Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation

Abstract

Introduction Donor specific anti-HLA antibodies (DSA) are common following heart transplantation and are associated with rejection, cardiac allograft vasculopathy (CAV), and mortality. Currently a non-invasive diagnostic test for pathologic AMR (pAMR) does not exist. Methods 221 consecutive adult patients underwent heart transplantation from January 1st, 2010 through August 31th, 2013 and followed through October 1st, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included the association of DSA (stratified by MHC Class and de-novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of CAV. Results During the study period 69 individual patients (31.2%) had DSA (24% had de-novo DSA) and there were 74 episodes of pAMR in 38 unique patients. The sensitivity of DSA at any MFI to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (OR 5.37, 95% CI 1.34–21.47, p=0.018), adjusting for age, gender, and timing of AMR. Circulating Class II DSA after transplantation increased the risk of future pAMR (HR 2.97, 95% CI 1.31–6.73, p=0.009). Patients who developed de-novo Class II DSA had a 151% increase in risk of graft loss (contingent on 30-day survival) compared with those who did not have DSA (95% CI 1.11–5.69, p=0.027). Conclusions DSA were inadequate to diagnose pAMR, but Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss.

The role of C4d deposition in the diagnosis of antibody-mediated rejection after lung transplantation

“…However, it is noteworthy that only a minority of patients cleared all DSA in spite of aggressive antibody-depleting therapy. Furthermore, the prevalence of DSA to class II HLA, and to HLA-DQ in particular, in our cohort is consistent with previous studies in pulmonary, renal, and cardiac AMR (2, 3, 5, 28–33). Emerging data suggest that HLA-DQ may be uniquely immunogenic (34).…”

Early immune biomarkers and intermediate-term outcomes after heart transplantation: Results of Clinical Trials in Organ Transplantation-18

“…19,20 In an unselected contemporary heart transplant population, however, outcomes appear to have improved even in al- F I G U R E 4 Change in percent atheroma volume between baseline and month 12 in subjects who did not and who did meet the composite endpoint, the endpoint of death, and retransplantation and the endpoint of stent, myocardial infarction, or CAV diagnosis after 12 months seemed to be associated with less risk of CAV in the long-term in the CTOT-18 study. However, intermediate-term outcomes were similar in subjects with and without anti-HLA antibody.…”

Coronary artery disease in heart transplantation: new concepts for an old disease

“…More recently, DSA and manifestations of AMR have been extensively investigated as measurable markers of the immune activation against vascular alloantigens. In our review, we found that eleven of twelve studies supported DSA/AMR involvement with CAV development [], with the only neutral study likely underpowered by the very small sample size. Anti‐HLA DSA class II and combination of class I and class II were found associated with angiographic CAV , while non‐DSA HLA antibodies did not appear to bear meaningful risk .…”