Interferon inhibitory activity in patients with multiple sclerosis.
BACKGROUND
Interferon inhibitory activity (IIA) is a logical candidate for explaining neutralizing antibody-negative partial responsiveness to interferon beta in multiple sclerosis (MS), but its role has not been evaluated.


OBJECTIVE
To investigate the role of IIA and soluble interferon-alpha/beta receptor (sIFNR) in determining response of patients with MS to interferon beta therapy.


METHODS
Parallel-group, open-label study.


METHODS
Baird Multiple Sclerosis Center, Buffalo, NY. Patients Blood was obtained before and 24 hours after injection of interferon beta-1a from 38 anti-interferon beta neutralizing antibody-negative patients with relapsing-remitting MS and 16 untreated healthy controls. On the basis of clinical parameters of response to interferon beta therapy, the patients were divided into stable or good-responder (n = 20) and active or partial-responder (n = 18) groups.


METHODS
Quantitative analyses of magnetic resonance imaging were obtained; the IIA and sIFNR levels were measured using bioassay and enzyme-linked immunosorbent assay, respectively.


RESULTS
The IIA and sIFNR levels were elevated in MS patients compared with controls (P<.001). The IIA levels were higher in active or partial responders compared with stable or good responders (P<.001); the sIFNR levels were not different between groups. The Extended Disability Status Score and T2 lesion volumes were higher in the active or partial-responder group compared with the stable or good-responder group. Interferon beta-1a did not have short-term effects on the IIA and sIFNR levels. In univariate general linear model and stepwise regression analyses, IIA levels were associated with T2 lesion volume.


CONCLUSIONS
The levels of IIA are associated with increased MS disease activity and with responsiveness to interferon beta therapy in anti-interferon beta neutralizing antibody-negative MS patients.
Chadha
Kailash
K
Department of Cell and Molecular Biology, Roswell Park Cancer Institute, Jacobs Neurological Institute, , Buffalo, New York 14263, USA. Kailash.Chadha@RoswellPark.org
Weinstock-Guttman
Bianca
B
Zivadinov
Robert
R
Bhasi
Kavitha
K
Muhitch
Jason
J
Feichter
Joan
J
Tamaño-Blanco
Miriam
M
Abdelrahman
Nadir
N
Ambrus
Julian
J
Munschauer
Frederick
F
Ramanathan
Murali
M
D000328:Adult; D000906:Antibodies / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000276:immunology / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D017471:Receptors, Interferon / Q000037:antagonists & inhibitors* / Q000097:blood; D001613:beta 2-Microglobulin / Q000097:blood
D000906:Antibodies; D017471:Receptors, Interferon; D001613:beta 2-Microglobulin; D016899:Interferon-beta; D000068556:Interferon beta-1a