title: Prospective Monitoring of Donor-specific Anti-HLA Antibodies After Intestine/Multivisceral Transplantation: Significance of De Novo Antibodies.
abstract: BACKGROUND
  Presence of circulating donor-specific antibodies (DSA) may be associated with worse clinical outcomes after intestine/multivisceral transplantation.
  
  
  METHODS
  In 79 intestine/multivisceral recipients, sera were prospectively screened for DSA by Luminex Single antigen test at 1, 3, 6, 9, 12, 18, 24, and 36 months after transplantation. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus-prednisone maintenance. C4d staining was performed retrospectively on biopsies in patients that developed acute rejection (AR).
  
  
  RESULTS
  Twenty-two (28%) patients developed de novo DSA at a median posttransplant period of 3 (1-36) months. De novo DSA were observed in 10 of 40 liver-including and 12 of 39 liver-excluding transplants (P = 0.57). Occurrence of AR was slightly higher in patients with de novo DSA (45% vs 33%, respectively; P = 0.41). Similarly, chronic rejection (14% vs 5%; P = 0.21) and graft loss due to AR (18% vs 7%; P = 0.14) were numerically higher in patients with de novo DSA. Only 35% patients experiencing AR had circulating de novo DSA at the time of AR. Antibody-mediated rejection was diagnosed in 6 patients based on C4d staining, of these 2 patients had circulating de novo DSA at the time of biopsy.
  
  
  CONCLUSIONS
  De novo DSA formation, particularly early in the posttransplant course may be associated with trends toward worse outcomes. However, its significance in the pathophysiology of AR remains uncertain. Studies focusing mechanisms of DSA-related graft injury and intragraft DSA detection might provide further insight into this issue.
authors.affiliation: 1 Transplant Division, Department of Surgery, Indiana University School of Medicine, IN, Indiana. 2 Department of Pathology, Indiana University School of Medicine, Indianapolis, IN. 3 Department of Transplant Immunology, Indiana University School of Medicine, Indianapolis, IN.
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Kubal
authors.forename: Richard
authors.initials: R
authors.lastname: Mangus
authors.forename: Romil
authors.initials: R
authors.lastname: Saxena
authors.forename: Andrew
authors.initials: A
authors.lastname: Lobashevsky
authors.forename: Nancy
authors.initials: N
authors.lastname: Higgins
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fridell
authors.forename: A Joseph
authors.initials: AJ
authors.lastname: Tector
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015935:Complement C4b / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007422:Intestines / Q000637:transplantation*; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D010446:Peptide Fragments / Q000378:metabolism; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d