Beneficial effect of interferon-β 1b treatment in patients with relapsing–remitting multiple sclerosis is associated with an increase in serum levels of soluble HLA-I molecules during the first 3 months of therapy

Abstract

It has recently become clear that interferon-β (IFN-β) treatment is effective in ameliorating relapsing–remitting multiple sclerosis (RRMS) through an as yet unidentified mechanism. As there is no recognisable biological indicator to predict responsiveness to IFN-β treatment, we have investigated fluctuations in serum sHLA-I levels in MS patients undergoing IFN-β 1b therapy. Serum sHLA-I concentrations measured by enzyme-linked immunosorbent assay (ELISA) were assessed at baseline and, longitudinally, over a period of 18 months after the start of treatment in 29 RRMS patients grouped as responders and nonresponders according to their clinical response to IFN-β 1b therapy. Thirty-nine healthy volunteers served as controls. Serum sHLA-I concentrations were significantly higher ( p<0.001) in pretreated RRMS patients than in healthy donors. In MS patients, changes in mean serum levels of sHLA-I from baseline showed a temporal pattern characterized by a strong increase in the first trimester of treatment, a return toward basal values in the following 6 months, a slight decline at 12th and 15th months and a further moderate increase at the 18th month. Mean serum sHLA-I levels were significantly more elevated in responders than in nonresponders at the first ( p<0.02), second ( p<0.01), and at third ( p<0.02) months after the beginning of treatment and significantly lower ( p<0.01) at the time of relapses in comparison to baseline values. Overall, these results seem to indicate that IFN-β 1b can modulate fluctuations in serum sHLA-I levels and argue in favour of a potential role for serum levels of sHLA-I as a sensitive marker to monitor response to IFN-β treatment in MS.