Abstract
Unlike in other solid organ transplantations, the role of pre-existing antibodies to HLA in liver transplant is not well defined. The presence of alloantibody in liver transplantation has been thought to have no severe deleterious impact on grafts survival, therefore crossmatchings is not routinely performed prior to liver transplantations. Recent reports suggest a correlation between positive donor specific antibody (DSA) and adverse graft outcome leading to reassessment of these views. Detection of DSA by current solid phase immunoassays is highly sensitive and specific. The correlation between DSA detected by immunoassays and their relevance in flow cytometric crossmatch (FCXM), C1q testing and subsequent liver transplantation has not been analyzed.
We retrospectively examined the predictive value of detection of DSA by FCXM or C1q binding ability of the DSA from 175 liver transplant recipients. LABScreen Single Antigen (SAB) immunoassay revealed anti-HLA in 44 of 175 patients. These positive serum were tested by FCXM and C1q assays.
In SAB positive patients, the sensitivity of FCXM in detecting DSA is 67% and the negative predictive value is 90.5%, whereas C1q tests revealed all DSAs identified by SAB were complement fixing. Two of the four patients with positive DSA detected by all three tests developed biopsy proven acute/subacute immune mediated (plasma cell) rejection. Two patients with positive DSA by C1q but negative by FCXM did not develop rejection over 8-month follow up period.
These data suggest DSA resulting in FCXM positivity can lead to liver allograft dysfunction, however clinical relevance of C1q assay liver transplantation is still uncertain given none of patients with positive C1q DSA and negative FCXM have developed rejection.