An increase in myeloid-related protein serum levels precedes acute renal allograft rejection.
Upon interaction with activated endothelium, monocytes and neutrophils form complexes of myeloid-related protein 8 (MRP8) (S100A8) and MRP14 (S100A9), two members of the calcium-binding S100 family that are secreted during transendothelial migration. In a pilot study of 20 renal transplant recipients and a validation study of 36 renal transplant recipients, MRP8/14 serum levels were measured with an enzyme-linked immunosorbent assay for 28 d, associated with C-reactive protein and creatinine serum levels, and grouped according to biopsy-proven acute rejection. Serum levels of MRP8/14 but not C-reactive protein were significantly increased for several days during the first 2 wk for the acute rejection groups in both studies (P < 0.005, on day 6 after transplantation). As determined by using receiver operating characteristic curves, the optimal cutoff for 100% specificity and high sensitivity (67%) for acute rejection on day 6 after transplantation was calculated to be 4.2 microg/ml for MRP8/14 in the pilot study; this value was confirmed in the validation study. Positive MRP8/14 serum levels preceded acute rejection episodes by a median of 5 d. A 3-d course of intravenous methylprednisolone therapy reduced prerejection MRP8/14 serum levels from 5.7 microg/ml to 3.3 microg/ml (P < 0.05). All MRP8/14 serum levels were below the cutoff during urinary tract infections, delayed graft function, or cytomegalovirus infections, and these values did not differ significantly from control values. It is concluded that the MRP8/14 complex is a very early serum marker suitable for monitoring of acute rejection with high sensitivity and specificity.
Burkhardt
Klaus
K
Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
Radespiel-Tröger
Martin
M
Institute for Medical Information, Biometrics, and Epidemiology, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
Rupprecht
Harald D
HD
Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
Goppelt-Struebe
Margarete
M
Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
Riess
Regine
R
Pathology Institute, Nuremberg Clinic South, Nuremberg, Germany.
Renders
Lutz
L
Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
Hauser
Ingeborg A
IA
Medical Clinic IV, Nephrology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Kunzendorf
Ulrich
U
Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany.
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000943:Antigens, Differentiation / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002135:Calcium-Binding Proteins / Q000097:blood*; D040501:Calgranulin A; D040502:Calgranulin B; D003586:Cytomegalovirus Infections / Q000097:blood; D005938:Glucocorticoids / Q000627:therapeutic use; D006084:Graft Rejection / Q000097:blood*; D006680:HLA Antigens / Q000032:analysis; D006648:Histocompatibility; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008137:Longitudinal Studies; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D009418:S100 Proteins / Q000097:blood*; D013997:Time Factors; D014184:Transplantation, Homologous; D014552:Urinary Tract Infections / Q000097:blood
D000943:Antigens, Differentiation; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D005938:Glucocorticoids; D006680:HLA Antigens; D009418:S100 Proteins; D002097:C-Reactive Protein; D008775:Methylprednisolone