Accumulation of immunoglobulin G at focal sites of inflammation

Abstract

To evaluate the factors responsible for the accumulation of indium-111 immunoglobulin G (111In-IgG) at sites of inflammation, sequential measurements of tissue blood volume, interstitial fluid volume and accumulation of radiolabelled albumin and IgG were made in rats following Escherichia coli infection in the thigh. Compared with normal thigh muscle, there was approximately two-fold increase in interstitial fluid volume and approximately 1.5-fold increase in plasma and red blood cell volumes in infected muscle. For both proteins, there was a fivefold increase in influx rate constant (kin) in infected muscle. In normal muscle, the interstitial fluid concentration of labelled human serum albumin (111In-HSA) was significantly higher than that of 111In-IgG (P less than 0.01). In contrast, the concentrations in infected muscle were nearly identical. The concentration ratios (infected to normal muscle) were 1.7:1 for HSA and 3:1 for IgG. These data suggest that the infection imaging properties of 111In-IgG are related to expansion of the space available to macromolecules in infected tissue and increased transport into this space. At clinically important imaging times (24-48 h after injection), the higher target-to-background ratio of 111In-IgG compared with 111In-HSA is not due to the higher accumulation IgG in infected tissue but rather to the higher accumulation of HSA in normal tissue.

Staging the Initiation of Autoantibody-Induced Arthritis: A Critical Role for Immune Complexes

“…This would occur around 24-48 h, at which time the joint swelling is observed, and neutrophils are detectable histologically (18). The initiation of the inflammatory response would also cause long term changes in vascular permeability and improved access of Abs into the joint, as has been found in infectious foci of inflammation (44)(45)(46)(47), contributing to continued influx of autoantibodies and potential epitope spreading. Arthritis at this stage can also be reversed, as observed in the anti-GPI serum transfer model.…”

Clinical pharmacology considerations in biologics development

“…After cell entry, the FcRn recycling pathway can participate in the transcytosis step, in which mAbs can be bi-directionally transported to either the interstitial spaces or the vascular space [5][6][7] . The tissue distribution of mAbs may not be homogeneous because the tight binding between the mAb and its target can prohibit deeper penetration [8][9][10][11] . In contrast, this pattern is less prominent for small molecules, which can passively diffuse through a tissue.…”

Dissociation of indium from indium-111-labelled diethylene triamine penta-acetic acid conjugated non-specific polyclonal human immunoglobulin G in inflammatory foci

“…Release of "'In from both IgG and HSA provides an explanation for the high ratio between the concentrations of "'In-IgG and '"In-HSA in the interstitial fluid space of normal muscle and in plasma, which was reported by Juweid and co-workers [22]. A higher protein concentra tion in the interstitial fluid space of normal muscle than in plasma is very unlikely, since it would cause oedema.…”