title: Serum Cytokines as Biomarkers in Islet Cell Transplantation for Type 1 Diabetes.
abstract: BACKGROUND
  Islet cell transplantation holds a potential cure for type 1 diabetes, but many islet recipients do not reach long-lasting insulin independence. In this exploratory study, we investigated whether serum cytokines, chemokines and adipokines are associated with the clinical outcome of islet transplantation.
  
  
  METHODS
  Thirteen islet transplant patients were selected on basis of good graft function (reaching insulin independence) or insufficient engraftment (insulin requiring) from our cohort receiving standardized grafts and immune suppressive therapy. Patients reaching insulin independence were divided in those with continued (>12 months) versus transient (<6 months) insulin independence. A panel of 94 proteins including cytokines and adipokines was measured in sera taken before and at one year after transplantation using a validated multiplex immunoassay platform.
  
  
  RESULTS
  Ninety serum proteins were detectable in concentrations varying markedly among patients at either time point. Thirteen markers changed after transplantation, while another seven markers changed in a clinical subpopulation. All other markers remained unaffected after transplantation under generalized immunosuppression. Patterns of cytokines could distinguish good graft function from insufficient function including IFN-α, LIF, SCF and IL-1RII before and after transplantation, by IL-16, CCL3, BDNF and M-CSF only before and by IL-22, IL-33, KIM-1, S100A12 and sCD14 after transplantation. Three other proteins (Leptin, Cathepsin L and S100A12) associated with loss of temporary graft function before or after transplantation.
  
  
  CONCLUSIONS
  Distinct cytokine signatures could be identified in serum that predict or associate with clinical outcome. These serum markers may help guiding patient selection and choice of immunotherapy, or act as novel drug targets in islet transplantation.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: Cornelis R
authors.initials: CR
authors.lastname: van der Torren
authors.affiliation: Department of Pediatric Immunology, Department of Pediatric Endocrinology and Laboratory of Translational Immunology and Multiplex Core Facility, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
authors.forename: Annemarie A
authors.initials: AA
authors.lastname: Verrijn Stuart
authors.affiliation: Dept. of Endocrinology, University Hospital, Katholieke Universiteit Leuven, 3000, Leuven, Belgium.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: DaHae
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Pediatric Immunology, Department of Pediatric Endocrinology and Laboratory of Translational Immunology and Multiplex Core Facility, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: Meerding
authors.affiliation: Diabetes Research Center and Academic Hospital, Free University-Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: Ursule
authors.initials: U
authors.lastname: van de Velde
authors.affiliation: Diabetes Research Center and Academic Hospital, Free University-Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
authors.affiliation: Dept. of Endocrinology, University Hospital, Katholieke Universiteit Leuven, 3000, Leuven, Belgium.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.affiliation: Diabetes Research Center and Academic Hospital, Free University-Vrije Universiteit Brussel (VUB), 1090, Brussels, Belgium.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
authors.affiliation: Department of Pediatric Immunology, Department of Pediatric Endocrinology and Laboratory of Translational Immunology and Multiplex Core Facility, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 CX, Utrecht, The Netherlands.
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands.|Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes.
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
mesh_terms: D054392:Adipokines / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D018925:Chemokines / Q000378:metabolism; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000628:therapy*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D007166:Immunosuppressive Agents; D007328:Insulin