Interference of therapeutic antibodies used in desensitization protocols on lymphocytotoxicity crossmatch results.
BACKGROUND
Therapeutic antibodies used to desensitize patients awaiting a human leukocyte antigen (HLA) or ABO-mismatched graft are suspected to interfere with the lymphocytotoxicity crossmatch (LCT-XM) test when they are present in the tested sera because of their potential ability to activate or inhibit the complement.


METHODS
The most frequent therapeutic antibodies (Abs) used in desensitization protocols (intravenous immunoglobulins, rituximab, basiliximab, eculizumab, antithymocyte globulin) were added to a negative- or a positive-control serum at various concentrations, and tested in vitro in a LCT-XM test.


RESULTS
Rituximab turned the LCT-XM positive on B cells at 0.2 μg/mL and antithymocyte globulin turned the LCT-XM positive with T and B cells at 20 μg/mL and 200 μg/mL, respectively. Treatment with dithiothreitol sera, supplemented with rituximab (0.2 and 2 μg/mL) and antithymocyte globulins (20 and 200 μg/mL), partially or totally reduced this positive interference. Intravenous immunoglobulin, eculizumab, and basiliximab did not trigger any interference with the negative control serum. In a positive LCT-XM, eculizumab did not annihilate activation of the rabbit complement. Intravenous immunoglobulins (25 g/L) could partially or totally reduced lysis score of positive crossmatch with weak lysis scores.


CONCLUSIONS
If eculizumab within the serum did not annihilate rabbit complement activation and basiliximab did not interfere with the crossmatch reaction, treatments based on rituximab, antithymocyte globulin and intravenous immunoglobulins need to be taken into account when interpreting a positive or negative crossmatch test.
Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France. Electronic address: davidmilongo@gmail.com.
David
D
Milongo
Laboratoire d'immunologie, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France; Laboratoire d'Immunogénétique Moléculaire, EA 3034, Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: vieu.g@chu-toulouse.fr.
Guillaume
G
Vieu
Laboratoire d'immunologie, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France. Electronic address: sarahblavy@yahoo.fr.
Sarah
S
Blavy
Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France. Electronic address: delbello.a@chu-toulouse.fr.
Arnaud
A
Del Bello
Department of Urology, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France. Electronic address: sallusto.f@chu-toulouse.fr.
Federico
F
Sallusto
Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France; Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: rostaing.l@chu-toulouse.fr.
Lionel
L
Rostaing
Department of Nephrology and Organ Transplantation, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France; Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: kamar.n@chu-toulouse.fr.
Nassim
N
Kamar
Laboratoire d'immunologie, CHU Rangueil, 1 Avenue du Professeur Jean Poulhes, 31059 Toulouse, France; Laboratoire d'Immunogénétique Moléculaire, EA 3034, Université Toulouse III Paul-Sabatier, 118 Route de Narbonne, 31062 Toulouse, France. Electronic address: congy.n@chu-toulouse.fr.
Nicolas
N
Congy-Jolivet
D000017:ABO Blood-Group System / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000920:Antibody-Dependent Cell Cytotoxicity; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D000077552:Basiliximab; D001788:Blood Grouping and Crossmatching / Q000379:methods*; D003167:Complement Activation / Q000187:drug effects; D003951:Diagnostic Errors / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007518:Isoantibodies / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use
D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D011993:Recombinant Fusion Proteins; D000069283:Rituximab; D000077552:Basiliximab; C481642:eculizumab
Desensitization; Drug interference; HLA; Kidney transplantation; Lymphocytotoxicity crossmatch; Therapeutic antibodies