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Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect

Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect
Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect
Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.
0006-4971
3136-3142
Bleeker, Wim.K.
11ce7c46-56b6-4e31-95fc-bbc02d96dd07
Teeling, Jessica.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Hack, C.Erik
f2a19948-e2ab-4747-962f-e6d46921a243
Bleeker, Wim.K.
11ce7c46-56b6-4e31-95fc-bbc02d96dd07
Teeling, Jessica.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Hack, C.Erik
f2a19948-e2ab-4747-962f-e6d46921a243

Bleeker, Wim.K., Teeling, Jessica.L. and Hack, C.Erik (2001) Accelerated autoantibody clearance by intravenous immunoglobulin therapy: studies in experimental models to determine the magnitude and time course of the effect. Blood, 98 (10), 3136-3142. (doi:10.1182/blood.V98.10.3136).

Record type: Article

Abstract

Recently, it has been postulated that the beneficial effect of intravenous immunoglobulins (IVIGs) in antibody-mediated autoimmune disorders is based on accelerated catabolism of autoantibodies. In the current study, in vivo experiments were performed with mice in which autoantibody production was mimicked by continuous infusion of monoclonal antibodies. In this model, a single dose of IVIG reduced the plasma concentrations of the infused immunoglobulin (Ig)G1 monoclonal antibody (mAb) by approximately 40% after 3 days, whereas the concentration of an IgA mAb was not affected. To extrapolate these findings to humans, a computational model for IgG clearance was established that accurately predicted the time course and magnitude of the decrease in IgG plasma levels observed in mice. Adapted for humans, this model predicted a gradually occurring decrease in autoantibody levels after IVIG administration (2 g/kg), with a maximum reduction of approximately 25% after 3 to 4 weeks and a continued decrease of several months. In conclusion, a single high dose of IVIG induces a relatively small but long-lasting reduction of autoantibody levels by accelerated IgG clearance. This mechanism has clinical relevance in the sense that it can fully explain, as the sole mechanism, the gradual decrease in autoantibody levels observed in several patient studies. However, in some clinical studies, larger or more rapid effects have been observed that cannot be explained by accelerated clearance. Hence, IVIG can also reduce autoantibody levels through mechanisms such as down-regulation of antibody production or neutralization by anti-idiotypic antibodies.

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Published date: 15 November 2001

Identifiers

Local EPrints ID: 56142
URI: https://eprints.soton.ac.uk/id/eprint/56142
ISSN: 0006-4971
PURE UUID: ad33c89f-e908-4ab7-be34-a034a9c5d61d

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Date deposited: 07 Aug 2008
Last modified: 13 Mar 2019 20:35

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