Changes of Circulating Antibody Levels Induced by ABO Antibody Adsorption for ABO-Incompatible Kidney Transplantation

Abstract

ABO-incompatible kidney transplantation using immunoadsorption to remove anti-A/B antibodies has become a successful clinical practice. Since the data on the specificity of the ABO columns are controversial, the present study assessed the efficiency and specificity of the ABO immunoadsorption, the effect on total immunoglobulins and antibodies previously induced by vaccination. Anti-A/B antibodies were measured by agglutination and ABO flow cytometry, total IgG/IgM, carbohydrate-and protein-specific antibodies by nephelometry and ELISA. The first immunoadsorption not only efficiently reduced donor-specific anti-A/B IgM (81%) and IgG (56%) but also reduced compatible anti-A/B IgM (59%) and IgG (34%). The measurements of antidonor A/B antibodies by direct agglutination (IgM) or flow cytometry better represented the effective antibody levels than the indirect agglutination test (IgG). The median reduction of total IgM and total IgG levels after a single immunoadsorption was 34% and 18%, respectively. Antibodies against pneumococcus and haemophilus polysaccharide antigens were significantly reduced, whereas antitetanus and antidiphtheria protein antibodies were not affected. Intravenous immunoglobulin administration restored the protective anticarbohydrate antibody levels. In summary, immunoadsorption efficiently removed antidonor A/B antibodies, but was not specific for A/B antigens. Anti-A/B antibody levels as determined by ABO flow cytometry are useful to establish the minimal number of immunoadsorptions needed for successful ABO-incompatible transplantation.Key words: ABO blood group, ABO incompatible kidney transplantation, flow cytometry, immunoadsorption AbbreviationsABOi, ABO-incompatible; a Gal, Gala 1-3Gal antigen; DAT, direct agglutination test; IA, immunoadsorption; IAT, indirect antiglobulin tests; IVIG, intravenous immunoglobulin; MFIR, geometric mean fluorescence intensity ratio; RBC, red blood cell.

Immunadsorption und Plasmapherese bei Glomerulonephritiden und Nierentransplantation – Wird die Immunadsorption die Plasmapherese ersetzen?

“…Die Antikörperelimination erfolgt mittels antigenspezifischer IA unter Verwendung der Glycosorb ® -AB0-Säule (Glycorex Transplantation, Lund, Schweden). Bei der Glycosorb ® -AB0-Säule handelt es sich um eine Einmalsäule, die effektiv spenderspezifische Anti-A-oder Anti-B-IgG-und -IgM-Blutgruppenantikörper mit einer Absenkrate von 56 beziehungsweise 81 % während der ersten Behandlung eliminiert [10]. Das sowohl für die Desensibilisierung bei Blutgruppeninkompatibilität als auch zur Elimination von HLA-Antikörpern eingesetzt werden kann ("Onesize-fits-all"-Protokoll, Abb.…”

Characteristics, Detection, and Clinical Relevance of Alloantibodies in Kidney Transplantation

“…A1 and A2 blood group antigens differ qualitatively and quantitatively (see above). Indeed, for transplantation from A2 donors into B or O recipients, anti-A1 IgG titers that were above 1:128 have been shown to represent a significant risk factor for AMR (Squifflet et al, 2004;Tyden et al, 2010;Valli et al, 2009;Warren et al, 2004). In addition, Alkhunaizi reports that up to 8% of A2 individuals have anti-A1 IgG antibodies in their sera (Alkhunaizi, 2006).…”

“…For example, the A blood group antigen has higher expression levels than the B blood group antigen. Interestingly, immunohistochemical analysis has revealed that the A2 blood group has the lowest cell surface expression (Pober et al, 1997;Shimmura et al, 2004;Yung et al, 2007); however, data analysis of kidney transplants that has been performed across ABO barriers has not revealed statistically significant differences between the A (donor) →B (recipient) or B (donor) →A (recipient) groups (Squifflet et al, 2004;Sugiyama et al, 2005;Valli et al, 2009). …”

“…In this method, immunoabsorption columns that were filled with A/B oligosaccharides (Glycosorb, Glycorex Transplantation AB, Lund, Sweden) were used instead of PP in order to remove anti-A or anti-B antibodies. In addition, Rituximab was used instead of splenectomy in order to prevent rebound effects (Tyden 2007;Valli et al, 2009). These investigators demonstrated that anti-AB IgG antibody titers were reduced from 1:2 -1:128 to 1:1-1:2 after 4-8 cycles of immunoabsorption.…”

ABO-Incompatible Kidney Transplantation

“…In contrast to plasmapheresis, immunoadsorption method can selectively remove anti-ABO antibodies, unaffecting the levels of the other plasma proteins. The blood type-specific columns can effectively remove anti-A or anti-B antibodies, and approximately 30% of anti-A/B IgM and 20% of anti-A/B IgG levels can be removed after a single treatment (Valli et al, 2009). In spite of its physiologic technique and successful clinical applications, the high cost of immunoadsorption column is a major limiting factor blocking its widespread use.…”