PMID- 34177770
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210629
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 12
DP  - 2021
TI  - Anti-Neurofascin 155 Antibody-Positive Chronic Inflammatory Demyelinating 
      Polyneuropathy/Combined Central and Peripheral Demyelination: Strategies for 
      Diagnosis and Treatment Based on the Disease Mechanism.
PG  - 665136
LID - 10.3389/fneur.2021.665136 [doi]
LID - 665136
AB  - Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated 
      demyelinating disease of the peripheral nervous system (PNS). A small number of 
      CIDP patients harbors autoantibodies against nodal/paranodal proteins, such as 
      neurofascin 155 (NF155), contactin 1, and contactin-associated protein 1. In most 
      cases, the predominant immunoglobulin (IgG) subclass is IgG4. Node/paranode 
      antibody-positive CIDP demonstrates distinct features compared with 
      antibody-negative CIDP, including a poor response to intravenous immunoglobulin. 
      The neuropathology of biopsied sural nerve shows Schwann cell terminal loop 
      detachment from axons without macrophage infiltration or inflammation. This is 
      partly attributable to IgG4, which blocks protein-protein interactions without 
      inducing inflammation. Anti-NF155 antibody-positive (NF155(+)) CIDP is unique 
      because of the high frequency of subclinical demyelinating lesions in the central 
      nervous system (CNS). This is probably because NF155 coexists in the PNS and CNS. 
      Such cases showing demyelinating lesions in both the CNS and PNS are now termed 
      combined central and peripheral demyelination (CCPD). NF155(+) CIDP/CCPD commonly 
      presents hypertrophy of spinal nerve roots and cranial nerves, such as trigeminal 
      and oculomotor nerves, and extremely high levels of cerebrospinal fluid (CSF) 
      protein, which indicates nerve root inflammation. In the CSF, the CXCL8/IL8, 
      IL13, TNFalpha, CCL11/eotaxin, CCL2/MCP1, and IFNgamma levels are significantly higher 
      and the IL1beta, IL1ra, and GCSF levels are significantly lower in NF155(+) CIDP 
      than in non-inflammatory neurological diseases. Even compared with anti-NF155 
      antibody-negative (NF155(-)) CIDP, the CXCL8/IL8 and IL13 levels are 
      significantly higher and the IL1beta and IL1ra levels are significantly lower than 
      those in NF155(+) CIDP. Canonical discriminant analysis revealed NF155(+) and 
      NF155(-) CIDP to be separable with IL4, IL10, and IL13, the three most 
      significant discriminators, all of which are required for IgG4 class switching. 
      Therefore, upregulation of both Th2 and Th1 cytokines and downregulation of 
      macrophage-related cytokines are characteristic of NF155(+) CIDP, which explains 
      spinal root inflammation and the lack of macrophage infiltration in the sural 
      nerves. All Japanese patients with NF155(+) CIDP/CCPD have one of two specific 
      human leukocyte antigen (HLA) haplotypes, which results in a significantly higher 
      prevalence of HLA-DRB1 (*) 15:01-DQB1 (*) 06:02 compared with healthy Japanese 
      controls. This indicates an involvement of specific HLA class II molecules and 
      relevant T cells in addition to IgG4 anti-NF155 antibodies in the mechanism 
      underlying IgG4 NF155(+) CIDP/CCPD.
CI  - Copyright (c) 2021 Kira.
FAU - Kira, Jun-Ichi
AU  - Kira JI
AD  - Translational Neuroscience Center, Graduate School of Medicine, and School of 
      Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka, 
      Japan.
AD  - Department of Neurology, Brain and Nerve Center, Fukuoka Central Hospital, 
      International University of Health and Welfare, Fukuoka, Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210610
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC8222570
OTO - NOTNLM
OT  - IgG4
OT  - chronic inflammatory demyelinating polyneuropathy
OT  - combined central and peripheral demyelination
OT  - neurofascin 155
OT  - node of Ranvier
COIS- J-iK received research funds from Dainippon Sumitomo Pharma, Daiichi Sankyo, 
      Mitsubishi Tanabe Pharma, and Kyowa Kensetsukougyo, and consultancy fees, 
      speaking fees and/or honoraria from Novartis Pharma, Mitsubishi Tanabe Pharma, 
      CSL Behring, Biogen Japan, Teijin Health Care, the Takeda Pharmaceutical Company, 
      Kyowa Kirin, Ono Pharmaceutical Co. Ltd., Alexion Pharmaceuticals Inc., Tsumura, 
      Ricoh, EMC, and Eisai.
EDAT- 2021/06/29 06:00
MHDA- 2021/06/29 06:01
PMCR- 2021/06/10
CRDT- 2021/06/28 05:55
PHST- 2021/02/07 00:00 [received]
PHST- 2021/04/06 00:00 [accepted]
PHST- 2021/06/28 05:55 [entrez]
PHST- 2021/06/29 06:00 [pubmed]
PHST- 2021/06/29 06:01 [medline]
PHST- 2021/06/10 00:00 [pmc-release]
AID - 10.3389/fneur.2021.665136 [doi]
PST - epublish
SO  - Front Neurol. 2021 Jun 10;12:665136. doi: 10.3389/fneur.2021.665136. eCollection 
      2021.