Novel approach to monitor intravenous immunoglobulin pharmacokinetics in humans using polymorphic determinants in IgG1 constant domains. Issue 4 (24th December 2021)

• Record Type: Journal Article
• Authors: van Tilburg, Sander J.; Jacobs, Bart C.; Ooijevaar‐de Heer, Pleuni; Fokkink, Willem‐Jan R.; Huizinga, Ruth; Vidarsson, Gestur; Rispens, Theo
• Is Part Of: European journal of immunology. Volume 52:Issue 4(2022)
• Page Start: 609
• Page End: 617
• Publication Date: 2021-12-24
• Subjects: Intravenous immunoglobulin -- Pharmacokinetic -- IgG1 allotypes -- Monoclonal antibody -- Guillain–Barré syndrome; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202149653
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: Clinical efficacy of intravenous immunoglobulin treatment (IVIg) is related to its pharmacokinetic (PK) profile. Its usual evaluation, by measuring serum total IgG levels, is imprecise, because IVIg cannot be distinguished from endogenous IgG. We developed ELISAs to specifically monitor the PK of IVIg using the polymorphic determinants G1m(a), G1m(x), and G1m(f). The specificity of the IgG1 allotype assays was sufficient to determine IVIg concentrations as low as 0.1 mg/mL in sera from individuals not expressing the respective markers. IVIg was quantified in posttreatment serum from patients with Guillain–Barré syndrome (GBS) by measuring IgG1 allotypes not expressed endogenously. After serotyping, 27/28 GBS patients were found eligible for IVIg monitoring using one or two genetic markers. In 17 cases, IVIg levels could be determined by both anti‐G1m(a) and anti‐G1m(x) measurement, showing significant correlation. Longitudinal monitoring of IVIg PK in seven GBS patients showed potential differences in clearance of total IgG versus IVIg‐derived IgG, highlighting that total IgG measurements may not accurately reflect IVIg PK. To summarize, anti‐IgG1 allotype assays can discriminate between endogenous IgG and therapeutic polyclonal IgG. These assays will be an important tool to better understand the variability in IVIg PK and treatment response of all patients treated with IVIg. Abstract : Clinical efficacy of intravenous immunoglobulin treatment (IVIg) is related to its pharmacokinetic profile, which cannot easily be monitored specifically. We developed assays to specifically monitor the pharmacokinetics of IVIg using polymorphic determinants of IgG1, which allows discrimination between endogenous IgG and therapeutic polyclonal IgG.