Immunoglobulin G dimer: An idiotype-anti-idiotype complex

Tankersley, Donald L.; Preston, M S; Finlayson, J. S.

doi:10.1016/0161-5890(88)90088-0

Cited by 134 publications

(82 citation statements)

References 12 publications

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“…18 This study revealed that commercially available IVIG preparations contain variable amounts of IgG dimers (range, 5%-15%). This is consistent with the observations of Tankersley et al 19 that IgG dimers are a normal constituent of IVIG prepared from a large donor pool. The amount of dimers in the preparations mainly depends on the pool size and the storage conditions.…”

Section: Discussionsupporting

confidence: 82%

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia

Teeling

Jansen-Hendriks²,

Kuijpers³

et al. 2001

Blood

166

145

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The clinical benefit of intravenous immunoglobulin (IVIG) preparations in the treatment of immune thrombocytopenic purpura (ITP) is supposed to be mediated by blockade of Fc␥ receptor-bearing phagocytes. In 2 experimental models for ITP, it is shown that the therapeutic efficacy of IVIG preparations is related to the IgG dimer content present in these preparations. A rat monoclonal antibody (mAb; MWReg30) directed to the murine plateletspecific integrin ␣ IIb ␤ 3 (gpIIb/IIIa) was administered intraperitoneally either as bolus injection or continuous infusion. With bolus injection, the circulating platelet count dropped to almost zero within 3 hours. Pretreatment with cobra venom factor did not affect platelet depletion, whereas pretreatment with anti-Fc␥RII/III mAb 2.4G2 or IVIG greatly reduced platelet clearance. With continuous infusion, platelet numbers reached a steady state after 4 days, at approximately 25% of control. This reduction in platelets was, however, not observed in mice deficient for the FcR␥-chain, lacking Fc␥RI, Fc␥RIII, and Fc␥RIII ؊/؊ mice. Infusion of a single dose of IVIG with a high IgG dimer content on the 4th day-ie, mimicking therapeutic administration-resulted in a platelet increase for several days. IVIG predominantly consisting of monomeric IgG had no effect on platelet numbers. In conclu

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Section: Discussionsupporting

confidence: 82%

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia

Teeling

Jansen-Hendriks²,

Kuijpers³

et al. 2001

Blood

166

145

View full text Add to dashboard Cite

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“…As shown by others (38), the pooled human IgG preparation contained monomeric and dimeric IgG (Fig. 1 Binding ofcytokines to papain-treated IgG.…”

Section: Resultsmentioning

confidence: 99%

“…Pools of human immune globulin have been shown to contain dimeric IgG, which has been proposed to constitute idiotype-anti-idiotype pairs (38,40). However, compared with unfractionated and monomeric IgG, dimeric IgG did not differ in their specific binding of '251-IL-lIa and '251-IL-6, indicating the absence of appreciable amounts of blocking anti-idiotype antibodies.…”

Section: Resultsmentioning

confidence: 99%

“…Similar analyses using 125M-IL-1 a, '25I-IL-6 as well as nondenatured and heatdenatured 125I-IL-I(3 did not show a time-or concentration-dependent change in the distribution between the monomeric and polymeric forms of the cytokines. Because ofthe concentration-dependent distribution ofthe monomeric and trimeric forms of 1251-TNFa, binding to IgG was calculated with regard to both forms of the cytokine: (38) 5 (0.5) 9 (6.3) 5 (2) Human IgG (Nordimmun®), 6 mg/ml, was preincubated for 2 h in PBS with the additives indicated. The preparations were then incubated with labeled and with or without excess unlabeled cytokine.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Svenson¹,

Hansen²,

Bendtzen³

1993

J. Clin. Invest.

114

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“…To remove this contaminating dimeric IgG, IVIg was dialysed to low pH, resulting in the disruption of any dimers formed (21). Furthermore, control experiments, in which we tested the effect of small amounts of dimeric IgG, revealed that small amounts of contaminating dimers (Ͻ0.5%) in the monomeric IgG fraction cannot explain the inhibiting effect of monomeric IgG on the binding of dimeric IgG to Fc␥RIIa-transfected cells (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Monomeric IgG in Intravenous Ig Preparations Is a Functional Antagonist of FcγRII and FcγRIIIb

Mirre

Teeling

Meer

et al. 2004

The Journal of Immunology

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Intravenous Ig preparations (IVIg), originally developed as a substitution therapy for patients with low plasma IgG, are nowadays frequently used in the treatment of various immune diseases. However, the mechanism of action of IVIg in these diseases remains elusive and is often referred to as “immunomodulatory.” We hypothesized that monomeric IgG may act as a low-affinity FcγR antagonist and sought experimental evidence for this hypothesis. Human neutrophils as well FcγRIIa-transfected IIA1.6 cells were used as FcγR-positive cells and aggregated IgG (aIgG) or stable dimeric IgG as FcγR-specific agonists for these cells. We found that monomeric IgG purified from IVIg at concentrations similar to that of IgG in plasma, diminished the binding of stable dimeric IgG to FcγRIIa transfectants, reduced aIgG-induced influx of Ca2+ ions into the cytosol of neutrophils, and attenuated the aIgG-induced release of elastase. Notably, monomeric IgG by itself did not elicit these responses, nor did it affect these processes in response to fMLP. Absorption of IgG from normal plasma revealed that plasma IgG exerted similar effects as monomeric IgG in IVIg. In addition, adding monomeric IgG to blood of healthy volunteers showed a dose-dependent decrease of aIgG-induced elastase release. Finally, we observed decreased aIgG-induced polymorphonuclear neutrophil responses in two hypogammaglobulinemic patients upon treatment with IVIg. We conclude that monomeric IgG at physiological levels acts as a low-affinity FcγR antagonist. Moreover, FcγR antagonism constitutes an immunomodulatory effect of IVIg.

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Immunoglobulin G dimer: An idiotype-anti-idiotype complex

Cited by 134 publications

References 12 publications

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia

Therapeutic efficacy of intravenous immunoglobulin preparations depends on the immunoglobulin G dimers: studies in experimental immune thrombocytopenia

Binding of cytokines to pharmaceutically prepared human immunoglobulin.

Monomeric IgG in Intravenous Ig Preparations Is a Functional Antagonist of FcγRII and FcγRIIIb

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