Bruin M C, von dem Borne A E, Tamminga R Y, Kleijer M, Buddelmeijer L, de Haas M
Department of Hematology of the University Hospital for Children and Youth 'The Wilhelmina Childrens Hospital,' Utrecht, The Netherlands.
Blood. 1999 Sep 1;94(5):1797-802.
Autoimmune neutropenia (AIN) in children can be divided into 2 forms. In primary AIN, neutropenia is the sole abnormality, and although neutrophil counts are generally below 500 microL(-1), mild bacterial infections occur. Primary AIN is mostly seen in young children and shows a self-limited course. AIN occurring in association with autoimmune diseases (secondary AIN) often shows more severe infectious complications. We analyzed clinical and serological data from 28 pediatric patients with AIN to evaluate whether there is a possible relationship between specificity of the neutrophil autoantibodies and the clinical course of the disease. Specificity of the circulating antibodies was determined with the indirect granulocyte immunofluorescence test (GIFT) and a panel of phenotyped donor neutrophils. The samples were further analyzed in the monoclonal antibody immobilization of granulocyte antigens assay (MAIGA) for neutrophil antigen (NA)1, NA2, CD11a, and CD11b specificity. With the indirect GIFT, an antibody specificity was deduced in 26 of the 28 analyzed samples. In all but 3 sera from patients with primary AIN, NA1-(76%) or NA2-(10%) specific antibodies were detected with the indirect GIFT. In 2 samples, the reactivity in the indirect GIFT was too weak to draw conclusions, but the MAIGA showed NA1 and/or NA2 specificity of the antibodies. One serum, from a patient with primary AIN with a persistent neutropenia for more than 6 years, contained NA1, possibly pan-FcgammaRIIIb, and CD11a antibodies. In 4 sera from patients with primary AIN, weak antibodies with CD11a or CD11b specificity were detected with the MAIGA. Sera from 7 patients with secondary AIN contained in all cases antibodies with pan-FcgammaRIIIb specificity, as deduced from the indirect GIFT results and absorbance/elution experiments performed with 2 sera. The MAIGA confirmed this for only 1 of the 5 tested sera. Furthermore, CD11a antibodies were detected in 1 of the 5 tested sera. In conclusion, our results indicate that primary AIN is usually associated with NA-specific antibodies, whereas secondary AIN seems to be associated with pan-FcgammaRIIIb antibodies. Thus, characterization of the antibodies in sera from children with AIN discriminates patients with primary AIN from those with secondary AIN.
儿童自身免疫性中性粒细胞减少症（AIN）可分为两种形式。在原发性AIN中，中性粒细胞减少是唯一的异常情况，尽管中性粒细胞计数通常低于500/μL，但仍会发生轻度细菌感染。原发性AIN多见于幼儿，病程呈自限性。与自身免疫性疾病相关的AIN（继发性AIN）往往会出现更严重的感染并发症。我们分析了28例儿科AIN患者的临床和血清学数据，以评估中性粒细胞自身抗体的特异性与疾病临床病程之间是否存在可能的关联。通过间接粒细胞免疫荧光试验（GIFT）和一组表型分型的供体中性粒细胞来确定循环抗体的特异性。样本进一步通过粒细胞抗原单克隆抗体固定试验（MAIGA）分析中性粒细胞抗原（NA）1、NA2、CD11a和CD11b的特异性。通过间接GIFT，在28份分析样本中的26份中推断出抗体特异性。除了3份原发性AIN患者的血清外，在其余所有血清中，通过间接GIFT检测到NA1特异性抗体（76%）或NA2特异性抗体（10%）。在2份样本中，间接GIFT中的反应性过弱无法得出结论，但MAIGA显示抗体具有NA1和/或NA2特异性。1份来自一名原发性AIN且持续性中性粒细胞减少超过6年患者的血清，含有NA1、可能的全FcγRIIIb和CD11a抗体。在4份原发性AIN患者的血清中，通过MAIGA检测到具有CD11a或CD11b特异性的弱阳性抗体。根据间接GIFT结果以及对2份血清进行的吸光度/洗脱实验推断，7例继发性AIN患者的血清在所有情况下均含有具有全FcγRIIIb特异性的抗体。MAIGA仅在5份检测血清中的1份中证实了这一点。此外，在5份检测血清中的1份中检测到了CD11a抗体。总之，我们的结果表明，原发性AIN通常与NA特异性抗体相关，而继发性AIN似乎与全FcγRIIIb抗体相关。因此，对AIN患儿血清中的抗体进行特征分析可区分原发性AIN患者和继发性AIN患者。
