Anti-gal A/B, a novel anti-blood group antibody identified in recipients of abo-incompatible kidney allografts.
BACKGROUND
The most prevalent anticarbohydrate antibodies in human serum are anti-Gal interacting specifically with the alpha-gal epitope (Galalpha1-3Galbeta1-4GlcNAc-R) and anti-blood group antibodies interacting with blood group A and B antigens. The alpha-gal epitope, although absent in humans, comprises part of the core of carbohydrate chain in A and B antigens. Therefore, it was of interest to determine whether immunoglobulin (Ig) G antibodies, elicited in patients rejecting ABO-incompatible kidney allografts, can interact with the alpha-gal epitope.


METHODS
Anti-A and anti-B antibodies were determined by enzyme-linked immunosorbent assay (ELISA) with blood group A or B human red cell membranes, as solid phase antigens. Anti-Gal was determined by ELISA with alpha-gal-bovine serum albumin as solid-phase antigen. Specific removal of anti-Gal was performed by adsorption on fixed rabbit red cells.


RESULTS
Blood group O patients who underwent transplantation with either A or B kidney produced an antibody that bound to all three carbohydrate antigens. This multispecific antibody, designated anti-Gal A/B, is specific to the core alpha-gal epitope within A and B antigens. Recipients of allograft expressing incompatible blood group B also produce anti-Gal B antibody, which binds to the core alpha-gal epitope only in the B antigen. Anti-Gal A/B and anti-Gal B constitute most of the elicited anti-blood group antibody response. Allograft recipients also produced pure anti-A, or pure anti-B, which require the complete blood group structure for binding.


CONCLUSIONS
The findings in this study imply that much of the immune response elicited by incompatible A or B antigens on kidney allografts results in activation of anti-Gal B-cell clones producing antibodies to the core alpha-gal epitope in these blood group antigens. Only less than 25% of the elicited antibodies interact with the complete A or B antigens (i.e., pure anti-A or pure anti-B). These findings suggest that prevention of the anti-Gal response may decrease the immune rejection of ABO-incompatible allografts.
Galili
Uri
U
Department of Cardiovascular-Thoracic Surgery, Rush University, Chicago, IL 60612, USA. uri_galili@rush.edu.
Ishida
Hideki
H
Tanabe
Kazunari
K
Toma
Hiroshi
H
D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000917:Antibody Formation; D000939:Epitopes / Q000276:immunology; D006596:Hexosaminidases / Q000276:immunology*; D006648:Histocompatibility; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D007518:Isoantibodies / Q000032:analysis*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D000519:alpha-Galactosidase / Q000276:immunology*; D048809:alpha-N-Acetylgalactosaminidase
D000017:ABO Blood-Group System; D000939:Epitopes; D007074:Immunoglobulin G; D007518:Isoantibodies; D006596:Hexosaminidases; D000519:alpha-Galactosidase; C482722:NAGA protein, human; D048809:alpha-N-Acetylgalactosaminidase