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Abstract
Inflammatory neuropathies associated with auto-antibodies against paranodal proteins
like contactin-1 are reported to respond poorly to treatment with intravenous immunoglobulins
(IVIG). A reason might be that IVIG interacts with the complement pathway and these
auto-antibodies often belong to the IgG4 subclass that does not activate complement.
However, some patients do show a response to IVIG, especially at the beginning of
the disease. This corresponds with the finding of coexisting IgG subclasses IgG1,
IgG2 and IgG3. We therefore aimed to investigate complement deposition and activation
by samples of three patients with anti-contactin-1 IgG auto-antibodies of different
subclasses as a potential predictor for response to IVIG. Complement deposition and
activation was measured by cell binding and ELISA based assays, and the effect of
IVIG on complement deposition was assessed by addition of different concentrations
of IVIG. Binding of anti-contactin-1 auto-antibodies of all three patients induced
complement deposition and activation with the strongest effect shown by the serum
of a patient with predominance of IgG3 auto-antibodies. IVIG led to a reduction of
complement deposition in a dose-dependent manner, but did not reduce binding of auto-antibodies
to contactin-1. We conclude that complement deposition may contribute to the pathophysiology
of anti-contactin-1 associated neuropathy, particularly in patients with predominance
of the IgG3 subclass. The proportion of different auto-antibody subclasses may be
a predictor for the response to IVIG in patients with auto-antibodies against paranodal
proteins.