Cytotoxic effect of neuromyelitis optica antibody (NMO-IgG) to astrocytes: an in vitro study.
NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) that binds selectively to aquaporin-4 (AQ4), an astrocytic water channel. The normal distribution of AQP4 coincides with the sites of immunoglobulin and complement deposits in lesions found in autopsy studies. The underlying mechanisms of cytotoxicity by NMO-IgG on astrocytes are not well known. In this study we show that serum samples from seropositive NMO patients (21) induce a higher rate of cell death compared with sera from seronegative NMO (16), relapsing-remitting MS (20) patients, and healthy controls (24) on primary cultures of astrocytes. Similar results were obtained by two different techniques: lactate dehydrogenase release and tetrazolium-based viability assay. Cell death was only observed in the presence of active complement. The complement-dependent cytotoxicity was not accompanied by caspase-3/7 activation or increase in the percentage of apoptotic cells. Our data show that NMO-IgG induces a complement-dependent cytotoxicity of astrocytes in vitro, and suggest that a mechanism of cellular death by necrosis might be implicated in the pathophysiology of NMO.
Sabater
Lidia
L
Service of Neurology, Hospital Clinic, Universitat de Barcelona and Institut d'Investigació Biomèdica August Pi i Sunyer, Spain.
Giralt
Albert
A
Boronat
Anna
A
Hankiewicz
Karolina
K
Blanco
Yolanda
Y
Llufriu
Sara
S
Alberch
Jordi
J
Graus
Francesc
F
Saiz
Albert
A
D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D001253:Astrocytes / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
D000906:Antibodies; D007074:Immunoglobulin G; D003165:Complement System Proteins