Comparative Analysis of Antigen Specificities in the Monomeric and Dimeric Fractions of Intravenous Immunoglobulin

Miescher, Sylvia; Schaub, Alexander; Ghielmetti, Marco; Baumann, Michael; Vogel, Monique; Bolli, Reinhard; Stadler, Beda M.

doi:10.1196/annals.1361.102

Cited by 14 publications

(10 citation statements)

References 44 publications

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“…Numerous previous observations document that IVIg is capable of recognizing human self‐proteins 20 . In contrast, studies assessing the reactivity of different immunoglobulin fractions resulting from separation by size‐exclusion chromatography are scarce 26 . Following the dissociation of IVIg and IVIg‐derived fractions by pH 4 treatment, we employed these fractions to quantify the overall reactivity toward self‐proteins by immunodot assays on HEp‐2 (.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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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Section: Resultsmentioning

confidence: 99%

“…IVIg (Sandoglobulin; kindly provided by CSL Behring, AG, Bern, Switzerland) and IVIg‐derived mIgG and dIgG fractions were separated by size‐exclusion chromatography on a ReproSil 300 × 20 mm column as previously described 26 …”

Section: Methodsmentioning

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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“…Monomers represent the monomeric IgG (molecular weight approximately 150 KDa), dimers represent 2 IgG molecules, which can be oriented in various forms, including the classical idiotype anti-idiotype pairs. Both forms showed reactivity in biochemical analysis by immunodot, ELISA, FACS and immunohistology with a preferential reactivity of the dimeric form on a va-riety of both self-antigens and exoantigens [53]. Polymers consisting of several IgG molecules are formed under harsh conditions in the production process and cannot be dissolved once denatured.…”

Section: Size Exclusion Chromatographymentioning

confidence: 99%

Purification of intravenous immunoglobulin G from human plasma – aspects of yield and virus safety

Buchacher

Iberer

2006

Biotechnology Journal

110

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Plasma-derived intravenous immunoglobulin (IVIG) preparations have been successfully applied for the prophylactic prevention of infectious diseases in immunodeficient patients. In addition to its replacement therapy of primary and secondary antibody deficiencies, IVIG has found increased use in autoimmune and inflammatory diseases. IVIG has become the major plasma product on the global blood product market. The world wide consumption nearly tripled between 1992 and 2003, from 19.4 to 52.6 tons. Classical manufacturing processes of IVIG, but also new strategies for purification are discussed with respect to practicability and yield. Ethanol fractionation is still the basis for most IVIG processes, although isolation and purification of immunoglobulin G (IgG) by chromatography has gained ground. The efficiency of virus inactivation methods and virus removal techniques in terms of logarithmic reduction factors are analyzed, but also the IgG losses are taken into consideration. Some of these methods also have the ability to separate prions. High pathogen safety and high yields have become the dominant goals of the plasma fractionation industry.

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“…Polyreactivity supports the neutralization of monomers by dimer formation. However, the monomer-dimer distribution of concn and affinity of a given ab specificity may also depend on the given network of Vab-anti-Vab and/or Id-anti-Id interactions in the md-IgG preparation and may be connected with the experimentally observed preferential ab reactivity to a variety of self-and exoags, embodied in the IgG-dimer fraction (Miescher et al 2005).…”

Section: Potential Origin and Consequences Of Polyreactivitymentioning

confidence: 99%