title: Lack of clinical association and effect of peripheral WBC counts on immune cell function test in kidney transplant recipients with T-cell depleting induction and steroid-sparing maintenance therapy.
abstract: The Cylex ImmuKnow assay measures the amount of stimulated ATP production by CD4+ T-cells, and has been used clinically, trying to predict rejection and infection episodes. However, predictive values of this assay after induction therapy with steroid-sparing maintenance protocols are unclear. In this single-center cohort study, we analyzed renal transplant recipients who received T-cell depleting+/-anti-IL2 receptor antibodies and tacrolimus/mycophenolate maintenance without steroids. A total of 4224 ImmuKnow levels in 306 patients were available for analysis. ImmuKnow levels (Mean ± SE) changed over time after induction therapy with a paradoxical initial increase: 419 ± 23, 461 ± 32, 519 ± 14, 411 ± 10, 344 ± 6, and 405 ± 3 for pre-transplant, 0-1 wk, 1 wk-1 mo, 1-3 mos, 3 mos-1 yr, and thereafter. This change was parallel to the evolution of peripheral WBC counts and ImmuKnow levels had weak but significant correlation with WBC counts (R(2)=0.264, P<0.0001). The levels for biopsy-proven rejection (389 ± 56) and borderline/clinical rejection (254 ± 41) were not significantly higher than the levels of quiescent patients. The levels for opportunistic infection (349 ± 48) and other infections (345 ± 27) were not significantly lower than the levels of quiescent patients. The longitudinal changes in ImmuKnow levels were not predictive of rejection or infection. In conclusion, ImmuKnow levels can vary after T-cell depleting induction therapies at various time points, even without significant clinical events. Since ImmuKnow levels seem to be affected by WBC counts, ImmuKnow results need to be interpreted with caution. The effects of leukocytosis or leukopenia caused by immunosuppressive medication on the ImmuKnow assay need further investigation.
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA. Electronic address: jsageshima@med.miami.edu.
authors: Junichiro
authors: J
authors: Sageshima
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Gaetano
authors: G
authors: Ciancio
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Linda
authors: L
authors: Chen
authors: Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Takehiko
authors: T
authors: Dohi
authors: Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Ashraf
authors: A
authors: El-Hinnawi
authors: Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Siegfredo
authors: S
authors: Paloyo
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Jeffrey J
authors: JJ
authors: Gaynor
authors: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Adela
authors: A
authors: Mattiazzi
authors: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Giselle
authors: G
authors: Guerra
authors: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Warren
authors: W
authors: Kupin
authors: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: David
authors: D
authors: Roth
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: Phillip
authors: P
authors: Ruiz
authors: Division of Kidney and Pancreas Transplantation, Dewitt Daughtry Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; Miami Transplant Institute at the Jackson Memorial Hospital and University of Miami, Miami, FL, USA.
authors: George W
authors: GW
authors: Burke
mesh_terms: D000328:Adult; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D016030:Kidney Transplantation; D007958:Leukocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents
keywords: Antibody therapy; Cylex; ImmuKnow; Infection; Kidney transplant; Rejection