Decreased protective efficacy of reduced and alkylated human immune serum globulin in experimental infection with Haemophilus influenzae type b
- 1 January 1985
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 47 (1) , 142-148
- https://doi.org/10.1128/iai.47.1.142-148.1985
Abstract
Conventionally prepared immune serum globulin frequently produces severe side effects when administered intravenously. A modified preparation in which 4 to 5 interchain disulfide bonds have been reduced and alkylated has been made for intravenous use. However, reduction and alkylation may affect Fc-mediated functions of immunoglobulin G, particularly its ability to fix complement by the classical pathway. To determine whether reduction and alkylation alters the protective activity of immune serum globulin in vivo we compared it with two less harshly prepared globulins (pH 4 treated or ultrafiltered) in an infant rat model of Haemophilus influenzae b infection. Antibody binding to the capsular and noncapsular components of H. influenzae b and in vitro bactericidal activity were similar in the globulin preparations. Infant rats were treated with various doses of globulins adjusted to provide identical concentrations of anticapsular antibodies as measured by the Farr radioactive antigen binding assay. At high doses of anticapsular antibody (greater than 1,500 ng per pup), all preparations protected well. At marginal doses (750 ng per pup), however, rats given reduced and alkylated globulin had a significantly greater incidence of bacteremia (P less than 0.05), meningitis (P less than 0.01), and death (P less than 0.05) and a higher magnitude of bacteremia (P less than 0.02) than rats who received pH4-treated or ultrafiltered globulins. These differences were not due to differences in anticapsular antibody concentrations achieved in the serum. The 50% protective serum concentrations of anticapsular antibody in this model were 200 to 300 ng/ml for reduced and alkylated globulin and 100 to 200 ng/ml for acid-treated globulin. Absorption of the globulins with purified H. influenzae b capsule reduced in vitro bactericidal activity and rat protective activity. However, the magnitude of bacteremia was lower in rats receiving absorbed pH 4-treated globulin than in those receiving absorbed reduced and alkylated globulin (P less than 0.05). We conclude that reduced and alkylated immunoglobulin G provides significantly less protective activity against H. influenzae b infection in this model than globulins not so modified, and we suggest that the altered Fc function of the immunoglobulin G, such as the decreased ability to fix complement by the classical pathway or decreased Fc-mediated opsonization, may be responsible for this impairment.This publication has 29 references indexed in Scilit:
- Protective efficacy of a modified immune serum globulin in experimental group B streptococcal infectionThe Journal of Pediatrics, 1981
- A New Preparation of Modified Immune Serum Globulin (Human) Suitable for Intravenous AdministrationVox Sanguinis, 1981
- Preparation of a Stable Intravenous Gamma‐Globulin: Process Design and Scale‐UpVox Sanguinis, 1980
- The role of specific antibody in alternative complement pathway-mediated opsonophagocytosis of type III, group B Streptococcus.The Journal of Experimental Medicine, 1980
- Role of Immunity in the Clearance of Bacteremia Due to Haemophilus influenzaeThe Journal of Infectious Diseases, 1978
- Reduced immunoglobulin G activates complement system with decreased cooperativityBiochemical and Biophysical Research Communications, 1978
- Rapid diagnosis of Hemophilus influenzae type b infections by latex particle agglutination and counterimmunoelectrophoresisThe Journal of Pediatrics, 1978
- COMPLEMENT DEFICIENCY STATESMedicine, 1978
- Recurrent haemophilus septicaemia and immunoglobulin deficiency.Archives of Disease in Childhood, 1970
- The Separation of the Antibodies, Isoagglutinins, Prothrombin, Plasminogen and β1-Lipoprotein into Subfractions of Human PlasmaJournal of the American Chemical Society, 1949