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Allergy. 2011 Aug;66(8):1030-7. doi: 10.1111/j.1398-9995.2011.02579.x. Epub 2011 Mar 9.

Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes.

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  • 1University Institute of Immunology, Bern, Switzerland CSL Behring AG, Bern, Switzerland.



Intravenous immunoglobulin (IVIG) preparations are increasingly used for the treatment of autoimmune and chronic inflammatory diseases. Naturally occurring autoantibodies against Siglec-9 and Fas are thought to contribute to the anti-inflammatory effects of IVIG via cell death regulation of leukocytes and tissue cells. Dimeric IVIG fractions are suspected to contain idiotypic (Id)-anti-idiotypic complexes of antibodies, which might also include anti-Siglec-9 and anti-Fas autoantibodies.


Dimeric IVIG fractions were separated from monomeric IVIG by size-exclusion chromatography and remonomerized by low pH treatment. Binding studies of total, monomeric, and dimeric IVIG were performed using surface plasmon resonance and flow cytometry on primary human neutrophils.


Anti-Siglec-9 and anti-Fas autoantibodies were contained in both monomeric and dimeric IVIG fractions, but anti-Siglec-9 antibodies were highly enriched in dimeric IVIG. The propensity to engage in dimer formation was paratope dependent. IVIG binding to Siglec-9 was specific and sialylation independent. Interestingly, we detected anti-idiotypic antibodies (anti-Ids) against anti-Siglec-9 autoantibodies in dimeric, but not in monomeric fractions of IVIG.


Our study supports the concept that idiotype-anti-idiotype (Id-anti-Id) interactions contribute to the dimer formation in IVIG preparations. To our knowledge, this is the first description of Id-anti-Id dimers of death receptor-specific antibodies in IVIG. Such Id-anti-Id interactions might determine the activity of immunomodulatory antibodies present both in IVIG and the patient.

© 2011 John Wiley & Sons A/S.

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