Serum IgM, IgG and IgA block by F(ab′)<sub>2</sub>‐dependent mechanism the binding of natural IgG autoantibodies from therapeutic immunoglobulin preparations to self‐antigens

Djoumerska, I.; Tchorbanov, Andrey; Donkova-Petrini, Vladimira; Pashov, Anastas; Vassilev, Tchavdar

doi:10.1111/j.1600-0609.2004.00350.x

Cited by 8 publications

(11 citation statements)

References 58 publications

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“…The half-life of the intravenously administered IgG autoantibodies depends on the heightened IgG catabolism, stimulated by its higher plasma concentration after the infusion [36], on the binding of natural autoantibodies to the tissues [37] and on the F(ab 0 ) 2 -dependent (idiotype) interactions of the infused IgG with the IgM, IgA and IgG from the patient's plasma [38,39,40]. The importance of the presence of autoantibodies for the beneficial immunomodulatory and anti-inflammatory effects of IVIg infusions in autoimmune patients has never been directly tested.…”

Section: Discussionmentioning

confidence: 99%

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

et al. 2005

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Natural immunoglobulin G (IgG) autoantibodies are present in the plasma of healthy individuals and, as a result, in pooled therapeutic intravenous immunoglobulin (IVIg) preparations. The production processes of commercial IVIg preparations involve different fractionation and virus-inactivation steps that include in some cases treatments at extreme conditions. Different physical and chemical treatments are known to augment greatly the reactivity of natural autoantibodies to self-antigens. It is not clear to what extent the self-reactivity of IVIg preparations is due to the presence of natural IgG antibodies in the plasma pools used for fractionation, and to what extent it is due to the treatments that the IgG molecules have been subjected to during the fractionation process. We compared the binding of seven different commercial IVIg preparations to human liver antigens. All studied IVIg's could be clearly separated into two distinct groups: those that possess significant self-reactivity and those with low binding to self-antigens. Increased self-binding was seen in the preparations produced using a fractionation step at low pH. The treatment of IVIg at low pH resulted in increasing the inhibitory effect of the pooled IgG on PHA-induced proliferation of human peripheral blood mononuclear cells. IVIg's with high and low self-binding may have different immunomodulating activities when infused to autoimmune patients.

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Section: Discussionmentioning

confidence: 99%

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

et al. 2005

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“…These adverse reactions seem to be mediated by proinflammatory cytokines and depend on both the percentage of dIgG within the IVIg preparation and the infusion rate 13 . The adverse effects, occurring within minutes post infusion and lasting up to 24 h, might be due to the dimerized state of the Ig being perceived as a considerable influx of immune complexes (ICs), functioning as a proinflammatory stimulus 14,15 …”

Section: Introductionmentioning

confidence: 99%

“…13 The adverse effects, occurring within minutes post infusion and lasting up to 24 h, might be due to the dimerized state of the Ig being perceived as a considerable influx of immune complexes (ICs), functioning as a proinflammatory stimulus. 14,15 In parallel, many studies have described the existence of self-reactive Abs within normal human serum and therapeutic IVIg preparations. [16][17][18][19][20][21][22][23] These circulating self-reactive antibodies are thought to be controlled by anti-idiotypic interactions, and belong to the normal constituents of immune homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Self‐Reactivity in the Dimeric Intravenous Immunoglobulin Fraction

Schaub¹,

Wymann²,

Heller³

et al. 2007

Annals of the New York Academy of Sciences

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Therapeutic intravenous immunoglobulin (IVIg) preparations contain antibodies reflecting the cumulative antigen experience of the donor population. IVIg contains variable amounts of monomeric and dimeric IgG, but there is little information available on their comparative antibody specificities. We have isolated highly purified fractions of monomeric and dimeric IgG by size-exclusion chromatography. Following treatment of all fractions at pH4, analyses by immunodot and immunocytology on human cell lines showed a preferential recognition of autoantigens in the dimeric IgG fraction. Investigation of the HEp-2 cytoplasmic proteome by 2D-PAGE, Western blot, and subsequent identification of IVIg reactive spots by mass spectrometry (LC-MS/MS) showed that IVIg recognized only a restricted set of the total proteins. Similar experiments showed that more antigens were recognized by the dimeric IgG fraction, especially when the dissociated dimer fraction was used, as compared to its monomeric counterpart. These observations are consistent with idiotype-anti-idiotype masking of auto-specific Abs in the dimeric fraction of IVIg.

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“…We show that serum IgM and IgA block the binding of IgG to human liver antigens. The blocking of pIgG antibodies by serum IgG molecules was demonstrated in our previous study . These interactions could mask the self‐reactivity in vivo and are a possible mechanism to maintain the tolerance to the self‐antigens in healthy individuals.…”

Section: Discussionmentioning

confidence: 72%

Serum or breast milk immunoglobulins mask the self‐reactivity of human natural IgG antibodies

Djoumerska-Alexieva

Manoylov

Dimitrov

et al. 2013

APMIS

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B cells producing IgG antibodies specific to a variety of self- or foreign antigens are a normal constituent of the immune system of all healthy individuals. These naturally occurring IgG antibodies are found in the serum, external secretions, and pooled human immunoglobulin preparations. They bind with low affinity to antigens, which can also be targets for pathologic autoantibodies. An enhancement of naturally occurring IgG autoantibody activity was observed after treatment of human IgG molecules with protein-destabilizing agents. We have investigated the interactions of human immunoglobulins that were obtained from serum or from breast milk of healthy individuals or IVIg with human liver antigens. Proteins from an individual serum or milk were isolated by two methods, one of which included exposure to low pH and the other did not. Purified serum, mucosal IgM, IgA, and the fraction containing immunoglobulin G F(ab')2 fragments each inhibited the binding of a single donor or pooled IgG to human liver antigens. Our study presents findings regarding the role of the breast milk or serum antibodies in blocking the self-reactivity of IgG antibodies. It supports the suggestion that not IVIg only, but also the pooled human IgM and IgA might possess a potent beneficial immunomodulatory activity in autoimmune patients.

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Serum IgM, IgG and IgA block by F(ab′)₂‐dependent mechanism the binding of natural IgG autoantibodies from therapeutic immunoglobulin preparations to self‐antigens

Cited by 8 publications

References 58 publications

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

Self‐Reactivity in the Dimeric Intravenous Immunoglobulin Fraction

Serum or breast milk immunoglobulins mask the self‐reactivity of human natural IgG antibodies

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Serum IgM, IgG and IgA block by F(ab′)2‐dependent mechanism the binding of natural IgG autoantibodies from therapeutic immunoglobulin preparations to self‐antigens

Cited by 8 publications

References 58 publications

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

The Autoreactivity of Therapeutic Intravenous Immunoglobulin (IVIg) Preparations Depends on the Fractionation Methods Used

Self‐Reactivity in the Dimeric Intravenous Immunoglobulin Fraction

Serum or breast milk immunoglobulins mask the self‐reactivity of human natural IgG antibodies

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Product

Resources

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Serum IgM, IgG and IgA block by F(ab′)₂‐dependent mechanism the binding of natural IgG autoantibodies from therapeutic immunoglobulin preparations to self‐antigens