{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:41:57Z","timestamp":1790638917617,"version":"4.1.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2012,5,29]],"date-time":"2012-05-29T00:00:00Z","timestamp":1338249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>There is a paucity of data concerning the correlation of complement component 4d (C4d) staining in liver allografts and antibody-mediated rejection. Data about the location and character of C4d deposits in native and allograft liver tissues are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh-frozen liver allograft biopsy samples and native livers, documented the pattern of C4d IF staining, and correlated the findings with the presence of donor-specific alloantibodies (DSAs). A linear\/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsy samples obtained after transplantation from patients with positive crossmatch and detectable donor-specific alloantibody (pos-XM\/DSA) findings. None of the 59 tested biopsy samples from patients with negative crossmatch and detectable donor-specific alloantibody (neg-XM\/DSA) findings were C4d-positive (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). No significant association was found between pos-XM\/DSA and C4d IF staining in other nonsinusoidal liver compartments. To compare the results of sinusoidal C4d staining with IF and 2 immunohistochemistry (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsy samples in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC findings were negative for 17 of the 19 biopsy samples; 2 showed weak and focal staining, and both patients had pos-XM\/DSA findings. Portal vein endothelium staining was present in only 1 IF-stained biopsy sample (pos-XM\/DSA) but in 11 IHC-stained biopsy samples (2 of the 11 samples had neg-XM\/DSA findings). We conclude that sinusoidal C4d deposits detected by IF in frozen tissue samples from liver allograft recipients correlate with the presence of DSAs and an antibody-mediated alloresponse. These observations are similar to findings reported for other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/lt.23403","type":"journal-article","created":{"date-parts":[[2012,2,2]],"date-time":"2012-02-02T10:36:42Z","timestamp":1328179002000},"page":"641-658","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":49,"title":["Sinusoidal C4d deposits in liver allografts indicate an antibody-mediated response: Diagnostic considerations in the evaluation of liver allografts"],"prefix":"10.1097","volume":"18","author":[{"given":"Tomasz","family":"Kozlowski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Andreoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Schmitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Hideo Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Nickeleit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-5-20250124","doi-asserted-by":"crossref","first-page":"5159","DOI":"10.1055\/s-2007-1007376","article-title":"Immunopathology of antibodies as effectors of orthotopic liver allograft rejection.","volume":"12","author":"Demetris","year":"1992","journal-title":"Semin Liver Dis"},{"key":"R2-5-20250124","doi-asserted-by":"crossref","first-page":"742750","DOI":"10.1016\/S0198-8859(02)00429-9","article-title":"Is presensitization relevant to liver transplantation outcome?","volume":"63","author":"Bishara","year":"2002","journal-title":"Hum Immunol"},{"key":"R3-5-20250124","doi-asserted-by":"crossref","first-page":"357368","DOI":"10.1002\/lt.22233","article-title":"Liver allograft antibodymediated rejection with demonstration of sinusoidal C4d staining and circulating donorspecific antibodies.","volume":"17","author":"Kozlowski","year":"2011","journal-title":"Liver Transpl"},{"key":"R4-5-20250124","doi-asserted-by":"crossref","first-page":"13451352","DOI":"10.1002\/hep.1840210519","article-title":"Immunoglobulin G lymphocytotoxic antibodies in clinical liver transplantation: studies toward further defining their significance.","volume":"21","author":"Manez","year":"1995","journal-title":"Hepatology"},{"key":"R5-5-20250124","doi-asserted-by":"crossref","first-page":"27782785","DOI":"10.1111\/j.1600-6143.2005.01074.x","article-title":"Antibodymediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products C4d and C3d as markers.","volume":"5","author":"Rodriguez","year":"2005","journal-title":"Am J Transplant"},{"key":"R6-5-20250124","doi-asserted-by":"crossref","first-page":"423428","DOI":"10.1111\/j.1600-6143.2005.01185.x","article-title":"Antibodymediated rejection of a pancreas allograft.","volume":"6","author":"Melcher","year":"2006","journal-title":"Am J Transplant"},{"key":"R7-5-20250124","doi-asserted-by":"crossref","first-page":"11431154","DOI":"10.1034\/j.1600-6143.2003.00152.x","article-title":"Use of C4d as a diagnostic adjunct in lung allograft biopsies.","volume":"3","author":"Magro","year":"2003","journal-title":"Am J 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Pathol"},{"key":"R14-5-20250124","doi-asserted-by":"crossref","first-page":"624633","DOI":"10.1111\/j.1399-0012.2006.00528.x","article-title":"Characterization of CD4, CD8, CD56 positive lymphocytes and C4d deposits to distinguish acute cellular rejection from recurrent hepatitis C in postliver transplant biopsies.","volume":"20","author":"Jain","year":"2006","journal-title":"Clin Transplant"},{"key":"R16-5-20250124","doi-asserted-by":"crossref","first-page":"8793","DOI":"10.1007\/s00428-005-1245-z","article-title":"Portal capillary C4d deposits and increased infiltration by macrophages indicate humorally mediated mechanisms in acute cellular liver allograft rejection.","volume":"447","author":"Dankof","year":"2005","journal-title":"Virchows Arch"},{"key":"R17-5-20250124","doi-asserted-by":"crossref","first-page":"30223029","DOI":"10.1111\/j.1600-6143.2006.01554.x","article-title":"Isolated donor specific alloantibodymediated rejection after ABO compatible liver 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