Intravenous immunoglobulin contains a broad repertoire of anticarbohydrate antibodies that is not restricted to the IgG2 subclass

Abstract

Background Specificities for carbohydrate IgG antibodies, thought to be predominantly of the IgG2 subclass, have never been broadly examined in healthy human subjects. Objective To examine commercial intravenous immunoglobulin (IVIg) preparations for their ability to recognize a wide range of glycans and to determine the contribution of IgG2 to the binding pattern observed. Methods We employed a glycan microarray to evaluate IVIg preparations and a control mix of similar proportions of human myeloma IgG1 and IgG2 for binding to 377 glycans courtesy of the Consortium for Functional Glycomics Core H (http://www.functionalglycomics.org/static/consortium/resources/resourcecoreh8.shtml). Glycans recognized were categorized using public databases for their likely cellular sources. IgG2 was depleted from IVIg using immunoaffinity chromatography and depletion confirmed using nephelometry and surface plasmon resonance. Results Nearly half of the glycans bound IgG. Some of the glycans with the greatest antibody binding can be found in structures of human pathogenic bacteria (e.g., Streptococcus pneumoniae, Mycobacterium tuberculosis, Vibrio cholera) and non-pathogenic bacteria, including lipopolysaccharide and lipoteichoic acid, capsular polysaccharides and exopolysaccharides. Surprisingly, depletion of IgG2 had only a modest effect on anti-carbohydrate recognition patterns compared to the starting IVIg preparation. Little to no binding activity was detected to human endogenous glycans including tumor-associated antigens. Conclusions This novel, comprehensive analysis provides evidence that IVIg contains a much wider range than previously appreciated of anti-carbohydrate IgG antibodies, including those recognizing both pathogenic and non-pathogen-associated prokaryotic glycans.

Human IgA Fc Receptor FcαRI (CD89) Triggers Different Forms of Neutrophil Death Depending on the Inflammatory Microenvironment

“…Reflecting the Ag experience of the donor population, human Ig preparations contain broad reactivity to carbohydrate or protein molecules (10,52,53), some of which exhibit immunomodulatory functions, including the regulation of neutrophil death (11,54). For this reason and in contrast to the study by Schettini et al (20), who used immobilized plasma or secretory IgA, we assessed the effect of immobilized monoclonal IgA1 or IgA2 with irrelevant specificity on neutrophil death.…”

Immunoglobulin G Subclass Responses to Recombinant Em18 in the Follow-Up of Patients with Alveolar Echinococcosis in Different Clinical Stages

“…In our study, IgG1 levels against Em18 were also increased at all clinical stages, whereas IgG2 demonstrated the lowest positive median indices at all stages, and IgG3 was completely undetectable. Since Em18 is a pure protein antigen, and IgG2 has often been associated with anticarbohydrate immune responses in humans (17), it is understandable that only a low IgG2 response was obtained. Why IgG3 was undetectable in our study is less clear.…”

“…Why IgG3 was undetectable in our study is less clear. A greaterthan-expected proportion of carbohydrate-specific IgG antibody responses in humans can have a non-IgG2 subclass origin (17), possibly also encompassing IgG3. Hypothetically, a suppression of IgG3 responses toward this diagnostic antigen by the parasite might also be possible.…”

The (1→6)-β-Glucan Moiety Represents a Cross-Reactive Epitope of Infection-Induced Malignancy Surveillance

“…Healthy human subjects possess high titer natural Abs (nAbs; mostly IgM, some IgG and IgA) in their circulation that can recognize a variety of Ags (14,(23)(24)(25)(26)(27), mostly carbohydrates that can be classified into three groups: 1) allotransplantation and xenotransplantation Ags (e.g., ABO blood group Ags and a-gal epitopes [Gala1-3Galb1-4GlcNAc-R]) (14,(23)(24)(25); 2) cell-wall components of microorganisms such as b-glucans (24-27); and 3) TACAs (14,15,23). Cross-recognition of the first two groups by the human nAbs is well established (14,(23)(24)(25), but whether human nAbs cross-recognize TACAs and PAMPs has rarely been investigated.…”

“…Cross-recognition of the first two groups by the human nAbs is well established (14,(23)(24)(25), but whether human nAbs cross-recognize TACAs and PAMPs has rarely been investigated. Identification and characterization of microbial carbohydrate Ags capable of inducing antitumor Abs in vivo will provide useful clues for the molecular mimicry hypothesis explaining the antitumor beneficial effect of microbial infections in humans.…”