PMID- 20667861
OWN - NLM
STAT- MEDLINE
DCOM- 20110107
LR  - 20171114
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Linking)
VI  - 82
IP  - 1
DP  - 2011 Jan
TI  - IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal 
      motor neuropathy.
PG  - 87-91
LID - 10.1136/jnnp.2010.205856 [doi]
AB  - BACKGROUND: The pathogenesis of multifocal motor neuropathy (MMN) has yet to be 
      established. MMN patients often carry anti-GM1 IgM antibodies, suggesting an 
      autoimmune process involving complement. Intravenous immunoglobulin (IVIG) is the 
      first line treatment, but its action mechanism is unknown. OBJECTIVE: To test 
      whether anti-GM1 IgM antibodies in MMN sera activate complement, inducing and 
      propagating the disease and whether IVIG inhibits complement activation, 
      resulting in clinical improvement. METHODS: Sera with anti-GM1 IgM but not IgG or 
      IgA reactivity were obtained from 13 patients with MMN. We tested whether their 
      anti-GM1 IgM antibodies produced complement component deposits on GM1-coated 
      microtiter plates and whether IVIG blocks such deposition. RESULTS: C1q, C4b, C3b 
      and C5b-9 were deposited on GM1-coated wells. Their depositions were highly 
      correlated with anti-GM1 IgM antibody titre. IVIG reduced the deposition of these 
      complement components dose-dependently. CONCLUSIONS: Anti-GM1 IgM antibodies 
      bound to GM1 and activated complement in vitro. The results together with earlier 
      data from our group suggest that IgM-induced, complement-mediated injury occurs 
      at the nodes of Ranvier in peripheral motor nerves and generates conduction block 
      and muscle weakness. In vitro IVIG inhibited this type of complement activation, 
      suggesting that in vivo, the resulting reduction in membrane attack 
      complex-mediated damage leads to improved muscle strength.
FAU - Yuki, N
AU  - Yuki N
AD  - Department of Neurology, Niigata National Hospital, Niigata, Japan. 
      micyuki@nus.edu.sg
FAU - Watanabe, H
AU  - Watanabe H
FAU - Nakajima, T
AU  - Nakajima T
FAU - Spath, P J
AU  - Spath PJ
LA  - eng
PT  - Journal Article
DEP - 20100728
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Autoantibodies)
RN  - 0 (Blood Proteins)
RN  - 0 (Immunoglobulin M)
RN  - 0 (Immunoglobulins, Intravenous)
RN  - 0 (anti-IgM)
RN  - 37758-47-7 (G(M1) Ganglioside)
RN  - 80295-43-8 (Complement C3b)
RN  - 9007-36-7 (Complement System Proteins)
SB  - IM
MH  - Antibodies/*physiology
MH  - Antibodies, Anti-Idiotypic
MH  - Autoantibodies/immunology
MH  - Blood Proteins/chemistry
MH  - Complement C3b/metabolism
MH  - Complement Pathway, Classical/*drug effects
MH  - Complement System Proteins/metabolism
MH  - Dose-Response Relationship, Immunologic
MH  - G(M1) Ganglioside/*immunology
MH  - Immunoglobulin M/immunology
MH  - Immunoglobulins, Intravenous/*pharmacology
MH  - Immunotherapy
MH  - Motor Neuron Disease/*immunology/*therapy
MH  - Neural Conduction/drug effects
MH  - Ranvier's Nodes/pathology
EDAT- 2010/07/30 06:00
MHDA- 2011/01/08 06:00
CRDT- 2010/07/30 06:00
PHST- 2010/07/30 06:00 [entrez]
PHST- 2010/07/30 06:00 [pubmed]
PHST- 2011/01/08 06:00 [medline]
AID - jnnp.2010.205856 [pii]
AID - 10.1136/jnnp.2010.205856 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2011 Jan;82(1):87-91. doi: 
      10.1136/jnnp.2010.205856. Epub 2010 Jul 28.