Isoagglutinin‐reduced immunoglobulin retains efficacy in mouse models of immune thrombocytopenia and rheumatoid arthritis and is less likely to cause intravenous immunoglobulin–associated hemolysis

BACKGROUND: Immunoglobulin therapy including intravenous immunoglobulin (IVIg) has been used as an effective treatment for autoimmune/inflammatory conditions with few side effects. However, high‐dose IVIg (1‐2 g/kg) has been recognized as a cause of hemolytic anemia in non–blood group O patients. Hemolysis when observed has been due to anti‐A/anti‐B isoagglutinins contained in the IVIg. Recently, an isoagglutinin‐reduced IVIg, whereby the anti‐A and anti‐B titers have been reduced by immunoaffinity chromatography, has been introduced; however, whether this new product is as efficacious as nonreduced immunoglobulin (Ig) or will result in less IVIg‐associated hemolysis has not been resolved. STUDY DESIGN AND METHODS: We used in vitro phagocytosis by monocytes and proinflammatory/anti‐inflammatory macrophages, with isoagglutinin‐reduced and ‐nonreduced Ig opsonized group A(1), B, and A(1)B red blood cells, to estimate clinical significance of the IgG isoagglutinins. We also used immune thrombocytopenia (ITP) and rheumatoid arthritis (RA) mouse models to examine the in vivo efficacy of isoagglutinin‐reduced versus ‐nonreduced Ig on the amelioration of the diseases. RESULTS: In contrast to nonreduced Ig, phagocytosis was largely absent when isoagglutinin‐reduced Ig was used at a concentration equivalent to a patient receiving 2 g/kg. The in vivo efficacy of isoagglutinin‐reduced versus nonreduced Ig on the amelioration of experimental ITP and RA was similar, indicating no loss of efficacy due to the chromatographic removal of isoagglutinins. CONCLUSION: Isoagglutinin‐reduced Ig should have efficacy similar to nonreduced Ig and result in less IVIg‐associated hemolysis.