LAUSR

&NA; 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. HighlightsBinding of contactin‐1 autoantibodies induces complement deposition and activation.The highest complement deposition can be found associated with the IgG3 subclass of anti‐contactin‐1 auto‐antibodies.IVIG inhibits complement deposition in a dose‐dependent manner, but does not inhibit binding of auto‐antibodies to contactin‐1.