title: Using donor-specific antibodies to monitor the need for immunosuppression.
abstract: BACKGROUND
  Experience with tolerance protocols has shown that none is perfect and that each escape from tolerance must be identified early to prevent graft failure. In addition, some test is needed for patients who are weaned off immunosuppression (IS) to forewarn of weaning failure. The usual measures of function--such as serum creatinine levels--are not sensitive enough to detect rejection in a timely manner.
  
  
  METHODS
  A study was carried out on 72 patients who received living-donor kidney transplants with clonal deletion protocol (total lymphoid irradiation or bortezomib), and followed with reduced doses of maintenance IS. Every month or every 2 months, a test was performed for donor-specific antibodies (DSA) using Luminex mixed and/or single antigen beads.
  
  
  RESULTS
  After transplantation, DSA developed in 17% of the patients at 6 months, 41% at 1 year, and 57% at 2 years, with 95% confidence limits of 10%, 28%; 30%, 55%; and 44%, 71%, respectively. Fifty-three percent of patients weaned IS to less than 10 mg prednisone daily experienced DSA within 3 months. Furthermore, prednisone dose (per 2.5 mg) and years after transplantation were inversely associated with DSA production (risk ratio 0.92 [95% confidence limits: 0.85, 0.99], and 0.70 [0.49, 1.00]).
  
  
  CONCLUSIONS
  DSA monitoring is highly effective for detecting escape from tolerance and reemergence of the immune response in weaned patients. DSA appearance was inversely proportional to the level of maintenance drugs in the weaning process. Measurement of DSA on a monthly basis is adequate for detection of the change in immune reactivity.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles, CA, USA. jhoshino@terasakilab.org
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.forename: Hugo
authors.initials: H
authors.lastname: Kaneku
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Sander
authors.initials: S
authors.lastname: Greenland
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007518:Isoantibodies / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods*; D011241:Prednisone / Q000627:therapeutic use; D016016:Proportional Hazards Models; D023001:Transplantation Tolerance
chemical_list: D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011241:Prednisone