Lawrence N, Oger J, Aziz T, Palace J, Vincent A
Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
J Neurol Neurosurg Psychiatry. 2003 Sep;74(9):1236-9. doi: 10.1136/jnnp.74.9.1236.
Some multiple sclerosis (MS) patients treated with interferon beta (IFN beta) develop antibodies to the drug. Neutralising antibody (NAB) assays for IFN beta are expensive and the clinical relevance of the results has been debated.
To establish a cheap, sensitive, and reliable assay for antibodies to (125)I-IFN beta, and to correlate levels of antibodies with clinical response to IFN beta treatment.
We established a radioimmunoprecipitation assay (RIPA) using (125)I-IFN beta. We tested NAB positive sera, healthy control sera, and serial samples of 33 IFN beta-1b treated MS patients from the Vancouver cohort of the Berlex pivotal trial who had a high incidence of NABs.
We found that the RIPA was highly sensitive for the detection of antibodies to IFN beta-1a and -1b, and that there was a strong correlation between reactivity of NAB positive sera for (125)I-IFN beta-1b and for (125)I-IFN beta-1a. The RIPA was more sensitive and consistent than the NAB. Moreover, there was a trend towards poorer MRI outcomes in RIPA positive patients, but not in NAB-positive patients.
The RIPA assay is sensitive and easy to perform. It should be of value in assessing the clinical impact of IFN beta antibodies, and its use could help target expensive INF beta treatments to those who will respond best.
一些接受β-干扰素(IFNβ)治疗的多发性硬化症(MS)患者会产生针对该药物的抗体。用于检测IFNβ的中和抗体(NAB)检测方法昂贵,且检测结果的临床相关性一直存在争议。
建立一种廉价、灵敏且可靠的针对(125)I-IFNβ抗体的检测方法,并将抗体水平与IFNβ治疗的临床反应相关联。
我们使用(125)I-IFNβ建立了一种放射免疫沉淀测定法(RIPA)。我们检测了NAB阳性血清、健康对照血清,以及来自Berlex关键试验温哥华队列的33例接受IFNβ-1b治疗的MS患者的系列样本,这些患者中NAB的发生率很高。
我们发现RIPA对检测IFNβ-1a和-1b的抗体具有高度敏感性,并且NAB阳性血清对(125)I-IFNβ-1b和(125)I-IFNβ-1a的反应性之间存在很强的相关性。RIPA比NAB更灵敏且更稳定。此外,RIPA阳性患者的MRI结果有变差的趋势,但NAB阳性患者则没有。
RIPA检测灵敏且易于操作。它在评估IFNβ抗体的临床影响方面应该具有价值,其应用有助于将昂贵的IFNβ治疗靶向那些反应最佳的患者。