Myxovirus resistance protein A in interferon-β therapy in patients with multiple sclerosis and treatment effectiveness monitoring algorithm
Abstract
Introduction: Interferon-beta IFN beta is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is considered to be an IFN beta bioactivity marker.
Responsiveness to the IFN beta treatment may be reduced by neutralizing antibodies (NAbs). Material and methods: We investigated the presence of NAbs and mRNA MxA expression in a group of patients who had started IFN beta treatment. mRNA MxA was measured with real-time PCR every three months.
MxA induction was performed in patients in whom continuous decline was detected. NAbs were determined using the cytopathic effect method every six months.
Patients were regularly observed clinically and with MRI. Results: 119 patients were included, 99 completed the observation period of 24 months.
NAbs positivity was observed in 17 patients, mostly in month 12 and 18. NAbs positivity was permanent in ten patients (10%).
Nabs titre of 20-100 TRU/ml was associated with a decline in MxA levels under the cut-off in 85% of cases, and in all patients when Nabs titre exceeded 100 TRU/ml. Permanent MxA decline was seen in 19 patients - in all 10 patients with permanent NAbs positivity, in three patients with transitional NAbs positivity and in six patients without NAbs.
MxA induction was insufficient in all permanent NAbs positive patients and in two patients with isolated MxA decrease and without NAbs. MxA decrease preceded NAbs positivity in 40% of cases.
Conclusion: MxA becomes the main laboratory marker of IFN beta efficacy as it can indicate patients at risk of IFN beta efficacy loss, even in situations when patients produce NAbs. MxA induction is necessary to verify IFN beta efficacy.