Bitzan M, Klemt M, Steffens R, Müller-Wiefel D E
Universitäts-Kinderklinik, Hamburg, Germany.
Infection. 1993 May-Jun;21(3):140-5. doi: 10.1007/BF01710530.
Intestinal infection by Escherichia coli O157 and other verotoxin (VT) producing E. coli has been increasingly recognized as an important factor for the causation of classic (enteropathic) hemolytic uremic syndrome (HUS) and hemorrhagic colitis (HC). Toxins most frequently involved are VT1 and VT2. As with other toxin-mediated diseases, administration of immunoglobulin (Ig) may be beneficial. However, little is known about the immune response elicited by the toxin(s), and the prevalence of VT neutralizing antibodies in the healthy population. We studied the capacity of seven Igs and a commercial plasma preparation to neutralize four different VTs (VT1, VT2, VT2c and VT2e). The results were compared with the neutralization titers (NT50%) of normal human serum samples from various age groups. Plasma products and normal sera were separated by protein G affinity chromatography to investigate the factor(s) responsible for VT neutralization. All Igs neutralized VT1 (8 to 96 NT50%). None of them inhibited VT2, VT2c or VT2e effectively. In contrast, none of 40 pediatric, and only one of 20 adult control sera (starting dilution 1:4) neutralized VT1 (25 NT50%). All 60 samples as well as the plasma preparation blocked VT2 (22 to 446 NT50%, median 137), but not VT2c and VT2e. The VT1 neutralizing activity was eluted with the IgG fraction. The VT2 neutralizing activity was not bound by protein G, but was recovered in the IgG-free effluent. In conclusion, therapeutic Igs significantly neutralize VT1, but are largely ineffective against other VTs. In contrast, all control sera inhibited VT2, but rarely VT1.(ABSTRACT TRUNCATED AT 250 WORDS)
大肠杆菌O157及其他产志贺毒素(VT)的大肠杆菌引起的肠道感染,已日益被视为导致典型(肠病性)溶血尿毒综合征(HUS)和出血性结肠炎(HC)的重要因素。最常涉及的毒素是VT1和VT2。与其他毒素介导的疾病一样,给予免疫球蛋白(Ig)可能有益。然而,对于毒素引发的免疫反应以及健康人群中VT中和抗体的流行情况,人们了解甚少。我们研究了七种Ig和一种商业血浆制品中和四种不同VT(VT1、VT2、VT2c和VT2e)的能力。将结果与来自不同年龄组的正常人血清样本的中和效价(NT50%)进行比较。通过蛋白G亲和层析分离血浆制品和正常血清,以研究负责VT中和的因素。所有Ig均能中和VT1(8至96 NT50%)。它们均未有效抑制VT2、VT2c或VT2e。相比之下,40份儿科对照血清中无一能中和VT1(25 NT50%),20份成人对照血清中仅有一份(起始稀释度1:4)能中和VT1。所有60份样本以及血浆制品均能阻断VT2(22至446 NT50%,中位数137),但不能阻断VT2c和VT2e。VT1中和活性随IgG组分洗脱。VT2中和活性不与蛋白G结合,而是在无IgG的流出物中回收。总之,治疗性Ig能显著中和VT1,但对其他VT大多无效。相比之下,所有对照血清均能抑制VT2,但很少能抑制VT1。(摘要截短至250字)