Pavlovic Mirjana, Kats Anna, Cavallo Michelle, Chen Ran, Hartmann James X, Shoenfeld Yehuda
Department of Computer and Electrical Engineering and Computer Science, Florida Atlantic University, Boca Raton, FL 33431, USA.
Autoimmune Dis. 2010 Jul 20;2011:462841. doi: 10.4061/2010/462841.
The discoveries of natural and the development of manufactured highly efficient catalytic antibodies (abzymes) opens the door to many practical applications. One of the most fascinating is the use of such antibodies in human therapy and prevention (vaccination), of cancer, AIDS, autoimmune diseases. A special entity of naturally occurring DNA hydrolytic anti-DNA antibodies is emerging within past decades linked to autoimmune and lymphoproliferative disorders, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), Sjogren Syndrome (SS), B - Chronic lymphocytic leucosis (B-CLL), and Multiple Myeloma (MM). The origin of the antibodies is unknown. The underlying mechanisms of these activities are suggested to be penetration into the living cells and translocation in the nucleus, with recognition of the specific binding sites at particular (ss or ds) DNA. There are controversies in the literature whether hydrolysis is a sequence-specific event. The interplay between anti-DNA antibodies and DNA is not yet elucidated. This molecular "twist" also suggests that anti-DNA antibodies with DNA hydrolytic capacity could be the organism's immune response to a microbial attack, with microbial DNA, or specific genes within microbial DNA sequence, as a target for neutralization. The catalytic antibody-based approach can become a key tool in selective chemotherapeutic strategies.
天然高效催化抗体(抗体酶)的发现以及人工合成高效催化抗体的发展为许多实际应用打开了大门。其中最引人入胜的应用之一是将此类抗体用于人类癌症、艾滋病、自身免疫性疾病的治疗和预防(疫苗接种)。在过去几十年中,一种与自身免疫性和淋巴增殖性疾病相关的天然存在的DNA水解抗DNA抗体特殊实体正在出现,这些疾病包括系统性红斑狼疮(SLE)、多发性硬化症(MS)、干燥综合征(SS)、B细胞慢性淋巴细胞白血病(B-CLL)和多发性骨髓瘤(MM)。这些抗体的起源尚不清楚。这些活性的潜在机制被认为是穿透活细胞并在细胞核内转运,识别特定(单链或双链)DNA上的特定结合位点。文献中对于水解是否是序列特异性事件存在争议。抗DNA抗体与DNA之间的相互作用尚未阐明。这种分子“扭曲”还表明,具有DNA水解能力的抗DNA抗体可能是生物体对微生物攻击的免疫反应,以微生物DNA或微生物DNA序列中的特定基因为中和目标。基于催化抗体的方法可能成为选择性化疗策略的关键工具。