Inflammation-induced enhancement of IgG immunoreactivity

Abstract

Natural polyreactive IgG antibodies are found in the sera of all healthy individuals. The in vitro exposure of pooled human IgG to protein-destabilizing chemical or physical factors has been previously shown to result in the exposure of their "hidden" polyspecificity. We hypothesize that such an enhancement of their pre-existing immunoreactivity may occur in vivo in the aggressive microenvironment of inflammation sites. An increase in the antigen binding intensity as well as of the number of recognized antigens was observed in the sera of IgG-infused immunodeficient SCID mice with induced local inflammation. The expansion of the IgG pathogen-binding repertoire may have important biological consequences.

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

“…Thus, exposure of these Abs to biologically relevant redox agents, such as reactive oxygen species, heme, iron ions, etc., results in a structural reorganization of their antigen-binding sites and acquisition of antigen-binding specificities to multiple unrelated antigens (32)(33)(34). Importantly, the substances that reveal the cryptic antibody polyreactivity are usually released in vivo at sites of inflammation or tissue damage and thus might modulate the antigen-binding properties of the susceptible Abs that are present in the immediate microenvironment (35). Biological functions and mechanism of antibodies with cryptic polyreactivity are not well understood.…”

Chorioamnionitis (ChA) modifies CX3CL1 (fractalkine) production by human amniotic epithelial cells (HAEC) under normoxic and hypoxic conditions

“…HAEC were isolated by the method of Okita et al as described elsewhere [32,33]. Briefly, immediately following delivery of the afterbirth (placenta), amnion samples of 6 × 6 cm were manually separated from the chorion, washed with phosphate-buffered saline (PBS) and incubated for 20 min with 5% trypsin (dilution 1:250; BD Difco™) at 37˚C to dispose of adherent cellular debris.…”

Antibody Polyreactivity in Health and Disease: Statu Variabilis

“…This may have in vivo relevance because large amounts of pro-oxidative molecules are released under certain pathological situations and upon recruitment and activation of neutrophils. Indeed, the exposure of IgG to sites of acute inflammation results in an increase in the total immunoreactivity of exogenously administrated polyclonal IgG preparations, probably due to uncovering of the cryptic polyreactivity of the sensitive Abs present in the Ig pool (48). Interestingly, the Abs with induced polyreactivity demonstrate powerful anti-inflammatory activity, as their administration in vivo resulted in a protective effect in models of septic shock and autoimmune diabetes (46,49).…”

“…In this respect, the role of Abs or BCRs with cryptic polyreactivity is intriguing. The expression of polyreactivity of these molecules occurs only in cases of severe inflammation and tissue damage (48). Rapid posttranslational diversification of Ag-binding repertoires may serve as an additional source of specificities that may be required for coping with infection and/or inflammation.…”