Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation.
Post-transplant circulating anti-human leukocyte antigens (HLA)-antibodies and C4d in allograft biopsies may be important in chronic rejection in renal transplant recipients (RTR). We determined the prevalence and significance of anti-HLA-antibodies and donor-specific antibodies (DSA). Sera were collected from 251 RTR >6 months post-transplant. Sera were tested using enzyme-linked immunosorbent assay (ELISA) screening for anti-HLA antibodies. Positive sera were retested with ELISA-specific panel for antibody specificity. A 11.2% of patients had anti-HLA antibodies and 4.4% had DSA. Anti-HLA antibodies were significantly associated with pretransplant sensitization, acute rejection and in multivariate analysis, higher serum creatinine (2.15 +/- 0.98 vs. 1.57 +/- 0.69 mg/dl in negative anti-HLA antibodies group). Allograft biopsies performed in a subset of patients with anti-HLA antibodies revealed that 66% had C4d in peritubular capillaries (0% in patients without antibodies). Anti-HLA antibodies were associated with a worse allograft function and in situ evidence of anti-donor humoral alloreactivity. Long-term RTR with an increase in creatinine could be screened for anti-HLA antibodies and C4d in biopsy.
Cardarelli
Francesca
F
Clinica Medica e Nefrologia, Universita degli Studi di Parma, Parma, Italy. cardarelli.francesca@asmn.re.it
Pascual
Manuel
M
Tolkoff-Rubin
Nina
N
Delmonico
Francis L
FL
Wong
Waichi
W
Schoenfeld
David A
DA
Zhang
Hui
H
Cosimi
A Benedict
AB
Saidman
Susan L
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015935:Complement C4b / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors
D006680:HLA Antigens; D007518:Isoantibodies; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d