Hartman K R, Wright D G
Department of Hematology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Blood. 1991 Aug 15;78(4):1096-104.
Anti-neutrophil antibodies have been described in a variety of clinical conditions associated with neutropenia. However, relatively little is known about the antigenic specificities of naturally occurring anti-neutrophil autoantibodies. We investigated the possibility that anti-neutrophil antibodies specific for the neutrophil adhesion glycoprotein (GP) complex CD11b/CD18 might be present in the sera of some patients with autoimmune neutropenia. These membrane GPs have been shown to be highly immunogenic in the production of murine monoclonal antibodies against neutrophil antigens. Moreover, autoantibodies to the platelet membrane GP complex IIb/IIIa, another member of the integrin family of cell adhesion proteins, have been demonstrated in immune thrombocytopenic purpura. Sera from 50 patients known to have anti-neutrophil IgG antibodies were evaluated using an immunobead "antigen capture" assay, modeled after a method used to identify anti-platelet GPIIb/IIIa autoantibodies. This assay detected anti-CD11b/CD18 autoantibodies in seven of the 50 sera. Each of these seven sera demonstrated decreased IgG binding to the neutrophils of a patient with congenital deficiency of CD11b/CD18. The patient with the highest levels of anti-CD11b/CD18 suffered recurrent skin infections and cellulitis, and died of respiratory failure during one of multiple episodes of pneumonia. Purified IgGs from five of these patients demonstrated effects on adhesion and/or opsonin receptor-mediated functions when tested with intact neutrophils in vitro. Our findings indicate that some patients with autoimmune neutropenia have autoantibodies specific for the functionally important neutrophil adhesion proteins CD11b/CD18. Our findings also raise the possibility that these autoantibodies may, in some cases, interfere with neutrophil function, thereby amplifying the risk of infection associated with neutropenia.
抗中性粒细胞抗体已在多种与中性粒细胞减少相关的临床病症中被描述。然而，对于天然存在的抗中性粒细胞自身抗体的抗原特异性，人们了解得相对较少。我们研究了在一些自身免疫性中性粒细胞减少症患者的血清中，可能存在针对中性粒细胞黏附糖蛋白（GP）复合物CD11b/CD18的抗中性粒细胞抗体的可能性。这些膜GP在针对中性粒细胞抗原产生鼠单克隆抗体的过程中已显示出高度免疫原性。此外，在免疫性血小板减少性紫癜中已证实存在针对血小板膜GP复合物IIb/IIIa（细胞黏附蛋白整合素家族的另一个成员）的自身抗体。采用一种仿照用于鉴定抗血小板GPIIb/IIIa自身抗体的方法建立的免疫珠“抗原捕获”试验，对50名已知有抗中性粒细胞IgG抗体的患者的血清进行了评估。该试验在50份血清中的7份中检测到了抗CD11b/CD18自身抗体。这7份血清中的每一份都显示出与一名先天性CD11b/CD18缺陷患者的中性粒细胞的IgG结合减少。抗CD11b/CD18水平最高的患者反复出现皮肤感染和蜂窝织炎，并在多次肺炎发作中的一次因呼吸衰竭死亡。当用完整的中性粒细胞在体外进行测试时，来自其中5名患者的纯化IgG显示出对黏附及/或调理素受体介导功能的影响。我们的研究结果表明，一些自身免疫性中性粒细胞减少症患者具有针对功能重要的中性粒细胞黏附蛋白CD11b/CD18的自身抗体。我们的研究结果还提出了一种可能性，即在某些情况下，这些自身抗体可能会干扰中性粒细胞功能，从而增加与中性粒细胞减少相关的感染风险。
