To cite this article: Schaub A, von Gunten S, Vogel M, Wymann S, Rüegsegger M, Stadler BM, Spycher M, Simon H-U, Miescher S. Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their anti-idiotypes. Allergy 2011; 66: 1030–1037.
Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.