Serial assessment of early antibody binding to decellularized valved allografts

Abstract

ObjectivesDecellularized homograft valves (DHV) appear to elicit an immune response despite efficient donor cell removal.Materials and methodsA semiquantitative Dot-Blot analysis for preformed and new recipient antibodies was carried out in 20 patients following DHV implantation on days 0, 1, 7, and 28 using secondary antihuman antibodies. Immune reactions were tested against the implanted DHV as well as against the stored samples of 5 non-implanted decellularized aortic (DAH) and 6 pulmonary homografts (DPH).ResultsIn this study, 20 patients (3 female and 17 male patients) were prospectively included, with a median age of 18 years and an IQR of 12–30 years. Six patients received DPH and 14 received DAH. The amount of antibody binding, averaged for all patients, decreased on post-operative days 1 and 7 compared to pre-operative values; and on day 28, antibody binding reached close to pre-operative levels (16.8 ± 2.5 on day 0, 3.7 ± 1.9 on day 1, 2.3 ± 2.7 on day 7, and 13.2 ± 3.7 on day 28). In comparison with the results in healthy controls, there was a higher amount of antibody binding to DAH than to DPH. The mean number of arbitrary units was 18.4 ± 3.1 in aortic and 12.9 ± 4.5 in pulmonary DHV (p = 0.140). Male patients exhibited higher antibody binding to aortic DHV than female patients (19.5 ± 2.1 vs. 1.6 ± 6.7). The p-value calculation was limited, as only two female patients received DAH. There was no correlation between the amount of overall antibody binding to DHV with respect to donor age (Kruskal–Wallis test p = 0.550). DHV recipients with a sex mismatch to the donor showed significantly less antibody binding (6.5 ± 1.8 vs. 13.7 ± 1.8; p = 0.003). Our main finding was an increase in antibody binding in younger patients receiving decellularized aortic allografts. This increase was higher in patients with early degeneration signs but was not specific to the individual DHV implanted nor previous DHV implantation. Antibody binding toward explanted DHV was significantly increased in implicating antibody-mediated DHV degeneration.ConclusionSerial assessment of tissue-specific antibody binding revealed an increase in some patients within 4 weeks after surgery, who subsequently developed early signs of allograft degeneration. Further studies with larger sample sizes are needed to confirm the prognostic relevance of increased antibody activity in addition to targeted research efforts to identify the molecular agents triggering this type of antibody response.

Five-year results from a prospective, single-arm European trial on decellularized allografts for aortic valve replacement—the ARISE Study and ARISE Registry Data

“…3 show DAH results in young adults in comparison to the conventional alternatives of mechanical valves, the Ross procedure and standard bioprostheses. Other data were taken from recent large-scale meta-analyses from Takkenberg et al [ 2 , 5 , 16 ]. Ross results include right ventricular procedures.…”

“…To date, there is no information available about which exact antigene induces the immune response in DAH. We have shown highly individual humoral responses towards decellularized tissue in vitro and have initiated prospective serial assessment in vivo following implantation of decellularized aortic and pulmonary homografts [ 15 , 16 ]. Current hypotheses point towards so-called matrikines, specific peptides of the extracellular matrix that may result from the decellularization process as a target for the host immune system [ 21 ].…”

“…The near-normal haemodynamics in combination with the ability to repair a malfunctioning aortic root are especially important for patients with impaired myocardial function and patients with multiple previous aortic valve procedures [ 14 ]. Recent studies, however, suggested that an immunological, antibody-mediated response is present in almost all patients, which appears to be highly individual in terms of intensity [ 15 , 16 ].…”

Paediatric aortic valve replacement using decellularized allografts: a multicentre update following 143 implantations and five-year mean follow-up

“…Despite thorough decellularization and detailed quality assurance through individual DAH testing before release, DAH appear to elicit a low-grade immune response, which, in contrast to classic T-cell mediated immune reactions, is thought to be more antibody-mediated [ 18 ]. We have shown the highly individual antibody binding towards specific decellularized homografts and are currently performing longitudinal analyses on humoral immune responses in patients following DAH implantation [ 13 , 19 ]. To date, no information is available on the potential antigen(s) causing these immunologic response.…”

Aortic Valve Replacement in Adult Patients with Decellularized Homografts: A Single-Center Experience

“…This is of utmost importance for patients who may later require organ transplantation [49]. Some patients, especially pediatric ones, with signs of early degeneration of decellularized homografts, seem to experience an immune response despite efficient donor cell removal [50,51]. Nonetheless, decellularized homografts in pediatric and very young adults demonstrate a significantly higher freedom from SVD and endocarditis 10 years following intervention compared to bovine jugular vein conduits [52].…”