PMID- 28223071
OWN - NLM
STAT- MEDLINE
DCOM- 20170818
LR  - 20181113
IS  - 1521-7035 (Electronic)
IS  - 1521-6616 (Print)
IS  - 1521-6616 (Linking)
VI  - 179
DP  - 2017 Jun
TI  - Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits 
      autoimmune arthritis.
PG  - 8-16
LID - S1521-6616(16)30605-2 [pii]
LID - 10.1016/j.clim.2017.01.016 [doi]
AB  - Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with 
      no known cure. Recently, we identified the immunomodulatory enzyme 
      indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B 
      and T cell responses driving RA. However, therapeutically targeting IDO2 has been 
      challenging given the lack of small molecules that specifically inhibit IDO2 
      without also affecting the closely related IDO1. In this study, we develop a 
      novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2. 
      Treatment with IDO2-specific mAb alleviated arthritis in two independent 
      preclinical arthritis models, reducing autoreactive T and B cell activation and 
      recapitulating the strong anti-arthritic effect of genetic IDO2 deficiency. 
      Mechanistic investigations identified FcgammaRIIb as necessary for mAb 
      internalization, allowing targeting of an intracellular antigen traditionally 
      considered inaccessible to mAb therapy. Taken together, our results offer 
      preclinical proof of concept for antibody-mediated targeting of IDO2 as a new 
      therapeutic strategy to treat RA and other autoantibody-mediated diseases.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Merlo, Lauren M F
AU  - Merlo LMF
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - Grabler, Samantha
AU  - Grabler S
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - DuHadaway, James B
AU  - DuHadaway JB
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - Pigott, Elizabeth
AU  - Pigott E
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - Manley, Kaylend
AU  - Manley K
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - Prendergast, George C
AU  - Prendergast GC
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA; Department of Pathology, Anatomy and Cell Biology, Sidney Kimmel Medical 
      College, Thomas Jefferson University, 1025 Walnut St. #100, Philadelphia, PA 
      19107, USA; Sidney Kimmel Cancer Center, Thomas Jefferson University, 233 S. 10th 
      St. Suite 1050, Philadelphia, PA 19107, USA.
FAU - Laury-Kleintop, Lisa D
AU  - Laury-Kleintop LD
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA.
FAU - Mandik-Nayak, Laura
AU  - Mandik-Nayak L
AD  - Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, 
      USA. Electronic address: Mandik-NayakL@mlhs.org.
LA  - eng
GR  - R01 AR057847/AR/NIAMS NIH HHS/United States
GR  - R01 CA191191/CA/NCI NIH HHS/United States
GR  - R21 CA159337/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170220
PL  - United States
TA  - Clin Immunol
JT  - Clinical immunology (Orlando, Fla.)
JID - 100883537
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Fcgr2b protein, mouse)
RN  - 0 (IDO2 protein, mouse)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Receptors, IgG)
SB  - IM
CIN - Nat Rev Rheumatol. 2017 Apr;13(4):196-197. PMID: 28275264
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Arthritis, Experimental/*drug therapy/immunology/pathology
MH  - Arthritis, Rheumatoid/chemically induced/*drug therapy/immunology/pathology
MH  - B-Lymphocytes/immunology
MH  - Female
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & 
      inhibitors/genetics/immunology
MH  - Lymph Nodes/cytology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Receptors, IgG/genetics/immunology
MH  - Spleen/cytology
MH  - T-Lymphocytes/immunology
MH  - Tarsal Joints/drug effects/pathology
PMC - PMC5466478
MID - NIHMS856149
OTO - NOTNLM
OT  - Antibody therapy
OT  - B cells
OT  - Experimental arthritis
OT  - IDO
OT  - Murine model
EDAT- 2017/02/23 06:00
MHDA- 2017/08/19 06:00
PMCR- 2018/06/01
CRDT- 2017/02/23 06:00
PHST- 2016/11/15 00:00 [received]
PHST- 2016/12/21 00:00 [revised]
PHST- 2017/01/04 00:00 [accepted]
PHST- 2017/02/23 06:00 [pubmed]
PHST- 2017/08/19 06:00 [medline]
PHST- 2017/02/23 06:00 [entrez]
PHST- 2018/06/01 00:00 [pmc-release]
AID - S1521-6616(16)30605-2 [pii]
AID - 10.1016/j.clim.2017.01.016 [doi]
PST - ppublish
SO  - Clin Immunol. 2017 Jun;179:8-16. doi: 10.1016/j.clim.2017.01.016. Epub 2017 Feb 
      20.