐cells display the same specificity as that detected in skin and provocation testing, and to explore T‐cell activation pathways. Methods Drug‐specific T‐cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4+/CD8+ phenotype and chemokine receptor expression were analyzed by flow cytometry. Results 110 AX‐specific and 96 Clav‐specific T‐cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX‐ and Clav‐specific clones was dose‐dependent, and no cross‐reactivity was observed. AX‐ and Clav‐specific clones required antigen‐presenting cells to proliferate, and drugs were presented to CD4+ and CD8+ T‐cells by MHC class‐II and I, respectively. A higher secretion of IL‐13 and IL‐5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10. Conclusions Our study details the antigen specificity and phenotype of T‐cell clones generated from patients with AX‐Clav‐induced immediate hypersensitivity diagnosed by positive skin test. AX‐ and Clav‐specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed. AX‐ and Clav‐specific T‐cell clones can be generated from the same patient with immediate hypersensitivity, irrespective of whether AX or Clav is the culprit drug in the combination AX‐Clav. No cross‐reactivity between AX and Clav is detected. Differences in cytokine secretion are observed between T‐cell clones generated against the culprit or the alternative drug in the combination AX‐Clav.Abbreviations: AX, amoxicillin; Clav, clavulanic acid.</description><identifier>ISSN: 0105-4538</identifier><identifier>EISSN: 1398-9995</identifier><identifier>DOI: 10.1111/all.14298</identifier><identifier>PMID: 32246774</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject>Allergies ; Allergy ; Amoxicillin ; Amoxicillin - adverse effects ; Antibiotics ; Antigen-presenting cells ; Antigens ; CD4 antigen ; CD69 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cell activation ; Chemokines ; Clavulanic acid ; Clavulanic Acid - adverse effects ; Clone Cells ; CXCR3 protein ; Cytokines ; Drug Hypersensitivity - diagnosis ; Flow cytometry ; Humans ; Hypersensitivity (immediate) ; Hypersensitivity, Immediate - diagnosis ; immediate hypersensitivity ; Immunology ; Life Sciences &amp; Biomedicine ; Penicillin ; phenotype ; Phenotypes ; Science &amp; Technology ; Side effects ; Skin tests ; T-cell</subject><ispartof>Allergy (Copenhagen), 2020-10, Vol.75 (10), p.2562-2573</ispartof><rights>2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.</rights><rights>2020 EAACI and John Wiley and Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>10</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000535613600001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c3538-4d94f3c7265d6c2d3ca5e7c6a02b1a47311d6319ff262f48522cf8afdc4e41d83</citedby><cites>FETCH-LOGICAL-c3538-4d94f3c7265d6c2d3ca5e7c6a02b1a47311d6319ff262f48522cf8afdc4e41d83</cites><orcidid>0000-0002-0255-4280 ; 0000-0003-1524-9602 ; 0000-0001-5228-471X ; 0000-0002-0583-9492 ; 0000-0002-9698-3480 ; 0000-0003-4107-7832</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fall.14298$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fall.14298$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,1434,27929,27930,28253,45579,45580,46414,46838</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32246774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ariza, Adriana</creatorcontrib><creatorcontrib>Fernández‐Santamaría, Rubén</creatorcontrib><creatorcontrib>Meng, Xiaoli</creatorcontrib><creatorcontrib>Salas, María</creatorcontrib><creatorcontrib>Ogese, Monday O.</creatorcontrib><creatorcontrib>Tailor, Arun</creatorcontrib><creatorcontrib>Bogas, Gádor</creatorcontrib><creatorcontrib>Torres, María José</creatorcontrib><creatorcontrib>Naisbitt, Dean J.</creatorcontrib><title>Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity</title><title>Allergy (Copenhagen)</title><addtitle>ALLERGY</addtitle><addtitle>Allergy</addtitle><description>Background Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patients with immediate hypersensitivity to AX‐Clav, to assess whether these T‐cells display the same specificity as that detected in skin and provocation testing, and to explore T‐cell activation pathways. Methods Drug‐specific T‐cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4+/CD8+ phenotype and chemokine receptor expression were analyzed by flow cytometry. Results 110 AX‐specific and 96 Clav‐specific T‐cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX‐ and Clav‐specific clones was dose‐dependent, and no cross‐reactivity was observed. AX‐ and Clav‐specific clones required antigen‐presenting cells to proliferate, and drugs were presented to CD4+ and CD8+ T‐cells by MHC class‐II and I, respectively. A higher secretion of IL‐13 and IL‐5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10. Conclusions Our study details the antigen specificity and phenotype of T‐cell clones generated from patients with AX‐Clav‐induced immediate hypersensitivity diagnosed by positive skin test. AX‐ and Clav‐specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed. AX‐ and Clav‐specific T‐cell clones can be generated from the same patient with immediate hypersensitivity, irrespective of whether AX or Clav is the culprit drug in the combination AX‐Clav. No cross‐reactivity between AX and Clav is detected. Differences in cytokine secretion are observed between T‐cell clones generated against the culprit or the alternative drug in the combination AX‐Clav.Abbreviations: AX, amoxicillin; Clav, clavulanic acid.</description><subject>Allergies</subject><subject>Allergy</subject><subject>Amoxicillin</subject><subject>Amoxicillin - adverse effects</subject><subject>Antibiotics</subject><subject>Antigen-presenting cells</subject><subject>Antigens</subject><subject>CD4 antigen</subject><subject>CD69 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cell activation</subject><subject>Chemokines</subject><subject>Clavulanic acid</subject><subject>Clavulanic Acid - adverse effects</subject><subject>Clone Cells</subject><subject>CXCR3 protein</subject><subject>Cytokines</subject><subject>Drug Hypersensitivity - diagnosis</subject><subject>Flow cytometry</subject><subject>Humans</subject><subject>Hypersensitivity (immediate)</subject><subject>Hypersensitivity, Immediate - diagnosis</subject><subject>immediate hypersensitivity</subject><subject>Immunology</subject><subject>Life Sciences &amp; Biomedicine</subject><subject>Penicillin</subject><subject>phenotype</subject><subject>Phenotypes</subject><subject>Science &amp; Technology</subject><subject>Side effects</subject><subject>Skin tests</subject><subject>T-cell</subject><issn>0105-4538</issn><issn>1398-9995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><recordid>eNqNkctu1DAUhi1ERYfCghdAllghlNbXJF5WETdppG7KOvL4wrhy7GA7LcOmfQSekSfBdKbdIdWbY0vf-f2f_wDwBqNTXM-Z9P4UMyL6Z2CFqegbIQR_DlYII94wTvtj8DLnK4RQRwR6AY4pIaztOrYCt8NWJqmKSe6XLC4GGC2UU_zplPPeBSiDhsrL68XL4BSUymmYZ6Ocra_LP3e_lfG-EjGYDG2KE5yrjgklwxtXttBNk9FOFgN1Wr7D7W42KZuQXXHXruxegSMrfTavD_UEfPv08XL40qwvPn8dzteNotV_w7RglqqOtFy3imiqJDedaiUiGyxZRzHWLcXCWtISy3pOiLK9tFoxw7Du6Ql4t9edU_yxmFzGq7ikUL8cCeOMEiqYqNT7PaVSzDkZO87JTTLtRozGf1GPNerxPurKvj0oLps64iP5kG0FPuyBG7OJNqsaijKPWF0Gp7zFtK03hCvdP50eXLlf1hCXUGrr2aHVebP7v-XxfL3ee_8LyAKsTQ</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Ariza, Adriana</creator><creator>Fernández‐Santamaría, Rubén</creator><creator>Meng, Xiaoli</creator><creator>Salas, María</creator><creator>Ogese, Monday O.</creator><creator>Tailor, Arun</creator><creator>Bogas, Gádor</creator><creator>Torres, María José</creator><creator>Naisbitt, Dean J.</creator><general>Wiley</general><general>Blackwell Publishing Ltd</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</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><orcidid>https://orcid.org/0000-0002-0255-4280</orcidid><orcidid>https://orcid.org/0000-0003-1524-9602</orcidid><orcidid>https://orcid.org/0000-0001-5228-471X</orcidid><orcidid>https://orcid.org/0000-0002-0583-9492</orcidid><orcidid>https://orcid.org/0000-0002-9698-3480</orcidid><orcidid>https://orcid.org/0000-0003-4107-7832</orcidid></search><sort><creationdate>202010</creationdate><title>Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity</title><author>Ariza, Adriana ; Fernández‐Santamaría, Rubén ; Meng, Xiaoli ; Salas, María ; Ogese, Monday O. ; Tailor, Arun ; Bogas, Gádor ; Torres, María José ; Naisbitt, Dean J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-4d94f3c7265d6c2d3ca5e7c6a02b1a47311d6319ff262f48522cf8afdc4e41d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Allergies</topic><topic>Allergy</topic><topic>Amoxicillin</topic><topic>Amoxicillin - adverse effects</topic><topic>Antibiotics</topic><topic>Antigen-presenting cells</topic><topic>Antigens</topic><topic>CD4 antigen</topic><topic>CD69 antigen</topic><topic>CD8 antigen</topic><topic>CD8-Positive T-Lymphocytes</topic><topic>Cell activation</topic><topic>Chemokines</topic><topic>Clavulanic acid</topic><topic>Clavulanic Acid - adverse effects</topic><topic>Clone Cells</topic><topic>CXCR3 protein</topic><topic>Cytokines</topic><topic>Drug Hypersensitivity - diagnosis</topic><topic>Flow cytometry</topic><topic>Humans</topic><topic>Hypersensitivity (immediate)</topic><topic>Hypersensitivity, Immediate - diagnosis</topic><topic>immediate hypersensitivity</topic><topic>Immunology</topic><topic>Life Sciences &amp; Biomedicine</topic><topic>Penicillin</topic><topic>phenotype</topic><topic>Phenotypes</topic><topic>Science &amp; Technology</topic><topic>Side effects</topic><topic>Skin tests</topic><topic>T-cell</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ariza, Adriana</creatorcontrib><creatorcontrib>Fernández‐Santamaría, Rubén</creatorcontrib><creatorcontrib>Meng, Xiaoli</creatorcontrib><creatorcontrib>Salas, María</creatorcontrib><creatorcontrib>Ogese, Monday O.</creatorcontrib><creatorcontrib>Tailor, Arun</creatorcontrib><creatorcontrib>Bogas, Gádor</creatorcontrib><creatorcontrib>Torres, María José</creatorcontrib><creatorcontrib>Naisbitt, Dean J.</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</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><jtitle>Allergy (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ariza, Adriana</au><au>Fernández‐Santamaría, Rubén</au><au>Meng, Xiaoli</au><au>Salas, María</au><au>Ogese, Monday O.</au><au>Tailor, Arun</au><au>Bogas, Gádor</au><au>Torres, María José</au><au>Naisbitt, Dean J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity</atitle><jtitle>Allergy (Copenhagen)</jtitle><stitle>ALLERGY</stitle><addtitle>Allergy</addtitle><date>2020-10</date><risdate>2020</risdate><volume>75</volume><issue>10</issue><spage>2562</spage><epage>2573</epage><pages>2562-2573</pages><issn>0105-4538</issn><eissn>1398-9995</eissn><abstract>Background Betalactam (BL) antibiotics are the most common cause of drug hypersensitivity. Amoxicillin (AX), which is often prescribed alongside clavulanic acid (Clav), is the most common elicitor. The aim of this study was to determine whether AX and Clav‐responsive T‐cells are detectable in patients with immediate hypersensitivity to AX‐Clav, to assess whether these T‐cells display the same specificity as that detected in skin and provocation testing, and to explore T‐cell activation pathways. Methods Drug‐specific T‐cell clones were generated from immediate hypersensitive patients´ blood by serial dilution and repetitive mitogen stimulation. Antigen specificity was assessed by measurement of proliferation and cytokine release. CD4+/CD8+ phenotype and chemokine receptor expression were analyzed by flow cytometry. Results 110 AX‐specific and 96 Clav‐specific T‐cell clones were generated from seven patients with positive skin test to either AX or Clav. Proliferation of AX‐ and Clav‐specific clones was dose‐dependent, and no cross‐reactivity was observed. AX‐ and Clav‐specific clones required antigen‐presenting cells to proliferate, and drugs were presented to CD4+ and CD8+ T‐cells by MHC class‐II and I, respectively. A higher secretion of IL‐13 and IL‐5 was detected in presence of the culprit drug compared with the alternative drug. Clones expressed CD69, CCR4, CXCR3, and CCR10. Conclusions Our study details the antigen specificity and phenotype of T‐cell clones generated from patients with AX‐Clav‐induced immediate hypersensitivity diagnosed by positive skin test. AX‐ and Clav‐specific clones were generated from patients irrespective of whether AX or Clav was the culprit, although differences in cytokine secretion were observed. AX‐ and Clav‐specific T‐cell clones can be generated from the same patient with immediate hypersensitivity, irrespective of whether AX or Clav is the culprit drug in the combination AX‐Clav. No cross‐reactivity between AX and Clav is detected. Differences in cytokine secretion are observed between T‐cell clones generated against the culprit or the alternative drug in the combination AX‐Clav.Abbreviations: AX, amoxicillin; Clav, clavulanic acid.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>32246774</pmid><doi>10.1111/all.14298</doi><orcidid>https://orcid.org/0000-0002-0255-4280</orcidid><orcidid>https://orcid.org/0000-0003-1524-9602</orcidid><orcidid>https://orcid.org/0000-0001-5228-471X</orcidid><orcidid>https://orcid.org/0000-0002-0583-9492</orcidid><orcidid>https://orcid.org/0000-0002-9698-3480</orcidid><orcidid>https://orcid.org/0000-0003-4107-7832</orcidid></addata></record>
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subjects Allergies
Allergy
Amoxicillin
Amoxicillin - adverse effects
Antibiotics
Antigen-presenting cells
Antigens
CD4 antigen
CD69 antigen
CD8 antigen
CD8-Positive T-Lymphocytes
Cell activation
Chemokines
Clavulanic acid
Clavulanic Acid - adverse effects
Clone Cells
CXCR3 protein
Cytokines
Drug Hypersensitivity - diagnosis
Flow cytometry
Humans
Hypersensitivity (immediate)
Hypersensitivity, Immediate - diagnosis
immediate hypersensitivity
Immunology
Life Sciences & Biomedicine
Penicillin
phenotype
Phenotypes
Science & Technology
Side effects
Skin tests
T-cell
title Characterization of amoxicillin and clavulanic acid specific T‐cell clones from patients with immediate drug hypersensitivity
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