An association between autoreactive antibodies and anti-interferon-beta antibodies in multiple sclerosis.

Approximately 5-25% of interferon-beta (IFN-beta) treated multiple sclerosis (MS) patients develop anti-IFN-beta neutralizing antibodies (NAb) but the patient-specific variables associated with the risk of developing anti-IFN-beta antibodies are poorly understood. Anti-IFN-beta NAb are a subset of anti-IFN-beta binding antibodies (BAb) and all patients with NAb generally have high levels of associated BAb. The purpose of this research was to assess the association between autoreactive antibodies (ARAB) and the risk of developing anti-IFN-beta BAb in MS patients. This was a retrospective study that included consecutive patients diagnosed with clinically definite MS evaluated at our center and considered appropriate for IFN-beta therapy. The patients were tested for various subtypes of antiphospholipid antibodies (APLA) including anti-phosphatidylethanolamine (APE), anti-phosphatidylserine (APS), and anti-cardiolipin (ACA) antibodies, and other ARAB, antinuclear and anti-neutrophilic cytoplasmic antibodies, anti-thyroid peroxidase antibodies (ATA), anti-SS-A and anti-SS-B antibodies. BAb levels were assessed using a commercial binding ELISA assay. A total of 33 patients (mean age: 45.4 years, 85% female) were enrolled; 15 patients were negative and 18 patients were positive for BAb. APLA or ATA were present in 95% (17 of 18 patients) of patients positive for BAb. In comparison, APLA or ATA occurred in only 27% (four of 15 patients) of patients in the BAb negative group. The associations between the occurrence of BAb and the occurrence of high APLA or ATA were significant (chi2 = 13.4, P<0.001in Fisher exact test). The odds ratio for the association was 46.8 (with a 95% confidence interval range of 4.6-475). No significant correlations were found for other ARAB. The presence of autoreactive antibodies, particularly APLA and ATA is associated with increased risk of occurrence of IFN-beta BAb in MS patients on long-term IFN-beta therapy.