PMID- 21029072
OWN - NLM
STAT- MEDLINE
DCOM- 20110308
LR  - 20211020
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 162
IP  - 3
DP  - 2010 Dec
TI  - Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy 
      of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP).
PG  - 415-24
LID - 10.1111/j.1365-2249.2010.04255.x [doi]
AB  - Intravenous immunoglobulin (IVIG) has been used widely to treat immune 
      thrombocytopenic purpura (ITP), but the mechanisms of its action remain unclear. 
      We investigated the affinity for Fcgamma receptors (FcgammaRs) and the 
      thrombocytopenia-ameliorating effect of S-sulfonated gammaglobulin (SGG) and 
      S-alkylated gammaglobulin (AGG), in comparison with unmodified gammaglobulin 
      (GG), in a mouse ITP model. Cleavage of immunoglobulin (Ig)G interchain disulfide 
      bonds by either S-sulfonation or S-alkylation did not decrease the affinity for 
      FcgammaRIIA (CD32A) and FcgammaRIIB (CD32B), but did decrease the affinity for FcgammaRIA 
      (CD64A) and FcgammaRIIIA (CD16A), presumably because of changes in H-chain 
      configuration. The interchain disulfide bond cleavage decreased the affinity much 
      more for mouse FcgammaRIV than for mouse FcgammaRIIB. The ability of AGG to ameliorate 
      ITP was greatly diminished, while SGG, whose disulfide bonds are reconstituted in 
      vivo, was as effective as GG. These results suggest that the interchain disulfide 
      bonds are important for therapeutic effect. It is also suggested that the 
      interaction of IVIG with the inhibitory receptor FcgammaRIIB is insufficient for 
      effective amelioration of ITP and that, at least in this model, direct binding of 
      IVIG to FcgammaRIIIA is also required.
CI  - (c) 2010 The Authors. Clinical and Experimental Immunology (c) 2010 British Society 
      for Immunology.
FAU - Machino, Y
AU  - Machino Y
AD  - Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, 
      Japan.
FAU - Ohta, H
AU  - Ohta H
FAU - Suzuki, E
AU  - Suzuki E
FAU - Higurashi, S
AU  - Higurashi S
FAU - Tezuka, T
AU  - Tezuka T
FAU - Nagashima, H
AU  - Nagashima H
FAU - Kohroki, J
AU  - Kohroki J
FAU - Masuho, Y
AU  - Masuho Y
LA  - eng
PT  - Journal Article
DEP - 20101005
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (IgG, sulfonated)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Alkylation
MH  - Animals
MH  - Antibody Affinity/*drug effects
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Humans
MH  - Immunoglobulin G/*administration & dosage/adverse effects/chemistry
MH  - Immunoglobulins, Intravenous/*administration & dosage/adverse effects/chemistry
MH  - *Immunotherapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Purpura, Thrombocytopenic, Idiopathic/*drug therapy/immunology/physiopathology
MH  - Receptors, IgG/chemistry/metabolism
MH  - Treatment Outcome
PMC - PMC3026545
EDAT- 2010/10/30 06:00
MHDA- 2011/03/09 06:00
PMCR- 2011/12/01
CRDT- 2010/10/30 06:00
PHST- 2010/10/30 06:00 [entrez]
PHST- 2010/10/30 06:00 [pubmed]
PHST- 2011/03/09 06:00 [medline]
PHST- 2011/12/01 00:00 [pmc-release]
AID - 10.1111/j.1365-2249.2010.04255.x [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2010 Dec;162(3):415-24. doi: 10.1111/j.1365-2249.2010.04255.x. 
      Epub 2010 Oct 5.