Different responses of human anti-HLA and anti-alpha gal antibody to long-term intravenous immunoglobulin therapy

Concentrated human immunoglobulin (IVIG) has been administered intravenousl y in the treatment of autoimmune disorders and to reduce anti-HLA antibodie s in highly sensitized patients awaiting organ transplantation. It has also been shown, in experimental animals, to prevent the hyperacute rejection o f discordant xenografts, possibly by anticomplement activity. The aim of th e present study was to assess the effect of IVIG therapy on both acquired a nti-HLA antibodies and natural antigalactose alpha 1-3 galactose (alpha Gal ) antibodies in five patients awaiting heart transplantation. Five patients placed on mechanical circulatory support who had developed high HLA panel- reactive antibodies (PRA) or in whom the percentage of PRA was increasing r apidly were treated weekly with 500 mg/kg IVIG, which contained 1% of anti- alpha Gal IgG. Levels of PRA, anti-alpha Gal IgG and IgM, and serum cytotox icity to pig cells were measured before, during, and after therapy. PRA per centages in the five patients were initially 85%, 53%, 23%, 19% and 19% (me an 39%). Mean PRA fell by 66% after 3 months of therapy (to a mean PRA of 1 4%), and by 96% after 6 months therapy (to a mean PRA of 2%), Anti-alpha Ga l antibody levels and serum cytotoxicity to pig aortic endothelial cells di d not change significantly. These results confirm the effectiveness of IVIG therapy in reducing PRA in HLA highly sensitized patients. It is likely th at IVIG does not contain the relevant anti-HLA antibody, resulting in an ac celerated catabolism of native alloantibodies. However, as IVIG contains a normal level of anti-alpha Gal IgG, catabolism of anti-alpha Gal IgG is not modified, as it is being continuously replaced. To achieve a decrease in t he anti-alpha Gal IgG level it would be necessary to use IVIG depleted of t his antibody.