IVIG blocks complement deposition mediated by anti-GM1 antibodies in multifocal motor neuropathy.
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.
Yuki
N
N
Department of Neurology, Niigata National Hospital, Niigata, Japan. micyuki@nus.edu.sg
Watanabe
H
H
Nakajima
T
T
Späth
P J
PJ
D000906:Antibodies / Q000502:physiology*; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies / Q000276:immunology; D001798:Blood Proteins / Q000737:chemistry; D003179:Complement C3b / Q000378:metabolism; D003171:Complement Pathway, Classical / Q000187:drug effects*; D003165:Complement System Proteins / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D005677:G(M1) Ganglioside / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D007167:Immunotherapy; D016472:Motor Neuron Disease / Q000276:immunology* / Q000628:therapy*; D009431:Neural Conduction / Q000187:drug effects; D011901:Ranvier's Nodes / Q000473:pathology
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D001798:Blood Proteins; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; C044203:anti-IgM; D005677:G(M1) Ganglioside; D003179:Complement C3b; D003165:Complement System Proteins