title: Immunosuppression Modifications Based on an Immune Response Assay: Results of a Randomized, Controlled Trial.
abstract: BACKGROUND
  An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results.
  
  
  METHODS
  Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution.
  
  
  RESULTS
  Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels.
  
  
  CONCLUSIONS
  Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.
authors.affiliation: 1 Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 2 Department of General Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, Bologna, Italy. 3 Clinical Unit of Microbiology, University of Bologna, Bologna, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Ravaioli
authors.forename: Flavia
authors.initials: F
authors.lastname: Neri
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lazzarotto
authors.forename: Valentina Rosa
authors.initials: VR
authors.lastname: Bertuzzo
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Gioia
authors.forename: Giacomo
authors.initials: G
authors.lastname: Stacchini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Morelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ercolani
authors.forename: Matteo
authors.initials: M
authors.lastname: Cescon
authors.forename: Angela
authors.initials: A
authors.lastname: Chiereghin
authors.forename: Massimo
authors.initials: M
authors.lastname: Del Gaudio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cucchetti
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Pinna
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D007558:Italy; D016031:Liver Transplantation / Q000009:adverse effects / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000295:instrumentation / Q000379:methods*; D009894:Opportunistic Infections / Q000276:immunology / Q000517:prevention & control; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011933:Reagent Kits, Diagnostic; D013256:Steroids / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D011933:Reagent Kits, Diagnostic; D013256:Steroids; D000255:Adenosine Triphosphate; D016559:Tacrolimus