Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies.
To analyze the in vivo biological effect of anti-interferon beta (IFN-beta) neutralizing antibodies (NABs), blood concentrations of neopterin, beta2microglobulin (Beta2-MG), mRNA-dependent myxovirusresistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (predose) and 24 hours after (postdose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs. The results indicated that predose levels of MxA-mRNA and PKR-mRNA were highly variable [coefficient of variation (CV) > 100%] among patients. A lower inter-individual variability was observed for pre-dose levels of Beta2-MG and neopterin (CVs of 29% and 44%, respectively). Significantly lower pre- and post-dose blood levels of IFN induced markers, except for postdose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB-patients and between patients with high (> 200 t(1/10)) and low ( pound 200 t(1/10)) NAB titers. A significant inverse correlation between NAB titer and pre-dose levels of the above IFN-induced markers was found. In summary, our findings confirm that NABs affect absolute concentrations of IFN-beta induced markers and suggest that such an effect occurs in a titer-dependent manner.
Scagnolari
Carolina
C
Dept. of Experimental Medicine - Virology Section, La Sapienza University, Rome, Italy.
Duda
Petra
P
Bagnato
Francesca
F
De Vito
Gabriella
G
Alberelli
Alessia
A
Lavolpe
Vito
V
Girardi
Enrico
E
Durastanti
Valentina
V
Trojano
Maria
M
Kappos
Ludwig
L
Antonelli
Guido
G
D000328:Adult; D000906:Antibodies / Q000097:blood*; D000937:Antigen-Antibody Reactions; D004185:Disability Evaluation; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016899:Interferon-beta / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D019798:Neopterin / Q000097:blood; D009500:Neutralization Tests / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D001613:beta 2-Microglobulin / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D019798:Neopterin; D016899:Interferon-beta; D019892:eIF-2 Kinase; D019204:GTP-Binding Proteins