High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation

Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk...

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Veröffentlicht in:Transplantation 2011-05, Vol.91 (9), p.1044-1049
Hauptverfasser: CARROLL, Katherine E, DEAN, Melinda M, HEATLEY, Susan L, MEEHAN, Aislin C, MIFSUD, Nicole A, KOTSIMBOS, Tom C, SNELL, Greg I, WESTALL, Glen P
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container_end_page 1049
container_issue 9
container_start_page 1044
container_title Transplantation
container_volume 91
creator CARROLL, Katherine E
DEAN, Melinda M
HEATLEY, Susan L
MEEHAN, Aislin C
MIFSUD, Nicole A
KOTSIMBOS, Tom C
SNELL, Greg I
WESTALL, Glen P
description Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P
doi_str_mv 10.1097/TP.0b013e318212c7d6
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Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P&lt;0.05). LTR who developed BOS or died during the study period had higher plasma MBL levels at 6 and 12 months posttransplant (P ≤ 0.05) compared with LTR with stable graft function. MBL was not routinely detected in the lung allograft; however if present in the BAL at 3 and 6 months posttransplant, it was associated with the later development of BOS (P&lt;0.05). Plasma MBL levels increase after lung transplantation and persistently increased MBL levels are associated with poor long-term outcomes.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e318212c7d6</identifier><identifier>PMID: 21394075</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams &amp; Wilkins</publisher><subject>Adolescent ; Adult ; Aged ; Alternative pathway ; Alveoli ; Biological and medical sciences ; bronchiolitis obliterans ; Bronchiolitis Obliterans - etiology ; Bronchoalveolar Lavage Fluid - chemistry ; Bronchus ; Cohort Studies ; Complement activation ; Donors ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Genotype ; Genotypes ; Genotyping ; Graft rejection ; Graft Rejection - etiology ; Humans ; Immune system ; Infection ; Intensive care units ; Longitudinal Studies ; Lung Transplantation - adverse effects ; Lung Transplantation - physiology ; Male ; Mannose-binding lectin ; Mannose-Binding Lectin - blood ; Mannose-Binding Lectin - genetics ; Mannose-Binding Lectin - metabolism ; Medical sciences ; Middle Aged ; Mortality ; Mutation ; Peripheral blood mononuclear cells ; Pneumonia - etiology ; Retrospective Studies ; Serum levels ; Surgery (general aspects). Transplantations, organ and tissue grafts. 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Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P&lt;0.05). LTR who developed BOS or died during the study period had higher plasma MBL levels at 6 and 12 months posttransplant (P ≤ 0.05) compared with LTR with stable graft function. MBL was not routinely detected in the lung allograft; however if present in the BAL at 3 and 6 months posttransplant, it was associated with the later development of BOS (P&lt;0.05). Plasma MBL levels increase after lung transplantation and persistently increased MBL levels are associated with poor long-term outcomes.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Alternative pathway</subject><subject>Alveoli</subject><subject>Biological and medical sciences</subject><subject>bronchiolitis obliterans</subject><subject>Bronchiolitis Obliterans - etiology</subject><subject>Bronchoalveolar Lavage Fluid - chemistry</subject><subject>Bronchus</subject><subject>Cohort Studies</subject><subject>Complement activation</subject><subject>Donors</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Genotyping</subject><subject>Graft rejection</subject><subject>Graft Rejection - etiology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Infection</subject><subject>Intensive care units</subject><subject>Longitudinal Studies</subject><subject>Lung Transplantation - adverse effects</subject><subject>Lung Transplantation - physiology</subject><subject>Male</subject><subject>Mannose-binding lectin</subject><subject>Mannose-Binding Lectin - blood</subject><subject>Mannose-Binding Lectin - genetics</subject><subject>Mannose-Binding Lectin - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Mutation</subject><subject>Peripheral blood mononuclear cells</subject><subject>Pneumonia - etiology</subject><subject>Retrospective Studies</subject><subject>Serum levels</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue Donors</subject><subject>Tissue, organ and graft immunology</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90cGOFCEQBmBiNO7s6hOYGC5GL70CBQMcx43umozZOYzx2KHpYhfT04xAm_j2YnbUxIMnDvX9VaSKkBecXXJm9dv97pINjAMCN4ILr8f1I7LiCmS3ZoY9JivGJO84gD4j56V8ZYwp0PopORMcrGRarchwE-_u6Ra_41RoCvSTm-dUsHsX5zHOd63ia5zpJiPdlJJ8dBVH-iXWe7pLKdPbpfp0wEI3oWKm26Vl9tnN5Ti5uboa0_yMPAluKvj89F6Qzx_e769uuu3t9cerzbbzkovaGeNGHSCw9WCDAq8kuOAD90MYhBBWWu4586NFjWp0DiygF8p6DYZLqeCCvH7oe8zp24Kl9odYPE7tI5iW0hvNGRNasCbf_Fc2Z4xUUthG4YH6nErJGPpjjgeXfzTU_zpDv9_1_56hpV6eBizDAcc_md97b-DVCbji3RTaxnwsf53kyoCU8BMg7JCY</recordid><startdate>20110515</startdate><enddate>20110515</enddate><creator>CARROLL, Katherine E</creator><creator>DEAN, Melinda M</creator><creator>HEATLEY, Susan L</creator><creator>MEEHAN, Aislin C</creator><creator>MIFSUD, Nicole A</creator><creator>KOTSIMBOS, Tom C</creator><creator>SNELL, Greg I</creator><creator>WESTALL, Glen P</creator><general>Lippincott Williams &amp; Wilkins</general><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>7X8</scope></search><sort><creationdate>20110515</creationdate><title>High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation</title><author>CARROLL, Katherine E ; DEAN, Melinda M ; HEATLEY, Susan L ; MEEHAN, Aislin C ; MIFSUD, Nicole A ; KOTSIMBOS, Tom C ; SNELL, Greg I ; WESTALL, Glen P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-88ad7f3f06b9f53c543afcf1cbfb2229491c10cd9e7e5daa393ec259c73814453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Alternative pathway</topic><topic>Alveoli</topic><topic>Biological and medical sciences</topic><topic>bronchiolitis obliterans</topic><topic>Bronchiolitis Obliterans - etiology</topic><topic>Bronchoalveolar Lavage Fluid - chemistry</topic><topic>Bronchus</topic><topic>Cohort Studies</topic><topic>Complement activation</topic><topic>Donors</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. 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Graft diseases</topic><topic>Tissue Donors</topic><topic>Tissue, organ and graft immunology</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CARROLL, Katherine E</creatorcontrib><creatorcontrib>DEAN, Melinda M</creatorcontrib><creatorcontrib>HEATLEY, Susan L</creatorcontrib><creatorcontrib>MEEHAN, Aislin C</creatorcontrib><creatorcontrib>MIFSUD, Nicole A</creatorcontrib><creatorcontrib>KOTSIMBOS, Tom C</creatorcontrib><creatorcontrib>SNELL, Greg I</creatorcontrib><creatorcontrib>WESTALL, Glen P</creatorcontrib><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>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CARROLL, Katherine E</au><au>DEAN, Melinda M</au><au>HEATLEY, Susan L</au><au>MEEHAN, Aislin C</au><au>MIFSUD, Nicole A</au><au>KOTSIMBOS, Tom C</au><au>SNELL, Greg I</au><au>WESTALL, Glen P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2011-05-15</date><risdate>2011</risdate><volume>91</volume><issue>9</issue><spage>1044</spage><epage>1049</epage><pages>1044-1049</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Mannose-binding lectin (MBL) is a key molecule of the innate immune system and, in addition to the classical and alternative pathways, a principle driver of complement activation. Genetic mutations of MBL are common, result in low serum levels of MBL, and are associated with increased infection risk in solid-organ transplant recipients. We performed a retrospective study of MBL2 genotype and plasma and bronchoalveolar lavage (BAL) MBL levels in 37 lung transplant recipients (LTR). Plasma MBL levels were measured pretransplant and both plasma and BAL MBL levels were measured at 3, 6, and 12 months after lung transplantation. MBL2 genotyping was performed on recipient and donor peripheral blood mononuclear cells. Clinical variables analyzed included primary graft dysfunction, intensive care unit stay, acute allograft rejection, infection, bronchiolitis obliterans syndrome (BOS), and mortality. Plasma MBL levels posttransplant were predicted by recipient, and not donor MBL2 genotype. Compared with pretransplant levels, plasma MBL was significantly increased at 3, 6, and 12 months posttransplant (P&lt;0.05). LTR who developed BOS or died during the study period had higher plasma MBL levels at 6 and 12 months posttransplant (P ≤ 0.05) compared with LTR with stable graft function. MBL was not routinely detected in the lung allograft; however if present in the BAL at 3 and 6 months posttransplant, it was associated with the later development of BOS (P&lt;0.05). Plasma MBL levels increase after lung transplantation and persistently increased MBL levels are associated with poor long-term outcomes.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>21394075</pmid><doi>10.1097/TP.0b013e318212c7d6</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Aged
Alternative pathway
Alveoli
Biological and medical sciences
bronchiolitis obliterans
Bronchiolitis Obliterans - etiology
Bronchoalveolar Lavage Fluid - chemistry
Bronchus
Cohort Studies
Complement activation
Donors
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genotype
Genotypes
Genotyping
Graft rejection
Graft Rejection - etiology
Humans
Immune system
Infection
Intensive care units
Longitudinal Studies
Lung Transplantation - adverse effects
Lung Transplantation - physiology
Male
Mannose-binding lectin
Mannose-Binding Lectin - blood
Mannose-Binding Lectin - genetics
Mannose-Binding Lectin - metabolism
Medical sciences
Middle Aged
Mortality
Mutation
Peripheral blood mononuclear cells
Pneumonia - etiology
Retrospective Studies
Serum levels
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Tissue Donors
Tissue, organ and graft immunology
Treatment Outcome
Young Adult
title High Levels of Mannose-Binding Lectin Are Associated With Poor Outcomes After Lung Transplantation
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