Williams R C, Marshall N J, Kilpatrick K, Montano J, Brickell P M, Goodall M, Ealey P A, Shine B, Weetman A P, Craig R K
Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131.
J Clin Invest. 1988 Oct;82(4):1306-12. doi: 10.1172/JCI113731.
From patients with untreated Graves' disease 11 sera showing high cAMP release in the FRTL-5 cell assay were studied for relative proportions of kappa or lambda Ig molecules showing cAMP releasing activity. Immunoabsorption of gamma-globulins was performed using monoclonal murine anti-kappa or anti-lambda antibodies linked to cyanogen bromide-activated sepharose. Specific kappa- or lambda-adsorbed fractions were also eluted from immunoabsorbents using chaotrophic thiocyanate buffers and equilibrated with pH 7.4 low salt buffer by dialysis. Immunoabsorption and elution experiments showed that five Graves' sera contained predominant cAMP-releasing activity within lambda Ig fractions, whereas two Graves' sera showed predominant cAMP-releasing activity in kappa Ig fractions. Four sera showed cAMP release approximately equally divided between kappa and lambda Ig both after immunoabsorption and specific anti-kappa or anti-lambda eluates were studied. C lambda genotypes were examined by Southern blotting and restriction fragment length polymorphism analysis of Eco RI-digested genomic DNA from 158 patients with Graves' disease in parallel with 112 normal controls and 29 patients with autoimmune hypothyroidism. Notable shifts in proportions of 8/8 and 18/18 genotypes were present when Graves' patients were compared with normal controls. Allelic frequencies and ratios of genotype 8 to 18 were significantly different (P less than 0.05) when Graves' patients were compared either to normal controls or to patients with autoimmune hypothyroidism.
对11份来自未经治疗的格雷夫斯病患者、在FRTL-5细胞试验中显示高环磷酸腺苷（cAMP）释放的血清，研究了显示cAMP释放活性的κ或λ免疫球蛋白分子的相对比例。使用与溴化氰活化的琼脂糖偶联的单克隆鼠抗κ或抗λ抗体对γ球蛋白进行免疫吸附。特异性κ或λ吸附组分也使用离液硫氰酸盐缓冲液从免疫吸附剂上洗脱，并通过透析用pH 7.4的低盐缓冲液平衡。免疫吸附和洗脱实验表明，5份格雷夫斯病血清在λ免疫球蛋白组分中含有主要的cAMP释放活性，而2份格雷夫斯病血清在κ免疫球蛋白组分中显示主要的cAMP释放活性。4份血清在免疫吸附后以及研究特异性抗κ或抗λ洗脱液时，显示cAMP释放在κ和λ免疫球蛋白之间大致相等。通过Southern印迹法和对来自158例格雷夫斯病患者、112例正常对照和29例自身免疫性甲状腺功能减退患者的经Eco RI消化的基因组DNA进行限制性片段长度多态性分析，检测了Cλ基因型。当将格雷夫斯病患者与正常对照进行比较时，8/8和18/18基因型的比例出现显著变化。当将格雷夫斯病患者与正常对照或自身免疫性甲状腺功能减退患者进行比较时，等位基因频率以及基因型8与18的比例存在显著差异（P小于0.05）。
