title: Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.
abstract: BACKGROUND
  Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates.
  
  
  METHODS
  In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization.
  
  
  RESULTS
  Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant.
  
  
  CONCLUSIONS
  The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.
authors.affiliation: Transplant Immunology Laboratory, Indiana University Health Transplant Center, Indianapolis, IN 46202-1218, USA. alobashe@iuhealth.org
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lobashevsky
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Higgins
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Rosner
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Mujtaba
authors.forename: William C
authors.initials: WC
authors.lastname: Goggins
authors.forename: Tim E
authors.initials: TE
authors.lastname: Taber
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D000918:Antibody Specificity; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006680:HLA Antigens; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000069283:Rituximab; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D000069283:Rituximab