Neutralizing antibodies reduce MxA protein induction in interferon-beta-1a-treated MS patients.
BACKGROUND
Neutralizing antibodies (NAb) during interferon-beta (IFNbeta) treatment of MS are associated with reduced clinical and MR efficacy. NAb inhibit the IFN- inducible MxA gene expression and neutralize the capability of IFNbeta to inhibit virus growth in vitro. Presently, there is no clear concept of the biologic importance of IFNbeta antibodies; most of the tests applied for the detection of NAb in previous publications are not widely available, and the results are not fully comparable.


METHODS
A 1-year prospective study of the development of binding antibodies (BAb) and NAb and their relationship to IFN-inducible MxA protein levels in peripheral blood leukocytes in 20 IFNbeta-1a-treated patients with relapsing-remitting MS was conducted.


RESULTS
In seven of nine NAb-positive patients, IFNbeta-1a was unable to induce MxA protein. BAb were detected in 11 patients, and they preceded or paralleled the development of NAb in all the patients. The titer of NAb correlated positively with BAb titer and negatively with MxA expression level. There was also a weaker but clear correlation between BAb titers and MxA levels.


CONCLUSIONS
NAb, in most but not all cases, inhibited the in vivo function of IFNbeta. Analysis of MxA protein in lymphocytes together with analysis of NAb is a promising marker for evaluating the biologic effects of IFNbeta treatment in MS patients.
Vallittu
A-M
AM
Department of Virology, Turku Immunology Centre and University of Turku, Finland. anna-maija.vallittu@utu.fi
Halminen
M
M
Peltoniemi
J
J
Ilonen
J
J
Julkunen
I
I
Salmi
A
A
Erälinna
J-P
JP
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D064547:Myxovirus Resistance Proteins; D011446:Prospective Studies; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors*; D018709:Statistics, Nonparametric
D000276:Adjuvants, Immunologic; D000906:Antibodies; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D016899:Interferon-beta; D019204:GTP-Binding Proteins; D000068556:Interferon beta-1a