Tan Jane C, Wadia Persis P, Coram Marc, Grumet F Carl, Kambham Neeraja, Miller Katherine, Pereira Shalini, Vayntrub Tamara, Miklos David B
Department of Medicine, Stanford University Medical Center, Stanford, CA, USA.
Transplantation. 2008 Jul 15;86(1):75-81. doi: 10.1097/TP.0b013e31817352b9.
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.
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.
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).
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.
人类次要组织相容性抗原（mHA）及其相关的临床免疫反应在器官移植中尚未得到充分明确。我们推测接受男性肾脏移植的女性会产生针对Y染色体编码的mHA即H-Y的抗体，并与移植排斥反应相关。
我们检测了118例接受肾脏活检的连续移植受者的血清。通过IgG酶联免疫吸附测定和蛋白质印迹法检测特异性识别重组H-Y抗原RPS4Y1或DDX3Y的抗体。使用针对两种H-Y蛋白的重叠H-Y抗原肽进一步鉴定免疫原性表位。
在26例接受男性肾脏移植的女性受者中，移植后H-Y抗体的产生（1）比其他性别组合更频繁（46%）（P<0.001），（2）与急性排斥反应密切相关（P=0.00048），（3）与活检肾脏中的浆细胞浸润相关（P=0.04），（4）与C4d沉积或供体特异性抗人白细胞抗原（HLA）抗体无关。在两种H-Y抗原中，RPS4Y1更常被识别（P=0.005）。
首次证明了肾脏移植受者中H-Y抗体产生与急性排斥反应之间存在密切关联，这表明在实体器官同种异体移植中，针对明确的mHA的体液免疫反应具有明确的临床相关性，易于监测，并且值得研究其对长期移植功能可能产生的影响。
