Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation
Abstract Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the pr...
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| Veröffentlicht in: | Human immunology 2015-08, Vol.76 (8), p.546-552 |
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| creator | Higgins, Rob Lowe, David Daga, Sunil Hathaway, Mark Williams, C Lam, F.T Kashi, Habib Tan, Lam Chin Imray, Chris Fletcher, Simon Krishnan, Nithya Hart, Pat Zehnder, Daniel Briggs, David |
| description | Abstract Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30 days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) ( p < 0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI 1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others ( p < 0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels. |
| doi_str_mv | 10.1016/j.humimm.2015.06.013 |
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DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30 days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) ( p < 0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others ( p < 0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.</description><identifier>ISSN: 0198-8859</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2015.06.013</identifier><identifier>PMID: 26116896</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; Aged ; Allergy and Immunology ; Antibody Formation - immunology ; Antibody incompatible kidney transplantation ; Antibody mediated rejection ; Antibody Specificity - immunology ; Female ; Graft Rejection - immunology ; Graft Rejection - therapy ; HLA antibodies ; HLA Antigens - immunology ; HLA Class 1 ; HLA Class 2 ; Humans ; Immunosuppressive Agents - therapeutic use ; Isoantibodies - blood ; Isoantibodies - immunology ; Kidney Transplantation - adverse effects ; Male ; Middle Aged ; Patient Outcome Assessment ; Plasmapheresis - methods ; Pregnancy ; Time Factors ; Transfusion ; Young Adult</subject><ispartof>Human immunology, 2015-08, Vol.76 (8), p.546-552</ispartof><rights>2015</rights><rights>Copyright © 2015. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-f459f0ca086e649113f4049a6e152c0d1f51151606890ce6e21a66c5444284fc3</citedby><cites>FETCH-LOGICAL-c450t-f459f0ca086e649113f4049a6e152c0d1f51151606890ce6e21a66c5444284fc3</cites><orcidid>0000-0002-4592-8561</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.humimm.2015.06.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26116896$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Higgins, Rob</creatorcontrib><creatorcontrib>Lowe, David</creatorcontrib><creatorcontrib>Daga, Sunil</creatorcontrib><creatorcontrib>Hathaway, Mark</creatorcontrib><creatorcontrib>Williams, C</creatorcontrib><creatorcontrib>Lam, F.T</creatorcontrib><creatorcontrib>Kashi, Habib</creatorcontrib><creatorcontrib>Tan, Lam Chin</creatorcontrib><creatorcontrib>Imray, Chris</creatorcontrib><creatorcontrib>Fletcher, Simon</creatorcontrib><creatorcontrib>Krishnan, Nithya</creatorcontrib><creatorcontrib>Hart, Pat</creatorcontrib><creatorcontrib>Zehnder, Daniel</creatorcontrib><creatorcontrib>Briggs, David</creatorcontrib><title>Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation</title><title>Human immunology</title><addtitle>Hum Immunol</addtitle><description>Abstract Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30 days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) ( p < 0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others ( p < 0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.</description><subject>Adult</subject><subject>Aged</subject><subject>Allergy and Immunology</subject><subject>Antibody Formation - immunology</subject><subject>Antibody incompatible kidney transplantation</subject><subject>Antibody mediated rejection</subject><subject>Antibody Specificity - immunology</subject><subject>Female</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - therapy</subject><subject>HLA antibodies</subject><subject>HLA Antigens - immunology</subject><subject>HLA Class 1</subject><subject>HLA Class 2</subject><subject>Humans</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Isoantibodies - blood</subject><subject>Isoantibodies - immunology</subject><subject>Kidney Transplantation - adverse effects</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Patient Outcome Assessment</subject><subject>Plasmapheresis - methods</subject><subject>Pregnancy</subject><subject>Time Factors</subject><subject>Transfusion</subject><subject>Young Adult</subject><issn>0198-8859</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUsFu1DAUtBCILoU_QChHLgnvZW0nviBVVaFIK4EEnC2v89J6SezFTirlA_hvHG2LUC9wsQ-emeeZeYy9RqgQUL47VLfz6MaxqgFFBbIC3D5hG2wbVSJK-ZRtAFVbtq1QZ-xFSgcAaKDhz9lZLTOiVXLDfn2JdOONt0vpfDdb6orr3UVh_OT2oXOUikjpGHxXjCFSceduQgxzGpbC9BPF_OrNUEzR-HQcMstMLvhiujX-b40H6f1SHKML8THhJXvWmyHRq_v7nH3_cPXt8rrcff746fJiV1ouYCp7LlQP1kArSXKFuO05cGUkoagtdNgLRIESsjewJKlGI6UVnPO65b3dnrO3J91jDD9nSpMeXbI05I9QdqWxEVjjev4HFBVHlQPNUH6C2hhSitTrbHI0cdEIeu1KH_SpK712pUHq3FWmvbmfMO9H6v6QHsrJgPcnAOVI7hxFnawjn4N0keyku-D-NeGxgB2cd9YMP2ihdAhzzO1lLzrVGvTXdV_WdUEBgI2qt78BffK-DA</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Higgins, Rob</creator><creator>Lowe, David</creator><creator>Daga, Sunil</creator><creator>Hathaway, Mark</creator><creator>Williams, C</creator><creator>Lam, F.T</creator><creator>Kashi, Habib</creator><creator>Tan, Lam Chin</creator><creator>Imray, Chris</creator><creator>Fletcher, Simon</creator><creator>Krishnan, Nithya</creator><creator>Hart, Pat</creator><creator>Zehnder, Daniel</creator><creator>Briggs, David</creator><general>Elsevier Inc</general><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><orcidid>https://orcid.org/0000-0002-4592-8561</orcidid></search><sort><creationdate>20150801</creationdate><title>Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation</title><author>Higgins, Rob ; Lowe, David ; Daga, Sunil ; Hathaway, Mark ; Williams, C ; Lam, F.T ; Kashi, Habib ; Tan, Lam Chin ; Imray, Chris ; Fletcher, Simon ; Krishnan, Nithya ; Hart, Pat ; Zehnder, Daniel ; Briggs, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-f459f0ca086e649113f4049a6e152c0d1f51151606890ce6e21a66c5444284fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Allergy and Immunology</topic><topic>Antibody Formation - immunology</topic><topic>Antibody incompatible kidney transplantation</topic><topic>Antibody mediated rejection</topic><topic>Antibody Specificity - immunology</topic><topic>Female</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - therapy</topic><topic>HLA antibodies</topic><topic>HLA Antigens - immunology</topic><topic>HLA Class 1</topic><topic>HLA Class 2</topic><topic>Humans</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Isoantibodies - blood</topic><topic>Isoantibodies - immunology</topic><topic>Kidney Transplantation - adverse effects</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Patient Outcome Assessment</topic><topic>Plasmapheresis - methods</topic><topic>Pregnancy</topic><topic>Time Factors</topic><topic>Transfusion</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Higgins, Rob</creatorcontrib><creatorcontrib>Lowe, David</creatorcontrib><creatorcontrib>Daga, Sunil</creatorcontrib><creatorcontrib>Hathaway, Mark</creatorcontrib><creatorcontrib>Williams, C</creatorcontrib><creatorcontrib>Lam, F.T</creatorcontrib><creatorcontrib>Kashi, Habib</creatorcontrib><creatorcontrib>Tan, Lam Chin</creatorcontrib><creatorcontrib>Imray, Chris</creatorcontrib><creatorcontrib>Fletcher, Simon</creatorcontrib><creatorcontrib>Krishnan, Nithya</creatorcontrib><creatorcontrib>Hart, Pat</creatorcontrib><creatorcontrib>Zehnder, Daniel</creatorcontrib><creatorcontrib>Briggs, David</creatorcontrib><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><jtitle>Human immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Higgins, Rob</au><au>Lowe, David</au><au>Daga, Sunil</au><au>Hathaway, Mark</au><au>Williams, C</au><au>Lam, F.T</au><au>Kashi, Habib</au><au>Tan, Lam Chin</au><au>Imray, Chris</au><au>Fletcher, Simon</au><au>Krishnan, Nithya</au><au>Hart, Pat</au><au>Zehnder, Daniel</au><au>Briggs, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation</atitle><jtitle>Human immunology</jtitle><addtitle>Hum Immunol</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>76</volume><issue>8</issue><spage>546</spage><epage>552</epage><pages>546-552</pages><issn>0198-8859</issn><eissn>1879-1166</eissn><abstract>Abstract Acute antibody mediated rejection after HLA-specific antibody incompatible renal transplantation is related to donor specific HLA antibody (DSA) levels. DSA levels may rise sharply after transplant, and aim of this study was to examine changes in DSA levels, particularly according to the primary sensitising event. Changes in 220 HLA specificities in 64 patients over the first 30 days after transplantation were evaluated using microbead assays. The greatest increase from pre-treatment to peak DSA levels was seen in pregnancy-stimulated specificities, median (IQR) increase in MFI of 1981 (94-5870). The next highest increase was for those sensitised by transplant with repeat HLA epitope mismatch, at 546 (-308-2698) ( p < 0.01). The difference was especially marked when the pre-treatment antibody level was low; with pre-treatment MFI <1000, peak level was >1000 in 19/26 (73%) of pregnancy stimulated specificities, compared with 9/29 (31%) for all others ( p < 0.001). DSA production to specificities stimulated by previous pregnancy was marked, even from very low pre-transplant levels. By contrast, there was a lower rate of antibody resynthesis to specificities repeated from previous transplants, both at antigen and epitope levels.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26116896</pmid><doi>10.1016/j.humimm.2015.06.013</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-4592-8561</orcidid></addata></record> |
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| subjects | Adult Aged Allergy and Immunology Antibody Formation - immunology Antibody incompatible kidney transplantation Antibody mediated rejection Antibody Specificity - immunology Female Graft Rejection - immunology Graft Rejection - therapy HLA antibodies HLA Antigens - immunology HLA Class 1 HLA Class 2 Humans Immunosuppressive Agents - therapeutic use Isoantibodies - blood Isoantibodies - immunology Kidney Transplantation - adverse effects Male Middle Aged Patient Outcome Assessment Plasmapheresis - methods Pregnancy Time Factors Transfusion Young Adult |
| title | Pregnancy-induced HLA antibodies respond more vigorously after renal transplantation than antibodies induced by prior transplantation |
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