Ghebrehiwet B, Randazzo B P, Kaplan A P
Clin Immunol Immunopathol. 1984 Jul;32(1):101-10. doi: 10.1016/0090-1229(84)90047-3.
It has been observed earlier that the hemolytic complement in diluted sera obtained from patients with hereditary angioedema (HAE) undergoes spontaneous decay when incubated at 37 degrees C. Employing individual serum from patients at different stages of this disease it was demonstrated that this spontaneous loss of hemolytic complement also occurs without dilution and is directly linked to the absence of functional C-1-INA. Incubation of HAE serum resulted in a loss of activity which appears to be dependent upon the concentration of functional C-1-INA. While C-1-INA levels less than 50 micrograms/ml lead to rapid depletion with time, reconstitution of deficient sera with highly purified C-1-INA or of undiluted NHS inhibited spontaneous activation. Furthermore, NHS was rendered susceptible to autoactivation when its C-1-INA was depleted by passage over an anti-C-1-INA Sepharose 4B affinity column in the presence of 10 mM EDTA, indicating that in the absence of functional C-1-INA, C1 undergoes an uninhibited spontaneous autoactivation which leads to the consumption of C4 and C2 but not C3. Consumption of C3 was observed, however, in HAE sera that contained a significant amount of immune complexes. Incubation of HAE sera with highly purified Hageman factor fragment (5 micrograms/ml), or aggregated IgG (2 mg/ml) was found to accelerate the rate of decay when compared to untreated samples while sera from patients under treatment with Danazol or Stanozolol failed to autoactive. These results suggest that, the absence of C-1-INA, may, by itself trigger the dissociation and autoactivation of C1 in the sera of such patients; however, the presence of other complement activators accelerates the reaction. This inherent property of HAE sera, i.e., spontaneous autoactivation at 37 degrees C, may be a useful screening test but direct determination of C-1-INA activity is required to establish the precise diagnosis.
早前已观察到，从遗传性血管性水肿（HAE）患者获得的稀释血清中的溶血补体在37℃孵育时会发生自发衰变。利用处于该疾病不同阶段患者的个体血清证明，这种溶血补体的自发丧失在未稀释时也会发生，并且与功能性C-1-INA的缺失直接相关。HAE血清的孵育导致活性丧失，这似乎取决于功能性C-1-INA的浓度。当C-1-INA水平低于50微克/毫升时，会随着时间快速消耗，用高度纯化的C-1-INA重建缺陷血清或未稀释的正常人类血清（NHS）可抑制自发激活。此外，当NHS的C-1-INA在10 mM EDTA存在下通过抗C-1-INA琼脂糖4B亲和柱而被耗尽时，它会变得易于自激活，这表明在没有功能性C-1-INA的情况下，C1会发生不受抑制的自发自激活，从而导致C4和C2但不是C3的消耗。然而，在含有大量免疫复合物的HAE血清中观察到了C3的消耗。与未处理的样品相比，发现用高度纯化的Hageman因子片段（5微克/毫升）或聚集的IgG（2毫克/毫升）孵育HAE血清会加速衰变速率，而接受达那唑或司坦唑醇治疗的患者的血清则不会自激活。这些结果表明，C-1-INA的缺失本身可能会触发此类患者血清中C1的解离和自激活；然而，其他补体激活剂的存在会加速反应。HAE血清的这种固有特性，即在37℃下自发自激活，可能是一种有用的筛查试验，但需要直接测定C-1-INA活性来建立准确的诊断。
