Anti-idiotypic antibodies from highly sensitized patients stimulate B cells to produce anti-HLA antibodies.
BACKGROUND
Sustained allosensitization increases waiting time for transplantation and increases the risk of rejection. The purpose of this study is to examine the effect of anti-idiotypic antibodies on B-cell responses and to define their role in alloantibody production.


METHODS
The Immunoglobulin G (IgG) fraction, or the sera of 19 highly sensitized (HS) patients was absorbed to remove anticlass I antibody and was incubated with B cells. The culture supernatant was assayed for antihistocompatibility leukocyte antigen (HLA) antibody and tested for reactivity against a panel of normal lymphocytes. Similar studies were performed in 5 of the 19 patients who had a fall in alloantibody levels.


RESULTS
The IgG (HS) fraction induced anti-HLA antibody from normal and autologous B cells in all 19 HS patients studied. The reactivity to HLA antigens in the culture supernatant was similar to the sera for each patient studied. The in vitro generated anti-HLA antibody bound to the IgG fraction used to stimulate the B cells. The in vitro production of anti-HLA antibodies was absent in the serum of all five patients who became nonsensitized.


CONCLUSIONS
All patients who have high levels of alloantibody have anti-idiotypic antibodies in their sera that stimulate B cells to produce anti-HLA class I antibody similar in reactivity to that of their own sera. In the patients who have nondetectable alloantibodies in their sera, the stimulating anti-idiotypes are not measurable. Anti-idiotypic antibodies may act as a vaccine and cause sustained levels of alloantibody production.
Toronto Western Hospitals, University Health Network, Toronto, Ontario, Canada.
Nashrudeen
N
Hack
Sarita
S
Angra
Eva
E
Friedman
Theresa
T
McKnight
Carl J
CJ
Cardella
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007518:Isoantibodies / Q000096:biosynthesis*; D008297:Male
D000888:Antibodies, Anti-Idiotypic; D006680:HLA Antigens; D007074:Immunoglobulin G; D007518:Isoantibodies