The clinical and molecular significance of C4d staining patterns in renal allografts
We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays. Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using...
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| Veröffentlicht in: | Transplantation 2013-02, Vol.95 (4), p.580-588 |
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| creator | Hayde, Nicole Bao, Yi Pullman, James Ye, Bin Calder, Brent R Chung, Monica Schwartz, Daniel Alansari, Ahmed de Boccardo, Graciela Ling, Min Akalin, Enver |
| description | We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays.
Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays.
Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P |
| doi_str_mv | 10.1097/TP.0b013e318277b2e2 |
| format | Article |
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Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays.
Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P<0.001). The glomerulitis, interstitial inflammation, and peritubular capillaritis scores were also significantly higher in minimal (0.88, 1.25, and 1.5) and focal/diffuse PTC C4d+ biopsies (0.65, 1.41, and 1.5), compared with C4d-negative biopsies (0.25, 079, and 0.34), respectively. There were no differences in the DSA frequency, AMR rate, or Banff scores between isolated glomerular C4d+ and C4d-negative patients. Although both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, interferon-gamma and rejection-induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis-based transcripts, there was no activation of immune-response-related genes in isolated glomerular C4d+ biopsies.
Minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR, circulating DSAs and immune-response-related gene activation.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/TP.0b013e318277b2e2</identifier><identifier>PMID: 23274969</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Antibodies ; Biomarkers - analysis ; Biopsy ; Capillaries - immunology ; Capillaries - pathology ; Cell activation ; Chi-Square Distribution ; Complement C4b - analysis ; Complement C4b - genetics ; Cytotoxicity ; DNA microarrays ; Female ; gamma -Interferon ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation ; Graft Rejection - immunology ; Graft Rejection - pathology ; Histocompatibility ; Histocompatibility antigen HLA ; HLA Antigens - immunology ; Humans ; Immunohistochemistry ; Inflammation ; Isoantibodies - blood ; Kaplan-Meier Estimate ; Kidney - blood supply ; Kidney - immunology ; Kidney - pathology ; Kidney - surgery ; Kidney Glomerulus - immunology ; Kidney Glomerulus - pathology ; Kidney transplantation ; Kidney Transplantation - immunology ; Kidney Transplantation - mortality ; Lymphocytes T ; Male ; Middle Aged ; Odds Ratio ; Oligonucleotide Array Sequence Analysis ; Paraffin ; Peptide Fragments - analysis ; Peptide Fragments - genetics ; RNA, Messenger - analysis ; Transcription activation ; Treatment Outcome</subject><ispartof>Transplantation, 2013-02, Vol.95 (4), p.580-588</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c449t-431c32ba25a3acc11a506ceafbaa3ae839d84191ccb03c4a7de60dfdad53ce5a3</citedby><cites>FETCH-LOGICAL-c449t-431c32ba25a3acc11a506ceafbaa3ae839d84191ccb03c4a7de60dfdad53ce5a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23274969$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hayde, Nicole</creatorcontrib><creatorcontrib>Bao, Yi</creatorcontrib><creatorcontrib>Pullman, James</creatorcontrib><creatorcontrib>Ye, Bin</creatorcontrib><creatorcontrib>Calder, Brent R</creatorcontrib><creatorcontrib>Chung, Monica</creatorcontrib><creatorcontrib>Schwartz, Daniel</creatorcontrib><creatorcontrib>Alansari, Ahmed</creatorcontrib><creatorcontrib>de Boccardo, Graciela</creatorcontrib><creatorcontrib>Ling, Min</creatorcontrib><creatorcontrib>Akalin, Enver</creatorcontrib><title>The clinical and molecular significance of C4d staining patterns in renal allografts</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays.
Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays.
Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P<0.001). The glomerulitis, interstitial inflammation, and peritubular capillaritis scores were also significantly higher in minimal (0.88, 1.25, and 1.5) and focal/diffuse PTC C4d+ biopsies (0.65, 1.41, and 1.5), compared with C4d-negative biopsies (0.25, 079, and 0.34), respectively. There were no differences in the DSA frequency, AMR rate, or Banff scores between isolated glomerular C4d+ and C4d-negative patients. Although both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, interferon-gamma and rejection-induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis-based transcripts, there was no activation of immune-response-related genes in isolated glomerular C4d+ biopsies.
Minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR, circulating DSAs and immune-response-related gene activation.</description><subject>Adult</subject><subject>Antibodies</subject><subject>Biomarkers - analysis</subject><subject>Biopsy</subject><subject>Capillaries - immunology</subject><subject>Capillaries - pathology</subject><subject>Cell activation</subject><subject>Chi-Square Distribution</subject><subject>Complement C4b - analysis</subject><subject>Complement C4b - genetics</subject><subject>Cytotoxicity</subject><subject>DNA microarrays</subject><subject>Female</subject><subject>gamma -Interferon</subject><subject>Gene expression</subject><subject>Gene Expression Profiling - methods</subject><subject>Gene Expression Regulation</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - pathology</subject><subject>Histocompatibility</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA Antigens - immunology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Inflammation</subject><subject>Isoantibodies - blood</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney - blood supply</subject><subject>Kidney - immunology</subject><subject>Kidney - pathology</subject><subject>Kidney - surgery</subject><subject>Kidney Glomerulus - immunology</subject><subject>Kidney Glomerulus - pathology</subject><subject>Kidney transplantation</subject><subject>Kidney Transplantation - immunology</subject><subject>Kidney Transplantation - mortality</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Odds Ratio</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Paraffin</subject><subject>Peptide Fragments - analysis</subject><subject>Peptide Fragments - genetics</subject><subject>RNA, Messenger - analysis</subject><subject>Transcription activation</subject><subject>Treatment Outcome</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkD1PwzAQhi0EoqXwC5CQR5YU2-fUyYgqvqRKdAhzdHEuJch1ip0M_HtStTAwMZ303vPcSS9j11LMpcjNXbGei0pIIJCZMqZSpE7YVKagk4XIxCmbCqFlIgHMhF3E-CGESMGYczZRoIzOF_mUFcU7ceta31p0HH3Nt50jOzgMPLYb3zbjwlviXcOXuuaxx5H1G77DvqfgI289D-T3snPdJmDTx0t21qCLdHWcM_b2-FAsn5PV69PL8n6VWK3zPtEgLagKVYqA1kqJqVhYwqbCMaAM8jrTMpfWVgKsRlPTQtRNjXUKlkZpxm4Pd3eh-xwo9uW2jZacQ0_dEEsJKkuVzPLsP6gyKpOgRxQOqA1djIGachfaLYavUopy33xZrMu_zY_WzfHBUG2p_nV-qoZvWAyAsw</recordid><startdate>20130227</startdate><enddate>20130227</enddate><creator>Hayde, Nicole</creator><creator>Bao, Yi</creator><creator>Pullman, James</creator><creator>Ye, Bin</creator><creator>Calder, Brent R</creator><creator>Chung, Monica</creator><creator>Schwartz, Daniel</creator><creator>Alansari, Ahmed</creator><creator>de Boccardo, Graciela</creator><creator>Ling, Min</creator><creator>Akalin, Enver</creator><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></search><sort><creationdate>20130227</creationdate><title>The clinical and molecular significance of C4d staining patterns in renal allografts</title><author>Hayde, Nicole ; Bao, Yi ; Pullman, James ; Ye, Bin ; Calder, Brent R ; Chung, Monica ; Schwartz, Daniel ; Alansari, Ahmed ; de Boccardo, Graciela ; Ling, Min ; Akalin, Enver</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c449t-431c32ba25a3acc11a506ceafbaa3ae839d84191ccb03c4a7de60dfdad53ce5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Antibodies</topic><topic>Biomarkers - analysis</topic><topic>Biopsy</topic><topic>Capillaries - immunology</topic><topic>Capillaries - pathology</topic><topic>Cell activation</topic><topic>Chi-Square Distribution</topic><topic>Complement C4b - analysis</topic><topic>Complement C4b - genetics</topic><topic>Cytotoxicity</topic><topic>DNA microarrays</topic><topic>Female</topic><topic>gamma -Interferon</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - pathology</topic><topic>Histocompatibility</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA Antigens - immunology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Inflammation</topic><topic>Isoantibodies - blood</topic><topic>Kaplan-Meier Estimate</topic><topic>Kidney - blood supply</topic><topic>Kidney - immunology</topic><topic>Kidney - pathology</topic><topic>Kidney - surgery</topic><topic>Kidney Glomerulus - immunology</topic><topic>Kidney Glomerulus - pathology</topic><topic>Kidney transplantation</topic><topic>Kidney Transplantation - immunology</topic><topic>Kidney Transplantation - mortality</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Odds Ratio</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Paraffin</topic><topic>Peptide Fragments - analysis</topic><topic>Peptide Fragments - genetics</topic><topic>RNA, Messenger - analysis</topic><topic>Transcription activation</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hayde, Nicole</creatorcontrib><creatorcontrib>Bao, Yi</creatorcontrib><creatorcontrib>Pullman, James</creatorcontrib><creatorcontrib>Ye, Bin</creatorcontrib><creatorcontrib>Calder, Brent R</creatorcontrib><creatorcontrib>Chung, Monica</creatorcontrib><creatorcontrib>Schwartz, Daniel</creatorcontrib><creatorcontrib>Alansari, Ahmed</creatorcontrib><creatorcontrib>de Boccardo, Graciela</creatorcontrib><creatorcontrib>Ling, Min</creatorcontrib><creatorcontrib>Akalin, Enver</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>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hayde, Nicole</au><au>Bao, Yi</au><au>Pullman, James</au><au>Ye, Bin</au><au>Calder, Brent R</au><au>Chung, Monica</au><au>Schwartz, Daniel</au><au>Alansari, Ahmed</au><au>de Boccardo, Graciela</au><au>Ling, Min</au><au>Akalin, Enver</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The clinical and molecular significance of C4d staining patterns in renal allografts</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2013-02-27</date><risdate>2013</risdate><volume>95</volume><issue>4</issue><spage>580</spage><epage>588</epage><pages>580-588</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><abstract>We investigated the clinical and molecular significance of minimal peritubular capillary (PTC) and isolated glomerular C4d+ staining using microarrays.
Two hundred fifty-five clinically indicated transplant biopsies were included in the analyses. C4d staining was performed on paraffin sections using a polyclonal rabbit anti-C4d antibody. Gene expression profiles in a subset of patients were studied using Affymetrix HuGene 1.0ST arrays.
Immunohistochemistry for C4d of 255 biopsies showed 51% C4d negative, 4% minimal PTC C4d+, 15% focal or diffuse PTC C4d+, and 31% isolated glomerular C4d+ biopsies. Patients with minimal and focal/diffuse PTC C4d+ staining had higher frequency of donor-specific anti-HLA antibodies (DSA) (67% and 82%) and antibody mediated rejection (AMR) (66% and 89%) when compared with C4d-negative biopsies (25% and 19%, respectively) (P<0.001). The glomerulitis, interstitial inflammation, and peritubular capillaritis scores were also significantly higher in minimal (0.88, 1.25, and 1.5) and focal/diffuse PTC C4d+ biopsies (0.65, 1.41, and 1.5), compared with C4d-negative biopsies (0.25, 079, and 0.34), respectively. There were no differences in the DSA frequency, AMR rate, or Banff scores between isolated glomerular C4d+ and C4d-negative patients. Although both minimal and focal/diffuse C4d+ biopsies showed increased expression of genes related to the immune response, interferon-gamma and rejection-induced, cytotoxic T cell and constitutive macrophage-associated pathogenesis-based transcripts, there was no activation of immune-response-related genes in isolated glomerular C4d+ biopsies.
Minimal PTC C4d+ staining but not isolated glomerular C4d+ staining is associated with AMR, circulating DSAs and immune-response-related gene activation.</abstract><cop>United States</cop><pmid>23274969</pmid><doi>10.1097/TP.0b013e318277b2e2</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Antibodies Biomarkers - analysis Biopsy Capillaries - immunology Capillaries - pathology Cell activation Chi-Square Distribution Complement C4b - analysis Complement C4b - genetics Cytotoxicity DNA microarrays Female gamma -Interferon Gene expression Gene Expression Profiling - methods Gene Expression Regulation Graft Rejection - immunology Graft Rejection - pathology Histocompatibility Histocompatibility antigen HLA HLA Antigens - immunology Humans Immunohistochemistry Inflammation Isoantibodies - blood Kaplan-Meier Estimate Kidney - blood supply Kidney - immunology Kidney - pathology Kidney - surgery Kidney Glomerulus - immunology Kidney Glomerulus - pathology Kidney transplantation Kidney Transplantation - immunology Kidney Transplantation - mortality Lymphocytes T Male Middle Aged Odds Ratio Oligonucleotide Array Sequence Analysis Paraffin Peptide Fragments - analysis Peptide Fragments - genetics RNA, Messenger - analysis Transcription activation Treatment Outcome |
| title | The clinical and molecular significance of C4d staining patterns in renal allografts |
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