PMID- 35154135
OWN - NLM
STAT- MEDLINE
DCOM- 20220328
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Enhanced Immunomodulatory Effect of Intravenous Immunoglobulin by Fc 
      Galactosylation and Nonfucosylation.
PG  - 818382
LID - 10.3389/fimmu.2022.818382 [doi]
LID - 818382
AB  - Intravenous immunoglobulin (IVIG) is used as an immunomodulatory agent in the 
      treatment of various autoimmune/inflammatory diseases although its mechanism of 
      action remains elusive. Recently, nonfucosylated IgG has been shown to be 
      preferentially bound to Fcgamma receptor IIIa (FcgammaRIIIa) on circulating natural 
      killer cells; therefore, we hypothesized that nonfucosylated IVIG may modulate 
      immune responses through FcgammaRIIIa blockade. Here, homogeneous fucosylated or 
      nonfucosylated glycoforms of normal polyclonal IgG bearing sialylated, 
      galactosylated or nongalactosylated Fc oligosaccharides were generated by 
      chemoenzymatic glycoengineering to investigate whether the IgG glycoforms can 
      inhibit antibody-dependent cellular cytotoxicity (ADCC).　Among the six IgG 
      glycoforms, galactosylated, nonfucosylated IgG [(G2)(2)] had the highest affinity 
      to FcgammaRIIIa and 20 times higher potency to inhibit ADCC than native IgG. A pilot 
      study of IVIG treatment in mice with collagen antibody-induced arthritis 
      highlighted the low-dose (G2)(2) glycoform of IVIG (0.1 g/kg) as an effective 
      immunomodulatory agent as the 10-fold higher dose of native IVIG. These 
      preliminary results suggest that the anti-inflammatory activity of IVIG is in 
      part mediated via activating FcgammaR blockade by galactosylated, nonfucosylated IgG 
      and that such nonfucosylated IgG glycoforms bound to FcgammaRs on immune cells play 
      immunomodulatory roles in health and disease. This study provides insights into 
      improved therapeutic strategies for autoimmune/inflammatory diseases using 
      glycoengineered IVIG and recombinant Fc.
CI  - Copyright (c) 2022 Mimura, Mimura-Kimura, Saldova, Rudd and Jefferis.
FAU - Mimura, Yusuke
AU  - Mimura Y
AD  - Department of Clinical Research, National Hospital Organization Yamaguchi Ube 
      Medical Center, Ube, Japan.
FAU - Mimura-Kimura, Yuka
AU  - Mimura-Kimura Y
AD  - Department of Clinical Research, National Hospital Organization Yamaguchi Ube 
      Medical Center, Ube, Japan.
FAU - Saldova, Radka
AU  - Saldova R
AD  - NIBRT GlycoScience Group, National Institute for Bioprocessing Research and 
      Training, Dublin, Ireland.
AD  - UCD School of Medicine, College of Health and Agricultural Science, University 
      College Dublin, Dublin, Ireland.
FAU - Rudd, Pauline M
AU  - Rudd PM
AD  - NIBRT GlycoScience Group, National Institute for Bioprocessing Research and 
      Training, Dublin, Ireland.
AD  - Bioprocessing Technology Institute, Agency for Science, Technology and Research, 
      Centros, Singapore.
FAU - Jefferis, Roy
AU  - Jefferis R
AD  - Institute of Immunology and Immunotherapy, College of Medical and Dental 
      Sciences, University of Birmingham, Birmingham, United Kingdom.
LA  - eng
PT  - Journal Article
DEP - 20220128
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (Receptors, IgG)
RN  - 28RYY2IV3F (Fucose)
RN  - 4F4X42SYQ6 (Rituximab)
SB  - IM
EIN - Front Immunol. 2022 Apr 01;13:902018. PMID: 35432361
MH  - Animals
MH  - Antibody-Dependent Cell Cytotoxicity/*immunology
MH  - Arthritis/*drug therapy
MH  - Fucose/immunology
MH  - Glycosylation
MH  - Humans
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Mice
MH  - Pilot Projects
MH  - Receptors, IgG/*immunology
MH  - Rituximab/*pharmacology
PMC - PMC8831331
OTO - NOTNLM
OT  - Fcgamma receptor
OT  - antibody-dependent cellular cytotoxicity
OT  - autoimmune disease
OT  - glycoengineering
OT  - intravenous immunoglobulin
OT  - natural killer cell
OT  - oligosaccharide
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/02/15 06:00
MHDA- 2022/03/29 06:00
PMCR- 2022/01/01
CRDT- 2022/02/14 05:30
PHST- 2021/11/19 00:00 [received]
PHST- 2022/01/10 00:00 [accepted]
PHST- 2022/02/14 05:30 [entrez]
PHST- 2022/02/15 06:00 [pubmed]
PHST- 2022/03/29 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.818382 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jan 28;13:818382. doi: 10.3389/fimmu.2022.818382. eCollection 
      2022.