Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome
Abstract Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow...
Gespeichert in:
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.) Fla.), 2015-10, Vol.160 (2), p.237-243 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 243 |
|---|---|
| container_issue | 2 |
| container_start_page | 237 |
| container_title | Clinical immunology (Orlando, Fla.) |
| container_volume | 160 |
| creator | Volokhina, Elena B van de Kar, Nicole C.A.J Bergseth, Grethe van der Velden, Thea J.A.M Westra, Dineke Wetzels, Jack F.M van den Heuvel, Lambertus P Mollnes, Tom Eirik |
| description | Abstract Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1–2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p = 0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens. |
| doi_str_mv | 10.1016/j.clim.2015.05.018 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_crist</sourceid><recordid>TN_cdi_cristin_nora_10037_8996</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S1521661615002089</els_id><sourcerecordid>1751205906</sourcerecordid><originalsourceid>FETCH-LOGICAL-c511t-4ab3b6ab9ec3ee816f02f676ccf6a7a72d88a66b49f6fa542d34200e0cc97c3</originalsourceid><addsrcrecordid>eNqNkk1r1kAQx4MotrZ-AQ-yRw_mcWaTbBIQoRTfoODh6X3ZbCZ2Hze7cTcpxk_fDU-r4KEIAzOH37z-J8teIewQULw77LQ1444DVjtIhs2T7BQrjnkNRfX0PhYCxUn2IsYDAFSci-fZCReIWDb8NPu1JxfNbG7pLQtkjeosMeV6Riqu-URh8GGknlnV-aBmH1Y2emdSYNx35gdGerHm9zKqjs03FNS0MuOYmtfJaGXZDY3errPRbAk0JhdX1wc_0nn2bFA20st7f5btP328vvySX337_PXy4irXFeKcl6orOqG6lnRB1KAYgA-iFloPQtWq5n3TKCG6sh3EoKqS90XJAQi0bmtdnGWvj1V1MHE2Trq0hUSAopZN24oEvDkCU_A_F4qzHE3UZK1y5Jcosa6QQ9XC_6Ao2oLXHBLKH9r6GAMNcgpmVGFNreWmnTzITTu5aSchGTZ_Z52WLp38T8qDWAl4fwQo3evWUJBRG3KaehNIz7L35vH6H_5JT4jbVPpBK8WDX4JLSkiUkUuQ--17tufBCoBD0xZ37L3A3w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1716932720</pqid></control><display><type>article</type><title>Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome</title><source>MEDLINE</source><source>NORA - Norwegian Open Research Archives</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Volokhina, Elena B ; van de Kar, Nicole C.A.J ; Bergseth, Grethe ; van der Velden, Thea J.A.M ; Westra, Dineke ; Wetzels, Jack F.M ; van den Heuvel, Lambertus P ; Mollnes, Tom Eirik</creator><creatorcontrib>Volokhina, Elena B ; van de Kar, Nicole C.A.J ; Bergseth, Grethe ; van der Velden, Thea J.A.M ; Westra, Dineke ; Wetzels, Jack F.M ; van den Heuvel, Lambertus P ; Mollnes, Tom Eirik</creatorcontrib><description>Abstract Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1–2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p = 0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens.</description><identifier>ISSN: 1521-6616</identifier><identifier>ISSN: 1521-7035</identifier><identifier>EISSN: 1521-7035</identifier><identifier>DOI: 10.1016/j.clim.2015.05.018</identifier><identifier>PMID: 26111482</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Allergy and Immunology ; Antibodies, Monoclonal, Humanized - therapeutic use ; Atypical Hemolytic Uremic Syndrome - drug therapy ; Atypical Hemolytic Uremic Syndrome - immunology ; Child ; Child, Preschool ; Clinical medical disciplines: 750 ; Complement ; Complement Activation - immunology ; Complement Inactivating Agents - therapeutic use ; Dose-Response Relationship, Drug ; Drug Monitoring - instrumentation ; Drug Monitoring - methods ; Eculizumab ; Female ; Hemolytic uremic syndrome ; Humans ; Klinisk medisinske fag: 750 ; Male ; Medical disciplines: 700 ; Medisinske Fag: 700 ; Personalized therapy ; Reagent Kits, Diagnostic ; Reproducibility of Results ; VDP ; Young Adult</subject><ispartof>Clinical immunology (Orlando, Fla.), 2015-10, Vol.160 (2), p.237-243</ispartof><rights>The Authors</rights><rights>2015 The Authors</rights><rights>Copyright © 2015. Published by Elsevier Inc.</rights><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-4ab3b6ab9ec3ee816f02f676ccf6a7a72d88a66b49f6fa542d34200e0cc97c3</citedby><cites>FETCH-LOGICAL-c511t-4ab3b6ab9ec3ee816f02f676ccf6a7a72d88a66b49f6fa542d34200e0cc97c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2015.05.018$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3550,26567,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26111482$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Volokhina, Elena B</creatorcontrib><creatorcontrib>van de Kar, Nicole C.A.J</creatorcontrib><creatorcontrib>Bergseth, Grethe</creatorcontrib><creatorcontrib>van der Velden, Thea J.A.M</creatorcontrib><creatorcontrib>Westra, Dineke</creatorcontrib><creatorcontrib>Wetzels, Jack F.M</creatorcontrib><creatorcontrib>van den Heuvel, Lambertus P</creatorcontrib><creatorcontrib>Mollnes, Tom Eirik</creatorcontrib><title>Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome</title><title>Clinical immunology (Orlando, Fla.)</title><addtitle>Clin Immunol</addtitle><description>Abstract Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1–2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p = 0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Allergy and Immunology</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Atypical Hemolytic Uremic Syndrome - drug therapy</subject><subject>Atypical Hemolytic Uremic Syndrome - immunology</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Clinical medical disciplines: 750</subject><subject>Complement</subject><subject>Complement Activation - immunology</subject><subject>Complement Inactivating Agents - therapeutic use</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Monitoring - instrumentation</subject><subject>Drug Monitoring - methods</subject><subject>Eculizumab</subject><subject>Female</subject><subject>Hemolytic uremic syndrome</subject><subject>Humans</subject><subject>Klinisk medisinske fag: 750</subject><subject>Male</subject><subject>Medical disciplines: 700</subject><subject>Medisinske Fag: 700</subject><subject>Personalized therapy</subject><subject>Reagent Kits, Diagnostic</subject><subject>Reproducibility of Results</subject><subject>VDP</subject><subject>Young Adult</subject><issn>1521-6616</issn><issn>1521-7035</issn><issn>1521-7035</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNqNkk1r1kAQx4MotrZ-AQ-yRw_mcWaTbBIQoRTfoODh6X3ZbCZ2Hze7cTcpxk_fDU-r4KEIAzOH37z-J8teIewQULw77LQ1444DVjtIhs2T7BQrjnkNRfX0PhYCxUn2IsYDAFSci-fZCReIWDb8NPu1JxfNbG7pLQtkjeosMeV6Riqu-URh8GGknlnV-aBmH1Y2emdSYNx35gdGerHm9zKqjs03FNS0MuOYmtfJaGXZDY3errPRbAk0JhdX1wc_0nn2bFA20st7f5btP328vvySX337_PXy4irXFeKcl6orOqG6lnRB1KAYgA-iFloPQtWq5n3TKCG6sh3EoKqS90XJAQi0bmtdnGWvj1V1MHE2Trq0hUSAopZN24oEvDkCU_A_F4qzHE3UZK1y5Jcosa6QQ9XC_6Ao2oLXHBLKH9r6GAMNcgpmVGFNreWmnTzITTu5aSchGTZ_Z52WLp38T8qDWAl4fwQo3evWUJBRG3KaehNIz7L35vH6H_5JT4jbVPpBK8WDX4JLSkiUkUuQ--17tufBCoBD0xZ37L3A3w</recordid><startdate>20151001</startdate><enddate>20151001</enddate><creator>Volokhina, Elena B</creator><creator>van de Kar, Nicole C.A.J</creator><creator>Bergseth, Grethe</creator><creator>van der Velden, Thea J.A.M</creator><creator>Westra, Dineke</creator><creator>Wetzels, Jack F.M</creator><creator>van den Heuvel, Lambertus P</creator><creator>Mollnes, Tom Eirik</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>7T5</scope><scope>H94</scope><scope>3HK</scope></search><sort><creationdate>20151001</creationdate><title>Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome</title><author>Volokhina, Elena B ; van de Kar, Nicole C.A.J ; Bergseth, Grethe ; van der Velden, Thea J.A.M ; Westra, Dineke ; Wetzels, Jack F.M ; van den Heuvel, Lambertus P ; Mollnes, Tom Eirik</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-4ab3b6ab9ec3ee816f02f676ccf6a7a72d88a66b49f6fa542d34200e0cc97c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Allergy and Immunology</topic><topic>Antibodies, Monoclonal, Humanized - therapeutic use</topic><topic>Atypical Hemolytic Uremic Syndrome - drug therapy</topic><topic>Atypical Hemolytic Uremic Syndrome - immunology</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Clinical medical disciplines: 750</topic><topic>Complement</topic><topic>Complement Activation - immunology</topic><topic>Complement Inactivating Agents - therapeutic use</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Monitoring - instrumentation</topic><topic>Drug Monitoring - methods</topic><topic>Eculizumab</topic><topic>Female</topic><topic>Hemolytic uremic syndrome</topic><topic>Humans</topic><topic>Klinisk medisinske fag: 750</topic><topic>Male</topic><topic>Medical disciplines: 700</topic><topic>Medisinske Fag: 700</topic><topic>Personalized therapy</topic><topic>Reagent Kits, Diagnostic</topic><topic>Reproducibility of Results</topic><topic>VDP</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Volokhina, Elena B</creatorcontrib><creatorcontrib>van de Kar, Nicole C.A.J</creatorcontrib><creatorcontrib>Bergseth, Grethe</creatorcontrib><creatorcontrib>van der Velden, Thea J.A.M</creatorcontrib><creatorcontrib>Westra, Dineke</creatorcontrib><creatorcontrib>Wetzels, Jack F.M</creatorcontrib><creatorcontrib>van den Heuvel, Lambertus P</creatorcontrib><creatorcontrib>Mollnes, Tom Eirik</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>NORA - Norwegian Open Research Archives</collection><jtitle>Clinical immunology (Orlando, Fla.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Volokhina, Elena B</au><au>van de Kar, Nicole C.A.J</au><au>Bergseth, Grethe</au><au>van der Velden, Thea J.A.M</au><au>Westra, Dineke</au><au>Wetzels, Jack F.M</au><au>van den Heuvel, Lambertus P</au><au>Mollnes, Tom Eirik</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome</atitle><jtitle>Clinical immunology (Orlando, Fla.)</jtitle><addtitle>Clin Immunol</addtitle><date>2015-10-01</date><risdate>2015</risdate><volume>160</volume><issue>2</issue><spage>237</spage><epage>243</epage><pages>237-243</pages><issn>1521-6616</issn><issn>1521-7035</issn><eissn>1521-7035</eissn><abstract>Abstract Complement C5 inhibitor eculizumab treatment in atypical hemolytic uremic syndrome is effective, but associated with high costs. Complement inhibition monitoring in these patients has not been standardized. In this study we evaluated novel functional assays for application in routine follow-up. We documented that the Wieslab® complement screen assay showed a sensitivity of 1–2% of C5 activity by adding purified C5 or normal human serum to a C5 deficient serum. All the patient samples obtained during the treatment course, were completely blocked for terminal complement pathway activity for up to four weeks after the eculizumab infusion. Levels of complexes between eculizumab and C5 were inversely correlated to the complement activity (p = 0.01). Moreover, titrating serum from eculizumab-treated patients into normal serum revealed that eculizumab was present in excess up to four weeks after infusion. Thus, we demonstrate sensitive, reliable and easy-performed assays which can be used to design individual eculizumab dosage regimens.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26111482</pmid><doi>10.1016/j.clim.2015.05.018</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1521-6616 |
| ispartof | Clinical immunology (Orlando, Fla.), 2015-10, Vol.160 (2), p.237-243 |
| issn | 1521-6616 1521-7035 1521-7035 |
| language | eng |
| recordid | cdi_cristin_nora_10037_8996 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; Elsevier ScienceDirect Journals Complete |
| subjects | Adolescent Adult Allergy and Immunology Antibodies, Monoclonal, Humanized - therapeutic use Atypical Hemolytic Uremic Syndrome - drug therapy Atypical Hemolytic Uremic Syndrome - immunology Child Child, Preschool Clinical medical disciplines: 750 Complement Complement Activation - immunology Complement Inactivating Agents - therapeutic use Dose-Response Relationship, Drug Drug Monitoring - instrumentation Drug Monitoring - methods Eculizumab Female Hemolytic uremic syndrome Humans Klinisk medisinske fag: 750 Male Medical disciplines: 700 Medisinske Fag: 700 Personalized therapy Reagent Kits, Diagnostic Reproducibility of Results VDP Young Adult |
| title | Sensitive, reliable and easy-performed laboratory monitoring of eculizumab therapy in atypical hemolytic uremic syndrome |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T11%3A51%3A29IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_crist&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Sensitive,%20reliable%20and%20easy-performed%20laboratory%20monitoring%20of%20eculizumab%20therapy%20in%20atypical%20hemolytic%20uremic%20syndrome&rft.jtitle=Clinical%20immunology%20(Orlando,%20Fla.)&rft.au=Volokhina,%20Elena%20B&rft.date=2015-10-01&rft.volume=160&rft.issue=2&rft.spage=237&rft.epage=243&rft.pages=237-243&rft.issn=1521-6616&rft.eissn=1521-7035&rft_id=info:doi/10.1016/j.clim.2015.05.018&rft_dat=%3Cproquest_crist%3E1751205906%3C/proquest_crist%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1716932720&rft_id=info:pmid/26111482&rft_els_id=1_s2_0_S1521661615002089&rfr_iscdi=true |