Effects of immunoadsorption combined with membrane filtration on complement markers – results of a randomized, controlled, crossover study

Abstract

ClinicalTrials.gov number: NCT01698736. SUMMARYThe complement system has been implicated in several kidney diseases, such as antibody-mediated rejection after kidney transplantation. Antibody-depletion techniques allow successful ABO-and/or HLA-incompatible transplantation. Considering the IgG removal, the use of semi-selective immunoadsorption (IA) has been advocated. However, because of results on incomplete IgM depletion, the adjunctive use of membrane filtration (MF) has been proposed to enhance the removal of macromolecules and to interfere with complement activation. This secondary endpoint analysis of a recently published randomized, controlled, cross-over trial was designed to investigate the effect of combined treatment IA + MF compared to IA alone on complement depletion. Two treatment sequences, a single session of IA + MF followed by IA (and vice versa), were analyzed with regard to C5b-9, properdin, and mannose-binding lectin (MBL) levels. Neither IA alone nor IA + MF provoked complement activation as demonstrated by stable low levels of C5b-9 after the procedure as compared to the previous. The combined treatment substantially lowered properdin (77% vs. 26% reduction, P < 0.0001) as well as MBL concentrations (81% vs. 11% reduction, P < 0.0001). Recovery of properdin and MBL levels appears to be longer after IA alone compared to IA + MF. Depletion of properdin and MBL levels may have potential clinical implications in the setting of kidney transplantation.

Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation

“…IA could be coupled with membrane filtration (Monet ® ). Monet ® filter was used to enhance the removal of molecules possibly involved in the post-transplantation rejection risk such as IgM, C1q, properdin, mannose-binding lectin [8]. It was associated with IA when HLA antibody titer was high (i.e., >12,000).…”

Effect of immunoadsorption alone or combined with membrane filtration on hemostasis parameters

“…Thus, it was shown that IA combined with MF can remove C1q as well as other complement pathway factors, such as properdin and mannose-binding lectin. 14,15 Recently, we have shown that DFPP significantly removes high-molecular-weight proteins from the hemostatic system and decreases levels of protein S (PS) and tissue factor pathway inhibitor (TFPI). 16 In the present study, the aim was to assess whether IA, with or without MF, alters the loss of high-molecular-weight proteins from the hemostatic system.…”

Immunoadsorption Combined with Membrane Filtration to Counteract Early Treatment-Refractory Antibody-Mediated Rejection

“…Besides IgM and C1q, combined apheresis was also shown to interfere with the lectin and the alternative pathway, as elimination of MBL and properdin was enhanced [16]. This finding might strengthen the effect of MF on IgM elimination since it was shown that IgM can directly bind MBL thereby activating the lectin pathway [28].…”

“…We have previously demonstrated in a randomized controlled crossover trial that the combination of nonantigen-specific (i.e., semi-selective) immunoadsorption (IA) together with membrane filtration (MF) allows for efficient elimination of macromolecular effector components such as IgM, C1q, and mannose-binding lectin (MBL) in addition to substantial IgG removal [15,16]. To account for the different pathomechanisms involved in treatment-resistant humoral rejection, we have applied this innovative concept of combined apheresis in a consecutive series of 4 highly sensitized kidney transplant patients with severe early acute C4d+ humoral rejection refractory to standard-of-care treatment with semi-selective IA.…”