Antibodies against interferon-beta in neuromyelitis optica patients.
Neuromyelitis optica (NMO) is an antibody-mediated autoimmune inflammatory disease of the CNS. A poor response to treatment with recombinant interferon beta (IFN-ß) in NMO patients has been suggested, although the precise mechanisms remain uncertain. We analyzed occurrence and clinical consequences of IFN-neutralizing antibodies (NAbs) in 15 IFN-ß treated NMO-patients from a population-based retrospective case series cohort. NMO patients not treated with IFN-ß acted as a reference group. IFN-ß antibody determinations included binding antibodies (BAbs) measured by immunoassay and NAbs measured by a neutralization bioassay. Antibodies were determined 6-36 months after initiation of IFN-β therapy and NAbs additionally 5-10 years post-therapy. BAbs were detected in 14/15 NMO patients; 6/15 were NAbs-positive (3 at 5-10 years post-therapy) two of those anti-AQP4 antibody-positive; seven of the nine NAbs-negative patients were anti-AQP4 antibody-positive. Eleven patients (three NAbs-positive, eight NAbs-negative) developed cerebral lesions and 12 patients (four NAbs-positive, eight NAbs-negative) spinal cord lesions on magnetic resonance imaging as gadolinium positive lesions or T2-weighted lesions, at significantly higher frequencies than NMO reference group (p<0.009). Exacerbation occurred within 90 days in four and 6-36 months in eight patients. Progression of disease activity in NMO patients occurred during IFN-β treatment, irrespective of IFN-neutralizing antibody status.
Department of Neurology, Vejle Hospital, Odense University Hospital, Denmark; Institute of Molecular Medicine, Odense University Hospital, Denmark; Institute of Regional Health Research, University of Southern Denmark, Odense University Hospital, Denmark. Electronic address: nasgari@health.sdu.dk.
Nasrin
N
Asgari
Institute of Regional Health Research, University of Southern Denmark, Odense University Hospital, Denmark; Odense Patient Data Explorative Network, Odense University Hospital, Denmark.
Kirsten Ohm
KO
Kyvik
Department of Biostatistics, University of Southern Denmark, Odense, Odense University Hospital, Denmark.
Troels
T
Steenstrup
Institute of Regional Health Research, University of Southern Denmark, Odense University Hospital, Denmark; The Multiple Sclerosis Clinic of Southern Jutland (Vejle, Esbjerg, Soenderborg), Department of Neurology, Odense University Hospital, Soenderborg, Denmark.
Egon
E
Stenager
Department of Clinical Immunology, Odense University Hospital, Denmark.
Soeren Thue
ST
Lillevang
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D011159:Population Surveillance / Q000379:methods; D012189:Retrospective Studies; D055815:Young Adult
D001323:Autoantibodies; D016899:Interferon-beta
Anti-aquaporin-4 antibody; Autoimmunity; Interferon-neutralizing antibodies; Magnetic resonance imaging; Multiple sclerosis; Neuromyelitis optica