Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels.
BACKGROUND
Transplant glomerulopathy (TG) is a histopathologic entity of kidney allografts related to anti-human leukocyte antigen (HLA) antibodies. The goal of this study was to determine the relationships among antibody characteristics (level and specificity), risk for TG, and graft survival.


METHODS
The presence and characteristics of anti-HLA antibody were assessed by single antigen beads assays in stored pretransplant sera from 598 kidney recipients with negative T-cell crossmatch. Transplant glomerulopathy was diagnosed by surveillance and clinical biopsies.


RESULTS
Thirty-nine percent of patients presented with anti-HLA antibodies pretransplant. Transplant glomerulopathy was diagnosed in 73 patients (12%) during 54+/-19 months of follow-up. The risk of TG increased with higher anti-HLA-II antibody levels (HR=1.890, 95% CI 1.42-2.52; P<0.0001), donor specificity of the antibodies (3.524 [1.67-7.44]; P=0.001), and in patients with history of antibody-mediated rejection (4.985 [2.77-8.97]; P<0.0001, multivariate Cox). Graft survival during the follow-up period was 95% without TG and 62% with TG (P<0.0001). The presence of C4d in peritubular capillaries was an independent risk factor for graft failure after TG diagnosis. Thus, 25% of TG/C4d and 80% of TG/C4d+ grafts failed (P<0.0001). Of interest, higher anti-HLA-II levels were related to the presence of C4d (3.216 [1.376-7.517]; P=0.007).


CONCLUSIONS
In T-cell negative crossmatch patients, higher anti-HLA-II antibody levels are related to the increase in the risk of developing TG. Higher antibody levels are also related to the presence of C4d in peritubular capillaries in TG biopsies. Furthermore, the presence of C4d in TG is related to the reduced graft survival.
Issa
Naim
N
Division of Nephrology and Hypertension and Transplant Center, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Cosio
Fernando G
FG
Gloor
James M
JM
Sethi
Sanjeev
S
Dean
Patrick G
PG
Moore
S Breanndan
SB
DeGoey
Steve
S
Stegall
Mark D
MD
D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous / Q000276:immunology
D001323:Autoantibodies; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II