Complement gene expression in human cardiac allograft biopsies as a correlate of histologic grade of injury.
Complement activation contributes to antibody-mediated allograft rejection, but increasing evidence also implicates complement proteins produced locally within the graft, in part by infiltrating mononuclear cells, as important mediators of tissue injury. To test this concept in transplant recipients, we evaluated complement, complement regulator, and T cell/proinflammatory marker gene expression by quantitative real-time polymerase chain reaction in 71 archived heart transplant biopsies and correlated the results with the histologic grade of rejection. Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies. The grade 3 rejections also contained significantly higher amounts of CD3, interferon gamma, perforin, and granzyme B genes. In addition to providing supportive evidence for a pathogenic role of graft-derived complement in human heart transplant injury, these correlations suggest that molecular profiling of complement gene expression could be useful in the diagnosis of human allograft rejection.
Keslar
Karen
K
Department of Immunology, The Cleveland Clinic, Cleveland, OH, USA.
Rodriguez
E Rene
ER
Tan
Carmela D
CD
Starling
Randall C
RC
Heeger
Peter S
PS
D001706:Biopsy; D017252:CD3 Complex / Q000378:metabolism; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D011415:Complement Factor B / Q000235:genetics / Q000378:metabolism; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006084:Graft Rejection / Q000378:metabolism; D053804:Granzymes / Q000378:metabolism; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D054353:Perforin / Q000378:metabolism; D011414:Properdin / Q000235:genetics / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
C488033:C5AR1 protein, human; D017252:CD3 Complex; D003176:Complement C3; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D011414:Properdin; D054353:Perforin; D007371:Interferon-gamma; D003165:Complement System Proteins; D053804:Granzymes; D011415:Complement Factor B