Williams J M, Gorevic P D, Looney R J, Abraham G N
Department of Medicine, University of Rochester Medical Center, NY 14642.
Immunology. 1987 Dec;62(4):529-36.
Previous studies have demonstrated that the IgM monoclonal anti-IgG autoantibodies (AGAs) characteristic of essential mixed cryoglobulinaemia (EMC) display preferential use of kappa light chains of the VKiiib sub-subgroup. In order to gain insights as to the possible basis for this V region selection, IgM-VKiiib immunoglobulin was affinity purified from normal human serum, analysed by dissociating two-dimensional gel electrophoresis and compared to the two-dimensional gel patterns of IgM-VKiiib anti-IgG autoantibodies (AGAs) from patients with essential mixed cryoglobulinaemia (EMC). The results suggest that only part of the available VKiiib light chain repertoire is selected by EMC AGAs. When AGAs from EMC, rheumatoid arthritis (RA) and primary Sjögren's syndrome (SS) patients were analysed by ELISA, it was found that the association of the VKiiib light chains with anti-IgG autoantibodies differed significantly among the three diseases. In fact, in RA there appeared to be a negative selection against the use of VKiiib in AGAs. Clearly, the VKiiib determinant is not required for anti-IgG autoreactivity. The possibility emerges, therefore, that the genesis and perpetuation of AGA synthesis in these diseases may follow quite different pathways.
以往的研究表明，原发性混合性冷球蛋白血症（EMC）所特有的IgM单克隆抗IgG自身抗体（AGA）优先使用VKiiib亚亚组的κ轻链。为了深入了解这种V区选择的可能基础，从正常人血清中亲和纯化IgM-VKiiib免疫球蛋白，通过解离二维凝胶电泳进行分析，并与原发性混合性冷球蛋白血症（EMC）患者的IgM-VKiiib抗IgG自身抗体（AGA）的二维凝胶图谱进行比较。结果表明，EMC的AGA仅选择了可用的VKiiib轻链库的一部分。当通过ELISA分析来自EMC、类风湿性关节炎（RA）和原发性干燥综合征（SS）患者的AGA时，发现VKiiib轻链与抗IgG自身抗体的关联在这三种疾病中存在显著差异。事实上，在RA中，AGA似乎对VKiiib的使用存在负选择。显然，抗IgG自身反应性并不需要VKiiib决定簇。因此，这些疾病中AGA合成的发生和持续可能遵循截然不同的途径。
