De Novo Development of Antibodies to Cardiac Myosin and Vimentin in Pediatric Heart Transplant Recipients: A Single Center Pilot Study

Abstract

Purpose Pre and post heart transplant (Tx) HLA antibody (ab) surveillance has become routine. Recent studies show a relationship between donor specific HLA abs (DSA), rejection and coronary vasculopathy (CAV). Little is known about the frequency of non HLA abs to cardiac self antigens (myosin, vimentin) in pediatric heart tx recipients. Aim of this pilot study is to characterize the frequency of non HLA abs in a cohort of pediatric heart tx pts and begin to explore their association with clinical events. Methods Residual sera from 30 post tx HLA ab studies from 12 pts were available. Abs to Vimentin (Anti-V) and cardiac myosin (Anti-M) were determined using an ELISA developed in our lab. Positive (pos) values were based upon a standard curve with known concentrations of myosin or vimentin. Values > 300 ng/ml for Vimentin and > 140 ng/ml for myosin were deemed pos which is 2 standard dev from negative sera. Additionally, pre tx samples were available from 10/12 pts for ab analysis. Clinical events: rejection, cav and death were recorded along with HLA ab results from each sample. Results HLA ab sensitization was noted in pre tx sera from 5/12 (PRA 3-64%) children whereas only 1/10 had sensitization to non HLA abs prior to tx. Of the 30 post tx samples, 27 were pos for Anti-V and 28 for Anti-M; while only 7 were pos for DSA. Of those with DSA, 5 had MFI 5K. Clinically, 4 pts had no rejection, 3 had pAMR1i+ only and 5 had CR ≥ 2R and/or pAMR 2 or 3. Three pts developed CAV, two of whom died. Anti-V and Anti-M abs had a moderate correlation (R=0.649) with each other and there was a trend toward higher levels of Anti-V over time in pts with CAV and death. Table 1 includes summary data on all 12 pts; Anti-V and Anti-M ab levels are shown in tertiles. Conclusion De novo Anti-V and Anti-M abs are common post pediatric heart tx and not related to DSA. These abs may be implicated as contributing factors to detrimental clinical events post tx. The significance and prevalence of these abs post heart tx warrant further study.