ABO Antibody and Complement Depletion By Immunoadsorption Combined With Membrane Filtration - A Randomized Controlled Crossover Trial.

Abstract

Potent antibody depletion techniques have paved the way to successful ABO-incompatible transplantation. Considering its efficiency regarding IgG removal, the use of non-antigen-specific semiselective immunoadsorption (IA) has been advocated. One attractive strategy to overcome the caveat of incomplete IgM depletion and to interfere with complement activation could be the adjunctive use of membrane filtration (MF) to enhance the removal of macromolecules. To investigate the depletion efficiency of semiselective IA plus MF, we conducted a randomized crossover trial including 14 patients treated for autoimmune disease. Two treatment sequences, a single session of IA plus MF followed by IA alone after ≥7 days (and vice versa), were analyzed. IA plus MF markedly enhanced the median percent reduction of ABO-specific IgM as determined by flow cytometry (59% versus 23%, P<0.001) and hemagglutination (2 versus 1 titer steps, P<0.001). Combined treatment also substantially lowered C1q concentrations (86% versus 58% reduction, P<0.001) and the functionality of classical complement as reflected by impaired in vitro C3 activation capability. IgG was strongly reduced without any additional effect of MF. In conclusion, we demonstrate enhanced antibody elimination by adding MF to IA. This and the observed impact on classical complement could markedly enhance the efficiency of apheresis in ABO- and/or HLA-incompatible transplantation. DISCLOSURES:Boehmig, G.: Grant/Research Support, Unrestricted grant.