PMID- 29867943
OWN - NLM
STAT- MEDLINE
DCOM- 20190703
LR  - 20190703
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Potential of Murine IgG1 and Human IgG4 to Inhibit the Classical Complement and 
      Fcgamma Receptor Activation Pathways.
PG  - 958
LID - 10.3389/fimmu.2018.00958 [doi]
LID - 958
AB  - IgG antibodies (Abs) mediate their effector functions through the interaction 
      with Fcgamma receptors (FcgammaRs) and the complement factors. The main IgG-mediated 
      complement activation pathway is induced through the binding of complement C1q to 
      IgG Abs. This interaction is dependent on antigen-dependent hexamer formation of 
      human IgG1 and IgG3 to increase the affinity for the six-headed C1q molecule. By 
      contrast, human IgG4 fails to bind to C1q. Instead, it has been suggested that 
      human IgG4 can block IgG1 and IgG3 hexamerization required for their binding to 
      C1q and activating the complement. Here, we show that murine IgG1, which 
      functionally resembles human IgG4 by not interacting with C1q, inhibits the 
      binding of IgG2a, IgG2b, and IgG3 to C1q in vitro, and suppresses IgG2a-mediated 
      complement activation in a hemolytic assay in an antigen-dependent and IgG 
      subclass-specific manner. From this perspective, we discuss the potential of 
      murine IgG1 and human IgG4 to block the complement activation as well as 
      suppressive effects of sialylated IgG subclass Abs on FcgammaR-mediated immune cell 
      activation. Accumulating evidence suggests that both mechanisms seem to be 
      responsible for preventing uncontrolled IgG (auto)Ab-induced inflammation in mice 
      and humans. Distinct IgG subclass distributions and functionally opposite IgG Fc 
      glycosylation patterns might explain different outcomes of IgG-mediated immune 
      responses and provide new therapeutic options through the induction, enrichment, 
      or application of antigen-specific sialylated human IgG4 to prevent complement 
      and FcgammaR activation as well.
FAU - Lilienthal, Gina-Maria
AU  - Lilienthal GM
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
FAU - Rahmoller, Johann
AU  - Rahmoller J
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
AD  - Department of Anesthesiology and Intensive Care, University of Lubeck and 
      University Medical Center of Schleswig-Holstein, Lubeck, Germany.
FAU - Petry, Janina
AU  - Petry J
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
FAU - Bartsch, Yannic C
AU  - Bartsch YC
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
FAU - Leliavski, Alexei
AU  - Leliavski A
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
FAU - Ehlers, Marc
AU  - Ehlers M
AD  - Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutrition 
      Medicine, University of Lubeck and University Medical Center of 
      Schleswig-Holstein, Lubeck, Germany.
AD  - Airway Research Center North (ARCN), University of Lubeck, German Center for Lung 
      Research (DZL), Lubeck, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180509
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, IgG)
RN  - 0 (glycosylated IgG)
RN  - 80295-33-6 (Complement C1q)
SB  - IM
MH  - Animals
MH  - Binding Sites, Antibody
MH  - Complement Activation/*drug effects
MH  - Complement C1q/*antagonists & inhibitors/metabolism
MH  - *Complement Pathway, Classical
MH  - Glycosylation
MH  - Hemolysis
MH  - Humans
MH  - Immunoglobulin G/*pharmacology
MH  - Mice
MH  - Receptors, IgG/*antagonists & inhibitors
PMC - PMC5954034
OTO - NOTNLM
OT  - C1q
OT  - IgG
OT  - IgG glycosylation
OT  - IgG hexamer
OT  - IgG4
OT  - complement
OT  - immunosuppression
OT  - murine IgG1
EDAT- 2018/06/06 06:00
MHDA- 2018/06/06 06:01
PMCR- 2018/01/01
CRDT- 2018/06/06 06:00
PHST- 2018/01/31 00:00 [received]
PHST- 2018/04/17 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/06/06 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.00958 [doi]
PST - epublish
SO  - Front Immunol. 2018 May 9;9:958. doi: 10.3389/fimmu.2018.00958. eCollection 2018.