Pharmacodynamics of interferon beta in multiple sclerosis patients with or without serum neutralizing antibodies

Scagnolari C, Duda P, Bagnato F, De Vito G, Alberelli A, Lavolpe V, Girardi E, Durastanti V, Trojano M, Kappos L, Antonelli G.

Dept. of Experimental Medicine - Virology Section, "La Sapienza" University, Rome, Italy.

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 myxovirus-resistant protein A (MxA) and dsRNA-dependent protein kinase (PKR) were measured before (pre-dose) and 24 hours after (post-dose) IFN-beta administration in 49 patients with multiple sclerosis (MS) with (n = 25) and without (n = 24) NABs.The results indicated that pre-dose 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 post-dose PKR-mRNA (p = 0.09), were seen in NAB+ compared with NAB- patients and between patients with high (> 200 t(1/10)) and low (</= 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.

PMID: 17420930 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17420930&itool=pubmed_DocSum