Interferon-beta bioactivity measurement in multiple sclerosis: feasibility for routine clinical practice.
BACKGROUND
Neutralising antibodies (NAb) to interferon beta (IFN beta) are associated with a reduced bioactivity and efficacy of IFN beta in multiple sclerosis (MS). Unclear is how to apply IFN beta bioactivity measurements (quantification of Myxovirus resistance protein A (MxA) mRNA) in clinical practice.


OBJECTIVE
To evaluate value and feasibility of IFN beta bioactivity measurement with a single MxA mRNA measurement for screening and a second measurement before and after IFN beta administration for definite confirmation of IFN beta bioactivity status.


METHODS
In 79 MS patients MxA mRNA expression was determined 4 hours after IFN beta administration. If inadequate, MxA mRNA expression testing was repeated 3 months afterwards, comparing post- and pre injection samples to determine whether IFNb bioactivity was persistently lacking. MxA mRNA expression was compared to NA beta titres, determined by the cytopathic effect assay (CPE).


RESULTS
NAb titres correlated significantly with MxA mRNA expression and MxA mRNA induction. Of all screened patients, only one patient had adequate MxA mRNA expression and high NAb titres simultaneously. Of the biological non-responders at second measurement (21/55), 17 (81%) were high-titre NAb positive, 1 (5%) was low-titre NAb positive and 3 (14%) were NAb negative. Without considering the pre-injection measurement, two more NAb negative patients would have tested negative for IFN beta bioactivity, emphasizing the need of a pre-injection sample.


CONCLUSIONS
Our data suggest that for IFN beta bioactivity screening a single post-injection measurement seems reasonable. However, MxA induction measurement based on both pre- and post-IFN beta injection samples at second measurement is somewhat more precise in determining ultimate IFN beta bioactivity status.
van der Voort
L F
LF
Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands. laura.vandervoort@vumc.nl
Kok
A
A
Visser
A
A
Oudejans
C B M
CB
Caldano
M
M
Gilli
F
F
Bertolotto
A
A
Polman
C H
CH
Killestein
J
J
D000328:Adult; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D016903:Drug Monitoring / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology*; D016899:Interferon-beta / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000378:metabolism; D055815:Young Adult
D000906:Antibodies; D007155:Immunologic Factors; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D016899:Interferon-beta; D019204:GTP-Binding Proteins