Monitoring of two intravenous immunoglobulin preparations for immunoglobulin G subclasses and specific antibodies to bacterial surface antigens and relation with their levels in treated immunodeficient patients

Abstract

Patients with antibody deficiency disorders are highly susceptible to bacterial infections. Replacement therapy with intravenous immunoglobulin preparations (IVIG) has been established in such patients for two decades. The efficacy of IVIG treatment depends on the amount of functional pathogen-specific antibodies provided. The present study was undertaken to determine the levels of immunoglobulin classes, IgG subclasses, and specific antibodies to bacterial surface antigens in two different IVIG preparations (Sandoglobulin® and Gamimmune®) and blood sera of IVIG-treated immunodeficient patients. The levels of IgG, IgA, IgM and IgG subclasses were determined in both IVIG preparations and in patients’ sera and were compared with those of healthy individuals. Sandoglobulin® contained significantly higher concentrations of IgA, IgG 2 and IgG 4 than Gamimmune®. The latter contained higher concentrations of IgG 1. Patients treated with Gamimmune® had significantly lower concentration of IgG 4 as compared with healthy individuals and Sandoglobulin®-treated patients. This finding was related to the preparation’s composition. Screening of 20 lots from each preparation for antibodies to frequent clinically isolated strains of Escherichia coli, Staphylococcus aureus, S. epidermidis, Klebsiella pneumoniae and Enterococci spp. showed a high lot-to-lot variability. In order to overcome the lot-to-lot variability and correlate the observed effects with each IVIG preparation, the administered IVIG lots were selected so that their titers were in the interval of mean value±S.D. for each pathogen. The two tested preparations showed significant differences in their content of specific antibodies that ultimately affected the levels of these antibodies in treated patients. More specifically, Sandoglobulin® contained higher levels of antibodies to E. coli and S. epidermidis strains. Infusion of this preparation maintained the respective antibodies in the recipients significantly higher than those of healthy individuals. Gamimmune® infusion led to similar and comparable levels. Both IVIG preparations had comparable antibody titers towards K. pneumoniae, provided high amounts of antibodies, and kept recipients’ specific IgG at levels significantly higher than those of the healthy individuals. Enterococci spp . specific antibodies were significantly higher in Gamimmune®, whereas titers of antibodies towards S. aureus were comparable. Levels of antibodies against both Enterococci spp . and S. epidermidis after administration of both preparations were close to those in healthy individuals. None of the patients developed infection during the time of the study. In conclusion, most of the lots of the two IVIG preparations studied, despite some quantitative differences, provide patients with sufficient amounts of antibodies to bacterial surface antigens that protect them against infections.