Deleterious Impact of Donor-Specific Anti-HLA Antibodies Toward HLA-Cw and HLA-DP in Kidney Transplantation.
BACKGROUND
It is widely accepted that HLA donor-specific antibodies (DSA) are associated with antibody-mediated rejection and graft loss. However, in many transplant programs, preformed anti-HLA-Cw and anti-HLA-DP DSA are not considered in organ allocation policies because their clinical relevance is still uncertain.


METHODS
We analyzed the clinical impact of Cw/DP DSA through a retrospective study, comparing 48 patients transplanted with isolated preformed Cw/DP DSA (Cw/DP DSA group) with (i) 104 matched HLA-sensitized kidney transplant recipients with No DSA at D0 (No DSA group) and (ii) 47 kidney transplant recipients with preformed A, -B, -DR, -DQ DSA (A/B/DR/DQ DSA group).


RESULTS
A positive flow cytometry crossmatch in the Cw/DP DSA group was more frequent than in the No DSA group and as frequent as in the A/B/DR/DQDSA group. Two years after transplantation, the biopsy-proven acute rejection-free survival was worse in the Cw/DP and A/B/DR/DQ DSA groups than in the No DSA group (65%, 84%, 93%, P = 0.001 and P = 0.05, respectively). Accordingly, graft survival was lower in the Cw/DP and the A/B/DR/DQ DSA groups than in the No DSA group (87%, 89%, 95%, P = 0.02 and P = 0.1, respectively).


CONCLUSIONS
These results suggest that preformed anti-HLA-Cw and anti-HLA-DP DSA are as deleterious as anti-HLA A/B/DR/DQ DSA. It justifies their inclusion in kidney allocation programs and in immunological risk stratification algorithms.
1 Service de Néphrologie, Transplantation, Dialyse, CHU Bordeaux, Bordeaux, France. 2 UMR CNRS 5164, CNRS, Bordeaux, France. 3 Department of Nephrology and Organ Transplantation CHU Rangueil, Toulouse, France. 4 Laboratoire d'Immunologie et Immunogénétique, CHU Bordeaux, France. 5 Laboratoire d'Anatomie Pathologique, CHU Bordeaux, France. 6 Department of Immunology, CHU Rangueil, Toulouse, France. 7 INSERM U1043, IFR-BMT, Toulouse, France.
Thomas
T
Bachelet
Charlie
C
Martinez
Arnaud
A
Del Bello
Lionel
L
Couzi
Salima
S
Kejji
Gwendaline
G
Guidicelli
Sébastien
S
Lepreux
Jonathan
J
Visentin
Nicolas
N
Congy-Jolivet
Lionel
L
Rostaing
Jean-Luc
JL
Taupin
Nassim
N
Kamar
Pierre
P
Merville
D000208:Acute Disease; D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D005602:France / Q000453:epidemiology; D006084:Graft Rejection / Q000097:blood / Q000453:epidemiology / Q000276:immunology*; D006085:Graft Survival; D015236:HLA-C Antigens / Q000276:immunology*; D006682:HLA-DP Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007518:Isoantibodies / Q000097:blood*; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D015236:HLA-C Antigens; D006682:HLA-DP Antigens; D007518:Isoantibodies