Svenson M, Hansen M B, Ross C, Diamant M, Rieneck K, Nielsen H, Bendtzen K
Lab Med Immunol, and Lab Clin IFN research, Institute for Inflammation Research, and Dept Clin Immunol, Rigshospitalet University Hospital, Copenhagen, Denmark.
Blood. 1998 Mar 15;91(6):2054-61.
Pharmaceutical preparations of normal human immunoglobulin (IgG) are known to contain high-avidity and neutralizing antibodies (Ab) to the cytokines interleukin (IL)-1alpha, IL-6, and interferon (IFN)alpha. To test for other cytokine Ab, 23 batches of IgG were tested for saturable binding to eight 125I-labeled recombinant cytokines. All batches bound granulocyte-macrophage colony-stimulating factor (GM-CSF) with high avidity (Kav approximately 10 pmol/L) and capacities of up to 5 mumol GM-CSF/mol IgG. Only 1 of 15 batches bound IL-5, also with high avidity, whereas 13 of 15 batches bound to IL-10 but with lower capacities and avidities. None of the IgG preparations bound IL-1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, or G-CSF. Cross-binding and absorption analyses revealed identical or slightly stronger binding of recombinant GM-CSF, IL-5, and IL-10 than their native counterparts. GM-CSF-IgG complexes did not bind to cellular GM-CSF receptors, but Fc-dependent binding occurred to blood polymorphonuclear cells. Increased binding of GM-CSF to patient sera correlated positively with the binding capacities of infused IgG preparations. Patient and normal sera did not interfere with the binding of Ab to GM-CSF. From these and previous experiments, we conclude that pools of normal human IgG contain variable amounts of specific and high-avidity Ab to some cytokines, and that Ab to GM-CSF constitute a dominant anti-cytokine activity in these preparations. These Ab are available for reaction in vivo following IgG therapy.
已知正常人免疫球蛋白（IgG）制剂含有针对细胞因子白细胞介素（IL）-1α、IL-6和干扰素（IFN）α的高亲和力中和抗体（Ab）。为检测其他细胞因子Ab，对23批IgG进行了检测，以确定其与8种125I标记的重组细胞因子的可饱和结合情况。所有批次的IgG均以高亲和力（亲和常数Kav约为10 pmol/L）结合粒细胞-巨噬细胞集落刺激因子（GM-CSF），结合能力高达5 μmol GM-CSF/mol IgG。15批中有1批也以高亲和力结合IL-5，而15批中有13批结合IL-10，但结合能力和亲和力较低。没有一种IgG制剂结合IL-1受体拮抗剂（IL-1ra）、IL-2、IL-3、IL-4或粒细胞集落刺激因子（G-CSF）。交叉结合和吸收分析显示，重组GM-CSF、IL-5和IL-10的结合与其天然对应物相同或略强。GM-CSF-IgG复合物不与细胞GM-CSF受体结合，但可通过Fc依赖性结合作用于血液中的多形核细胞。GM-CSF与患者血清结合增加与输注的IgG制剂的结合能力呈正相关。患者血清和正常血清均不干扰Ab与GM-CSF的结合。根据这些及之前的实验，我们得出结论，正常人IgG池中含有不同量的针对某些细胞因子的特异性高亲和力Ab，且针对GM-CSF的Ab在这些制剂中构成主要的抗细胞因子活性。这些Ab在IgG治疗后可在体内发生反应。
