The activation of classical and/or lectin complement pathway for the pathogenesis of chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous immune-mediated neuropathy. The activation of the complement system has been implicated in CIDP, but it remains unclear which complement pathway activation is essential for the pathogenesis of CIDP. We therefore examined the deposition and production of several activated complement factors in tissues and serum of CIDP, respectively.

METHODS

We immunohistochemically stained C4d, C3c, and C5b-9 using sural nerve specimens of CIDP and controls. Images were evaluated for the density and fluorescence intensity of complement factor deposition. Serum complement factors (factor H, Ba, sC5b-9, C3, C4 and CH50) were measured in CIDP and in controls. We also investigated clinical data in relation to complement deposition and serum complement factors.

RESULTS

C4d was deposited on the myelin sheaths in all patients with CIDP, with significantly higher density and intensity than in controls. C3c was detected in three of the nine patients with CIDP, while C5b-9 was not detected. Serum levels of sC5b-9 were higher than the normal range in some patients, but no significant differences in serum complement levels were observed between those with CIDP and controls. The C4d density and serum C3 levels were positively correlated with Hughes functional grading scale scores.

CONCLUSIONS

C4d deposition was observed in all patients with CIDP. Few patients showed the activated terminal pathway. The classical and/or lectin pathways are predominantly involved in CIDP pathogenesis. Sural nerve pathology and activated complement factors in the plasma may be useful for selecting therapeutic agents including C2 inhibitors.