Abstract 13267: Circulating Anti-Intercalated-Disk Autoantibodies are Non-Invasive Markers of High Cellular Rejection Burden in Heart Transplantation
Objective: Serum anti-heart (AHA) and anti-intercalated-disk (AIDA) autoantibodies are markers of autoimmune myocardial disease prior to heart transplantation (HTx). Autoimmune response may occur after solid organ transplantation in association with acute rejection (AR). We assessed the hypothesis that AHA and AIDA may be noninvasive markers of acute AR after HTx.
Methods. We studied 63 stable HTx patients (47 male, aged 52±14 years at HTx, at 100±72 months post-HTx). Serum at last follow-up was assessed for AHA and AIDA by indirect immunofluorescence on cryostat sections of normal O blood group human myocardium and skeletal muscle, blindly from clinical features. Control groups included patients with non-inflammatory cardiac disease (NICD) (n=160, 80 male, aged 37±17), ischemic heart failure (IHF) (n=141, 131 male, age 51±12) and normal blood donors (NBD) (n=270, 123 male, aged 35±11). A rejection score was assigned based on the ISHLT grading on follow-up endomyocardial biopsy as follows:1A=1, 1B=2; 2=3; 3A=4; 3B=5; 4=6. The following scores were calculated for each patient and normalised for the number of biopsies: RS in the total follow-up (TRS); RS in the 1st year (RS 1yr); TRS including only severe grades (greater = 3A) (sev TRS); 1styr RS including only severe grades (sev RS 1yr). Cumulative doses (mg/kg) of Cyclosporin A (CsA), Azathioprine (Aza), steroids at 3, 6, 12 months were also calculated.
Results. The frequencies of AHA and AIDA were higher in HTx (33%; 13%) than in NICD (1%, p=0.0001; 4%, p=0.02), IHF (1%, p=0.0001; 2%, p=0.005) or NBD (2.5% p=0.0001; 0%, p=0.0001 respectively). Positive AHA or AIDA status was not associated with age at HTx, gender, pre-HTx diagnosis, time from HTx. Conversely, AIDA positive patients had higher sev TRS compared to those who were AIDA negative (1.2±0.1 vs. 0.56±0.4, p=0.03), higher (mg/kg) Aza loads at 3 (216±20 vs 123±20, p=0.02), at 6 months (424±17 vs 231± 29, P=0.004) and tended to have higher Aza (818± 89 vs 473± 90) and CsA (2642±1099 vs 1813±235) loads at 12 months (P=0.05).
Conclusion. The finding of AIDA provides a non-invasive predictor of high acute cellular rejection burden after heart transplantation.
- Transplantation/medical aspects
- Immunosuppressive therapy
- Immunologic factors
- © 2011 by American Heart Association, Inc.