PMID- 21385183
OWN - NLM
STAT- MEDLINE
DCOM- 20111206
LR  - 20171116
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 66
IP  - 8
DP  - 2011 Aug
TI  - Dimeric IVIG contains natural anti-Siglec-9 autoantibodies and their 
      anti-idiotypes.
PG  - 1030-7
LID - 10.1111/j.1398-9995.2011.02579.x [doi]
AB  - 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.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Schaub, A
AU  - Schaub A
AD  - University Institute of Immunology, Bern, Switzerland CSL Behring AG, Bern, 
      Switzerland.
FAU - von Gunten, S
AU  - von Gunten S
FAU - Vogel, M
AU  - Vogel M
FAU - Wymann, S
AU  - Wymann S
FAU - Ruegsegger, M
AU  - Ruegsegger M
FAU - Stadler, B M
AU  - Stadler BM
FAU - Spycher, M
AU  - Spycher M
FAU - Simon, H-U
AU  - Simon HU
FAU - Miescher, S
AU  - Miescher S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110309
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (Antigens, CD)
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin Idiotypes)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Lectins)
RN  - 0 (SIGLEC9 protein, human)
RN  - 0 (Sialic Acid Binding Immunoglobulin-like Lectins)
RN  - 0 (fas Receptor)
SB  - IM
MH  - Antigens, CD/*immunology
MH  - Autoantibodies/*analysis
MH  - Humans
MH  - Immunoglobulin Idiotypes/*analysis
MH  - Immunoglobulins, Intravenous/*analysis/immunology
MH  - Lectins/*immunology
MH  - Neutrophils
MH  - Protein Multimerization
MH  - Sialic Acid Binding Immunoglobulin-like Lectins
MH  - fas Receptor/immunology
EDAT- 2011/03/10 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/03/10 06:00
PHST- 2011/03/10 06:00 [entrez]
PHST- 2011/03/10 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1111/j.1398-9995.2011.02579.x [doi]
PST - ppublish
SO  - Allergy. 2011 Aug;66(8):1030-7. doi: 10.1111/j.1398-9995.2011.02579.x. Epub 2011 
      Mar 9.