Chimerism in peripheral blood of sensitized patients waiting for renal transplantation: clinical implications.
BACKGROUND
Potential renal transplant recipients with preformed antibodies to HLA resulting from previous transplants, pregnancy, and/or transfusions are unlikely to receive an allograft. The factors contributing to the long-term maintenance of antibody titers in these individuals are still unknown. In the present study, we sought to determine whether chimerism in the blood correlates with maintenance of HLA sensitization in highly sensitized patients.


METHODS
Qualitative analysis of chimerism in blood of sensitized patients was assessed by polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) to HLA-DR. PCR single-strand conformation polymorphism (PCR-SSCP) was used to confirm the extra HLA-DR antigens detected by PCR-SSOP.


RESULTS
Fourteen of 36 patients (38.9%) were positive for more than two HLA-DR indicative of chimerism. The presence of extra HLA-DR was confirmed by PCR-SSCP. When patients were analyzed on the basis of their panel-reactive antibody (PRA) status, 10 of 15 (66.7%) were positive for chimerism in the sensitized group, compared with only two of eight (25%) in the unsensitized group. Of the five males in the sensitized group who had received a blood transfusion but not a transplant, three were positive for chimerism. An association was observed between chimerism and maintenance of sensitization. None of the eight normal subjects studied demonstrated chimerism.


CONCLUSIONS
The results obtained with sensitized patients suggest an association between blood chimerism and maintenance of HLA sensitization. We speculate that chimerism may lead to long-term maintenance of anti-HLA antibody titers. This finding implies that abolition of chimerism could result in the eventual elimination of antigenic stimuli for antibody production against HLA antigens.
SivaSai
K S
KS
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Jendrisak
M
M
Duffy
B F
BF
Phelan
D
D
Ravenscraft
M
M
Howard
T
T
Mohanakumar
T
T
D000906:Antibodies / Q000276:immunology; D005260:Female; D006684:HLA-DR Antigens / Q000097:blood; D006650:Histocompatibility Testing; D006801:Humans; D007114:Immunization; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D018183:Transplantation Chimera; D019172:Transplantation Conditioning
D000906:Antibodies; D006684:HLA-DR Antigens; D015345:Oligonucleotide Probes