H-Y antibody development associates with acute rejection in female patients with male kidney transplants.
BACKGROUND
Human minor histocompatibility antigens (mHA) and clinically relevant immune responses to them have not been well defined in organ transplantation. We hypothesized that women with male kidney transplants would develop antibodies against H-Y, the mHA encoded on the Y-chromosome, in association with graft rejection.


METHODS
We tested sera from 118 consecutive transplant recipients with kidney biopsies. Antibodies that specifically recognized the recombinant H-Y antigens RPS4Y1 or DDX3Y were detected by IgG enzyme-linked immunosorbent assay and western blotting. Immunogenic epitopes were further identified using overlapping H-Y antigen peptides for both the H-Y proteins.


RESULTS
In the 26 female recipients of male kidneys, H-Y antibody development posttransplant (1) was more frequent (46%) than in other gender combinations (P<0.001), (2) showed strong correlation with acute rejection (P=0.00048), (3) correlated with plasma cell infiltrates in biopsied kidneys (P=0.04), and (4) did not correlate with C4d deposition or donor-specific anti-human leukocyte antigen (HLA) antibodies. Of the two H-Y antigens, RPS4Y1 was more frequently recognized (P=0.005).


CONCLUSIONS
This first demonstration of a strong association between H-Y antibody development and acute rejection in kidney transplant recipients shows that in solid organ allografts, humoral immune responses against well defined mHA have clear clinical correlates, can be easily monitored, and warrant study for possible effects on long-term graft function.
Tan
Jane C
JC
Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.
Wadia
Persis P
PP
Coram
Marc
M
Grumet
F Carl
FC
Kambham
Neeraja
N
Miller
Katherine
K
Pereira
Shalini
S
Vayntrub
Tamara
T
Miklos
David B
DB
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000918:Antibody Specificity; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D012737:Sex Factors; D014019:Tissue Donors
C051256:H-Y antibody; D007518:Isoantibodies