Catalytic diversity of polyclonal RNA-hydrolyzing IgG antibodies from the sera of patients with systemic lupus erythematosus

Catalytic diversity of polyclonal RNA-hydrolyzing IgG antibodies from the sera of patients with systemic lupus erythematosus
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DOI:
10.1016/s0165-2478(02)00006-8
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发表时间:
2002-05-01
期刊:
影响因子:
4.4
通讯作者:
Nevinsky, GA
Nevinsky, GA
中科院分区:
医学3区
文献类型:
--
作者:
Andrievskaya, OA;Buneva, VN;Nevinsky, GA

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在几种自身免疫性疾病患者的血清中已检测到各种催化性抗体或抗体酶,最近我们已经表明,RNA酶活性与系统性红斑狼疮(SLE)患者血清中的IgG和IgM相关,但与正常人血清中的IgG和IgM无关。在这里,我们首次提出了令人信服的证据表明,高度纯化的SLE IgG,其F(ab)片段和分离的L-链催化RNA水解。这些IgG水解RNA的速度比DNA快1 - 3个数量级。这些多克隆IgG的RNA酶活性的酶性质将它们与其他已知的人RNA酶区分开来。它们在核糖寡聚腺苷酸水解中的比活性比RNase A和人血清RNase高2-100倍,并且它们明显更不耐热。此外,它们与不同寡核苷酸底物的比活性、最佳pH值、底物的表观Km值和底物特异性对于不同的患者变化很大。这些发现表明,SLE患者的免疫系统产生了一个多克隆RNA水解I-G库,其可能相对较小或极大。出版社:Elsevier Science B. V.
Various catalytic antibodies or abzymes have been detected in the sera of patients with several autoimmune pathologies, and recently we have shown that RNase activity is associated with IgGs and IgMs from the sera of patients with systemic lupus erythematosus (SLE) but not with those from the sera of normal humans. Here we present for the first time convincing evidence showing that highly purified SLE IgG, its F(ab) Fragments and separated L-chains catalyze RNA hydrolysis. These IgG s hydrolyze RNA about one to three orders of magnitude faster than DNA. The enzymatic properties of the RNase activity of these polyclonal IgGs distinguish them from other known human RNases. Their specific activity in hydrolysis of ribooligoadenylates is 2-100-fold higher than that of RNase A and human serum RNases, and they are markedly more thermolabile. In addition, their specific activities with different oligonucleotide substrates, optimal pHs, apparent Km values for substrates, and substrate specificities varied very much for different patients. These findings show that a pool of polyclonal RNA-hydrolyzing I-G, which may be relatively small or extremely large, is generated by the immune system of SLE patients. 2002 Published by Elsevier Science B.V.