Garg N, Weinstock-Guttman B, Bhasi K, Locke J, Ramanathan M
Jacobs Neurological Institute, Buffalo General Hospital, Buffalo, NY, USA.
Mult Scler. 2007 Aug;13(7):895-9. doi: 10.1177/1352458507076968. Epub 2007 Apr 27.
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.
约5%-25%接受β-干扰素（IFN-β）治疗的多发性硬化症（MS）患者会产生抗IFN-β中和抗体（NAb），但与产生抗IFN-β抗体风险相关的患者特异性变量尚不清楚。抗IFN-β NAb是抗IFN-β结合抗体（BAb）的一个子集，所有有NAb的患者通常都有高水平的相关BAb。本研究的目的是评估自身反应性抗体（ARAB）与MS患者产生抗IFN-β BAb风险之间的关联。这是一项回顾性研究，纳入了在我们中心接受评估且被认为适合IFN-β治疗的连续诊断为临床确诊MS的患者。对患者进行了多种抗磷脂抗体（APLA）亚型检测，包括抗磷脂酰乙醇胺（APE）、抗磷脂酰丝氨酸（APS）和抗心磷脂（ACA）抗体，以及其他ARAB、抗核抗体和抗中性粒细胞胞浆抗体、抗甲状腺过氧化物酶抗体（ATA）、抗SS-A和抗SS-B抗体。使用商业结合ELISA检测法评估BAb水平。共纳入33例患者（平均年龄：45.4岁，85%为女性）；15例患者BAb为阴性，18例患者BAb为阳性。BAb阳性患者中95%（18例中的17例）存在APLA或ATA。相比之下，BAb阴性组中仅27%（15例中的4例）患者出现APLA或ATA。BAb的出现与高APLA或ATA的出现之间的关联具有显著性（Fisher精确检验中χ2 = 13.4，P<0.001）。关联的比值比为46.8（95%置信区间范围为4.6-475）。未发现其他ARAB有显著相关性。自身反应性抗体，尤其是APLA和ATA的存在与长期接受IFN-β治疗的MS患者产生IFN-β BAb的风险增加相关。
