单克隆抗体可防肺结核感染

英国一研究小组在最近一期出版的《免疫学杂志》上发表论文称，他们开发出一种单克隆抗体，经实验模型验证，该抗体与干扰素结合使用，可有效对抗肺结核感染。研究人员认为，这一成果有助于科学家开发出新的结核病治疗手段。

该研究小组由英国邓迪大学、伦敦国王大学以及伦敦大学圣乔治学院的研究人员组成。他们开发的这种单克隆抗体是一种A类免疫球蛋白（lgA），属于同 质性抗体，可识别结核杆菌。它通过绑定结核杆菌细菌，触发人体免疫反应，从而防止该细菌生长蔓延。论文称，尽管单克隆抗体已被广泛用于癌症和炎症性疾病的 治疗，但这还是第一次研究表明，它可以用来治疗结核病。

免疫球蛋白是人体内十分重要的免疫效应分子，因结构不同可分为IgA、IgD、IgE、IgG和IgM五大类。研究人员认为，A类免疫球蛋白所具有 的特性使其更易对抗结核病菌。尽管实际临床应用之前还要进行许多研究，但这一发现使科学家距离开发出新的结核病治疗方法更近了一步。

肺结核是目前人类面临的重大公共健康问题之一，全球每年有大约200万人死于该疾病，英国2010年的肺结核病例数则创下了10年来的新高。虽然由 于多种抗生素和预防药物的产生使肺结核病例在世界范围内曾一度迅速减少，但随之而来，肺结核菌株的多重耐药性也越来越明显，研制出新方法来预防和控制该种 疾病显得极为迫切。

原文出处：

The Journal of Immunology  doi: 10.4049/jimmunol.1003189

A Novel Human IgA Monoclonal Antibody Protects against Tuberculosis

Sucharitha Balu*, Rajko Reljic?, Melanie J. Lewis?, Richard J. Pleass§?, Richard McIntosh?, Cees van Kooten‖, Marjolein van Egmond#, Stephen Challacombe*, Jenny M. Woof? and Juraj Ivanyi*

Abs have been shown to be protective in passive immunotherapy of tuberculous infection using mouse experimental models. In this study, we report on the properties of a novel human IgA1, constructed using a single-chain variable fragment clone (2E9), selected from an Ab phage library. The purified Ab monomer revealed high binding affinities for the mycobacterial α-crystallin Ag and for the human FcαRI (CD89) IgA receptor. Intranasal inoculations with 2E9IgA1 and recombinant mouse IFN-γ significantly inhibited pulmonary H37Rv infection in mice transgenic for human CD89 but not in CD89-negative littermate controls, suggesting that binding to CD89 was necessary for the IgA-imparted passive protection. 2E9IgA1 added to human whole-blood or monocyte cultures inhibited luciferase-tagged H37Rv infection although not for all tested blood donors. Inhibition by 2E9IgA1 was synergistic with human rIFN-γ in cultures of purified human monocytes but not in whole-blood cultures. The demonstration of the mandatory role of FcαRI (CD89) for human IgA-mediated protection is important for understanding of the mechanisms involved and also for translation of this approach toward development of passive immunotherapy of tuberculosis.