NEUTRALIZING AND BINDING ANTI-INTERFERON-BETA-1B (IFN-BETA-1B) ANTIBODIES DURING IFN-BETA-1B TREATMENT OF MULTIPLE-SCLEROSIS

Interferon-beta-lb (IFN-beta-lb) is on immunomodulatory therapy of mul tiple sclerosis (MS), reducing the numbers and severity of exacerbatio ns and the total lesion load measured by magnetic resonance imaging of the brain. The benefits of IFN-beta-lb could be hampered by the devel opment of neutralising antibodies against the compound. Our results co nfirmed earlier studies, showing that 42% of MS patients treated with IFN-beta-lb for more than 3 months had developed neutralising antibodi es. The occurrence of binding anti-IFN-beta-lb antibodies, presently n ot believed to impede the clinical efficacy of IFN-beta-lb, were demon strated by on immunoassay in some patients already after 1 month of tr eatment and in 78% after 3 months. The development of binding antibodi es seemed to be on early phenomenon, preceding the appearance of neutr alising antibodies. Antibodies crossreacting with IFN-beta-la and natu ral IFN-beta were also found in a majority of IFN-beta-lb treated Pati ents with high titres of binding antibodies. Employing a solid-phase e nzyme-linked immunospot (ELISPOT) assay 68% of MS patients treated wit h IFN-beta-lb for 1-23 months had elevated numbers of anti-IFN-beta-lb -antibody secreting cells in blood, compared to 18% of untreated MS pa tients and 20% among patients with other neurological diseases. Thus, our findings confirm that IFN-beta-lb is immunogenic in MS patients. H igh levels of anti-IFN-beta-lb antibody secreting cells were, however, also found in two untreated control patients with inflammatory diseas es, suggesting that anti-IFN-beta-lb antibodies might also occur spont aneously.