Evidence for classic complement activity in neuromyelitis optica

Sir, – Neuromyelitis optica is a relapsingremitting autoimmune disease associated with the anti-aquaporin-4 antibody (NMOIgG) and complement-mediated perivascular inflammation disease on pathology [1]. Although not specific for NMO, complement deposition is characteristic of the humoral immunopathogenesis. Empiric and laboratory evidence for the involvement of the NMO-IgG as a harmful pathogenic antibody is based on the assumption that the NMOIgG triggers complement activation via the classical complement pathway [2]. Using a human tissue lesion from an NMO patient, we provide further evidence for the pathogenic antibody model by demonstrating the presence of C4d, a complement component regarded as a sign of an antibody-triggered complement response. The autopsy spinal cord tissue was obtained from an NMO-IgG seropositive NMO patient who died shortly after onset of a relapse. Sections were fixed with acetic acid/ methanol and stained with anti-C4d (ALPCO Diagnostics, Salem, NH, USA). Figure 1 shows the intense perivascular staining with C4d in this spinal cord lesion (panels A1, A2, and B) compared to a section without the primary C4d antibody (panels C1 and C2). Also provided is an image of humorally mediated heart transplant rejection staining positive for endothelial C4d indicating antibody-mediated classic complement activity (panel D).