Study of binding and neutralising antibodies to interferon-beta in two groups of relapsing-remitting multiple sclerosis patients.
Interferon (IFN)-beta is generally considered an effective treatment for multiple sclerosis (MS); however, some patients do not respond to this therapy, possibly due to the production of neutralising antibodies (NAB) which can prevent the biological effect of IFN-beta. We compared the two types of IFN-beta, the glycosylated IFN-beta1a and the non-glycosylated IFN-beta1b, as their chemical differences may entail differing immunogenic capacities. We studied 22 relapsing-remitting MS patients treated with IFN-beta1a and 31 treated with IFN-beta1b for 1 year, using the same assay and criteria, to compare the two types of IFN-beta in their ability to induce binding and neutralising antibodies and examined the correlation of the findings with the clinical data. Binding antibodies to IFN-beta1a and IFN-beta1b were determined by enzyme-linked immunosorbent assay. A bioassay was used to detect and quantify the NABs to IFN-beta, measuring the capacity of NABs to block the antiviral resistance induced by IFNs. Binding antibodies were found in 32 % of those treated with IFN-beta1a and in 52 % of those treated with IFN-beta1b; NABs were found in 14% and 24 %, respectively. Both groups showed a significant decrease in relapse rate during the first year of treatment. These results demonstrate that the IFN-beta1b molecule is more immunogenic than the IFN-beta1a molecule. This may be due to the non-glycosylated, chemical structure of the former, which can produce aggregates and enhance antibody production. No association was found between the presence of NABs and the clinical status of the patients.
Fernández
O
O
Neurology Service, Carlos Haya Hospital, Málaga, Spain. ofernand@hch.sas.cica.es
Mayorga
C
C
Luque
G
G
Guerrero
M
M
Guerrero
R
R
Leyva
L
L
León
A
A
Blanca
M
M
D000328:Adult; D000917:Antibody Formation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006031:Glycosylation; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000494:pharmacology*; D016899:Interferon-beta / Q000276:immunology* / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D011446:Prospective Studies; D012008:Recurrence
D007155:Immunologic Factors; D016899:Interferon-beta