Anti-HLA Donor-Specific Antibodies Detected in Positive B-Cell Crossmatches by Luminex® Predict Late Graft Loss

Abstract

The significance of B-cell crossmatching in kidney transplantation is controversial. Recipients (n = 471) transplanted in a single centre from 1987 to 2005 with complete T- and B-cell crossmatch records were studied. Sera from 83 patients transplanted across a positive B-cell crossmatch, with concomitant negative T-cell crossmatch (T-B+) on either current and/or peak sera were studied using Luminex to determine presence of donor-specific antibodies (DSA). Clinical outcomes of T-B+ patients were compared with 386 T-B- patients. T-B+ predicted vascular (p = 0.01), but not cellular (p = 0.82) or glomerular (p = 0.14) rejection. IgG HLA DSA were found in 33% (n = 27) of the T-B+ patients and were associated with higher risk of any (p = 0.047), vascular (p = 0.01) or glomerular (p < 0.001) rejection at 6 months. Of 27 patients with DSA, 18/21 (86%) were the complement-fixing IgG(1) and/or IgG(3) subclass antibodies. DSA imposed a statistically significant higher risk of graft loss 5 years posttransplant (1.8 [1.0-3.3], p = 0.045). This study showed that only one-third of positive B-cell crossmatch (BXM) was caused by DSA and was associated with late graft loss. Thus, using BXM to preclude kidney transplantation may potentially disadvantage >60% of patients in whom BXM is not indicative of the presence of DSA.

Utility of HLA Antibody Testing in Kidney Transplantation

“…80,88,89 AMR rates of 20%-55% are reported under these circumstances, 22,23,83,88,90,91 with AMR negatively affecting the impact of DSA on graft survival in some studies 90 but not all. 83 In series where DSA are associated with worse allograft survival, 82,83,88,[92][93][94][95] DSA MFI is an imperfect discriminator of outcomes. In contrast, other groups identified no change in rejection or graft survival in patients who were DSA positive but XM negative.…”

Cross-matches in Transplantation: Each is Complementary to Other

“…Positive B cell crossmatch correlates significantly only when simultaneously class II DSA is also detected by luminex technology. 39 Positive T cell crossmatch in the setting of negative B cell crossmatch is usually considered as technical error. 40 …”

Pre-transplant low level HLA antibody shows a composite poor outcome in long-term outcome of renal transplant recipients

“…Since that time a large body of evidence has been accumulated documenting the importance of antibody in organ transplantation. [17][18][19] An important factor affecting long-term graft survival of graft is the development of allograft nephropathy. This disease is considered to be a major cause of long-term renal allograft dysfunction, and a variety of immune and non-immune processes can contribute to its development.…”