title: Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.
abstract: Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF < BL < AR. Relying on serum analysis only, multivariate logistic regression (logit link function) yielded a prognostic score for prediction of rejection with 75.0% sensitivity and 69.2% specificity. Patients with rejection showed markedly higher pre-transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated.
authors.affiliation: Transplant Laboratory, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Florian W R
authors.initials: FW
authors.lastname: Vondran
authors.forename: Kai
authors.initials: K
authors.lastname: Timrott
authors.forename: Sonja
authors.initials: S
authors.lastname: Kollrich
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Steinhoff
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaltenborn
authors.forename: Harald
authors.initials: H
authors.lastname: Schrem
authors.forename: Juergen
authors.initials: J
authors.lastname: Klempnauer
authors.forename: Frank
authors.initials: F
authors.lastname: Lehner
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwinzer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D018960:Hyaluronan Receptors / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D017730:Ki-1 Antigen / Q000097:blood; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000601:surgery; D016030:Kidney Transplantation; D019520:Living Donors; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care; D011237:Predictive Value of Tests; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D017730:Ki-1 Antigen
keywords: CD161; acute rejection; kidney transplantation; sCD25; sCD30; sCD44