Bux Juergen
Institute for Clinical Immunology and Transfusion Medicine, University of Giessen, Germany.
Int J Hematol. 2002 Aug;76 Suppl 1:399-403. doi: 10.1007/BF03165292.
Granulocyte (neutrophil) antibodies can cause autoimmune neutropenia, drug-induced neutropenia, immune neutropenia after bone marrow transplantation, neonatal immune neutropenia, refractoriness to granulocyte transfusions as well as febrile and pulmonary transfusion reactions. In the last decade, considerable progress has been made in the characterization of the implicated antigens. In 1998, the Granulocyte Antigen Working Party of the ISBT introduced a new nomenclature for human neutrophil alloantigens (HNA), which is based on the antigens' glycoprotein location. In the HNA nomenclature the immunogenic (glyco-) proteins are indicated by arabic numbers followed by a letter of the alphabet which identify the (glyco-) proteins' polymorphisms, i.e. the specific antigens. Currently, seven HNA antigens are assigned to five systems. The HNA-1a, HNA-lb and HNA-1c antigens, the former NA1, NA2, and SH antigens, have been identified as polymorphic forms of the neutrophil Fc gamma receptor IIIb (CD16b) encoded by three alleles. Recently, we could elucidate the primary structure of the HNA-2a antigen, the former NB1. We could identify the HNA-2a-bearing glycoprotein as a novel member of the Ly-6/uPAR superfamily which has been clustered meanwhile as CD177. The HNA-3a antigen, the former 5b, is located on a 70-95 kDa glycoprotein. However, its molecular basis is still unknown. Finally, the HNA-4a and HNA-5a antigens, the former MART and OND, were found to be caused by single nucleotide mutations in the alphaM (CD11b) and alphaL (CD11a) subunits of the leucocyte adhesion molecules (beta2 integrins). The glycoproteins CD11b, CD16b, and CD177 have been found to be also frequent targets of autoantibodies - approximately 30% of neutrophil autoantibodies are directed against CD16b. Characterization of granulocyte antigens have expanded our diagnostic tools by the introduction of genotyping techniques and immunoassays for antibody identification. In addition, it allowed new insights in the pathophysiology of immune neutropenias and transfusion reactions. Ongoing studies will further improve the prevention and management of granulocyte antibody-mediated diseases.
粒细胞（中性粒细胞）抗体可导致自身免疫性中性粒细胞减少症、药物性中性粒细胞减少症、骨髓移植后的免疫性中性粒细胞减少症、新生儿免疫性中性粒细胞减少症、粒细胞输注无效以及发热性和肺部输血反应。在过去十年中，在相关抗原的特征描述方面取得了相当大的进展。1998年，国际输血协会粒细胞抗原工作小组引入了一种新的人类中性粒细胞同种异体抗原（HNA）命名法，该命名法基于抗原的糖蛋白定位。在HNA命名法中，免疫原性（糖）蛋白由阿拉伯数字后跟一个字母表示，这些字母标识（糖）蛋白的多态性，即特定抗原。目前，七种HNA抗原被归为五个系统。HNA-1a、HNA-1b和HNA-1c抗原，即以前的NA1、NA2和SH抗原，已被确定为由三个等位基因编码的中性粒细胞Fcγ受体IIIb（CD16b）的多态形式。最近，我们阐明了HNA-2a抗原（以前的NB1）的一级结构。我们可以将携带HNA-2a的糖蛋白鉴定为Ly-6/uPAR超家族的一个新成员，该超家族目前已被归类为CD177。HNA-3a抗原，即以前的5b，位于一种70-95 kDa的糖蛋白上。然而，其分子基础仍然未知。最后，发现HNA-4a和HNA-5a抗原，即以前的MART和OND，是由白细胞粘附分子（β2整合素）的αM（CD11b）和αL（CD11a）亚基中的单核苷酸突变引起的。已发现糖蛋白CD11b、CD16b和CD177也是自身抗体的常见靶点——约30%的中性粒细胞自身抗体针对CD16b。粒细胞抗原的特征描述通过引入基因分型技术和用于抗体鉴定的免疫测定法扩展了我们的诊断工具。此外，它使我们对免疫性中性粒细胞减少症和输血反应的病理生理学有了新的认识。正在进行的研究将进一步改善粒细胞抗体介导疾病的预防和管理。
