Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing activity and cross-reactivity with three different preparations.
The presence and titer of neutralizing antibodies (NABs) was evaluated by an antiviral biological assay in 387 samples of 111 multiple sclerosis (MS) patients treated with one of the three commercial preparations of interferon beta (IFNbeta). Fifty NAB positive samples were found in 19 patients: 11 treated with IFNbeta-1b (Betaferon(R)) and eight with IFNbeta-1a (five with Avonex(R) and three with Rebif(R)). All the 38 NABs+ samples of patients treated with IFNbeta-1b cross-reacted with IFNbeta-1a of both commercial types. The median level of neutralizing units (NUs) of the sera was higher when tested against IFNbeta-1a than against IFNbeta-1b (p=0.000 vs. Avonexr(R) and p=0.003 vs. Rebif(R)). In line with these data, the NABs+ sera of patients treated with IFNbeta-1a cross-reacted with IFNbeta-1b and the level of NUs were lower when tested against IFNbeta-1b than against IFNbeta-1a (p=0.003). The different amount of NUs against IFNbeta types 1a and 1b could be due to the presence of aggregates in the IFNbeta-1b preparation. The different levels of cross-reactivity of NABs could reduce the bioavailability and therapeutic efficacy of IFNbeta in NABs+ patients switching from IFNbeta-1b to IFNbeta-1a.
Divisione Universitaria di Neurologia, Ospedale San Luigi, Regione Gonzole 10, 10043 Orbassano (TO), Italy. nsglb@tin.it
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A
Bertolotto
S
S
Malucchi
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E
Milano
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Castello
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Capobianco
R
R
Mutani
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000627:therapeutic use; D000906:Antibodies / Q000378:metabolism*; D003429:Cross Reactions; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D006801:Humans; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000276:immunology* / Q000628:therapy; D009500:Neutralization Tests; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000906:Antibodies; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a