Flow cytometric crossmatching in primary renal transplant recipients with a negative anti-human globulin enhanced cytotoxicity crossmatch.
Flow cytometric crossmatching (FCXM) and panel reactive antibody (PRA) screening techniques are more sensitive than anti-human globulin enhanced cytotoxicity (AHG-CDC) techniques at detecting anti-HLA antibodies. The clinical significance of a positive FCXM in primary renal transplant recipients with a negative AHG-CDC crossmatch is unclear. We performed retrospective FCXM and flow cytometric panel reactive antibody (FlowPRA) determinations in primary renal transplant recipients with a negative T cell AHG-CDC crossmatch and a negative B cell CDC crossmatch pretransplant. Eighteen (13%) of 143 patients exhibited a positive retrospective T cell FCXM. Of these patients, six (33%) experienced early graft loss with explant histology, demonstrating antibody-mediated rejection in five of six cases. The 12 patients with positive T cell FCXM who maintained their grafts experienced more adverse events posttransplant, including more early, steroid-resistant, and recurrent rejection. Furthermore, in a subgroup of patients undergoing protocol biopsies, those with a positive T cell FCXM exhibited more subclinical rejection. Anti-HLA antibodies were detected by FlowPRA in all 18 patients with a positive T cell FCXM, whereas AHG-CDC PRA detected antibodies in only 8 of 18 patients. Therefore, flow cytometric techniques identify sensitized primary renal transplant recipients undetected by AHG-CDC techniques. In those patients, a positive T cell FCXM is associated with an increased risk of early graft loss due to antibody-mediated rejection and may represent a relative contraindication to transplantation. Moreover, those patients are also at increased risk of severe and recurrent rejection, which may carry implications for long-term graft outcomes.
Karpinski
Martin
M
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Rush
David
D
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Jeffery
John
J
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Exner
Markus
M
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Regele
Heinz
H
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Dancea
Silvia
S
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Pochinco
Denise
D
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Birk
Patricia
P
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
Nickerson
Peter
P
Departments of *Medicine, Pathology, and Pediatrics, University of Manitoba, Winnipeg, Manitoba, Canada; and Departments of Laboratory Medicine and Clinical Pathology, University of Vienna, Austria.
D000328:Adult; D000906:Antibodies / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D005916:Globulins / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology / Q000503:physiopathology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007114:Immunization; D016030:Kidney Transplantation; D008297:Male; D012008:Recurrence; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000906:Antibodies; D005916:Globulins