Outcome of Patients with Preformed Donor-Specific Antibodies Following Alemtuzumab Induction and Tacrolimus Monotherapy

Abstract

It has been shown that low-level preformed donorspecific antibodies (DSAbs) detected by luminex beads in the setting of a negative CDC and flow cytometry crossmatch (CDC/FCXM) are associated with inferior allograft outcomes. The relevance of preformed DSAbs in patients receiving alemtuzumab induction and tacrolimus monotherapy has not been studied. Four hundred and eighty renal transplant recipients with a negative CDC/FCXM had their pretransplant sera retrospectively screened for DSAbs. 45/480 (9.4%) of patients were found to have preformed DSAbs. Females and patients receiving regrafts were more likely to have a DSAb (p = 0.008 and p < 0.0001, respectively). Patients with DSAbs had inferior allograft survival (p = 0.047), increased incidence of antibodymediated rejection (p < 0.0001) and inferior allograft function at 6 months posttransplant (p = 0.017). Patients with HLA class I DSAb (alone or in combination with a Class II DSAb) with high mean fluorescence intensities (MFIs) were at highest risk. We conclude that patients with preformed DSAb are at high risk of adverse outcomes when receiving a minimal immunosuppressive regime incorporating alemtuzumab induction. Patients found to have a preformed DSAb despite a negative crossmatch might benefit from augmented immunosuppression.

Donor-Specific Antibodies Adversely Affect Kidney Allograft Outcomes

“…Notably, mean and median age of the patients included with DSA-SPA tended to be similar to the age of their comparative cohort without DSA in each individual study. The types of donors included in these studies varied; two studies included only deceased-donor transplants, 5,10 one study included only living-donor transplants, 8 three studies included both donor types, 7,9,11 and one study did not describe the type of donors in the cohort. 6 Induction and maintenance regimens also varied widely across studies.…”

“…Gupta et al reported that no induction regimen was routinely used, whereas the other studies used antithymocyte globulin, alemtuzumab, or an IL-2 inhibitor (Table 2). [5][6][7][8][9][10][11] Two of the seven studies consistently used a steroid-free maintenance regimen, including Willicombe et al, who maintained patients on tacrolimus monotherapy. 10,11 Patel et al 8 and Verghese et al 9 maintained patients on a calcineurin inhibitor (CNI) and prednisone, whereas the Gupta, Couzi, and Higgins and colleagues used a triple-drug regimen that included a CNI, antimetabolite, and prednisone.…”

“…[5][6][7][8][9][10][11] All seven studies were retrospective cohort studies; three were from the United States and four from Europe. Our ability to compare certain patient characteristics and immunosuppression protocols across studies was limited by the variable reporting of these characteristics in the included reports.…”

HLA Antibody Detection With Solid Phase Assays: Great Expectations or Expectations Too Great?

“…For example, among patients with DSA who were transplanted following desensitization, the association between pretransplant DSA levels >5000 MFI and the likelihood of AMR was quite high (47). In contrast, a study involving Alemtuzumab-induced crossmatch negative recipients where the presence of DSA was determined retrospectively (61). In that study, the pretransplant presence of DSA was strongly associated with the likelihood of experiencing AMR.…”

Clinical Immunosuppression

“…Immunosuppression can be achieved by several mechanisms that affect lymphocytes including lymphocyte depletion, diversion of lymphocyte traffic, or blocking lymphocyte response pathways [14,15].…”