Stahl D, Sibrowski W
Institute for Transfusion Medicine, University of Münster, Domagkstrasse 11, D-48149 Münster, Germany.
J Autoimmun. 2005 Dec;25(4):272-82. doi: 10.1016/j.jaut.2005.08.003. Epub 2005 Oct 20.
Warm autoimmune hemolytic anemia (WAIHA) is characterized by polyclonal IgG autoantibodies binding to red blood cells (RBC). The characterization of the autoantigen in WAIHA has not yet led to definitive results, and the etiology of RBC autoantibodies remains unclear. An altered control of self-reactive IgG by autologous IgM has been proposed as the underlying mechanism of disease in WAIHA, suggesting that IgM-IgG immune complexes contribute to the pathophysiology of the disease. In the present study, we purified and characterized IgM from plasma of WAIHA patients and from healthy controls using FPLC-based protocols and optical biosensor technology, and investigated IgG present within the IgM fractions. We provide evidence that IgM-IgG immune complexes in plasma and associated with the RBC membrane are the characteristic feature of WAIHA, independent of the etiology of the disease. IgM-IgG immune complexes of WAIHA patients differ from IgM-IgG immune complexes of healthy individuals with regard to quantity and to structural composition. The data suggest that self-immunoglobulin is the original autoantigen underlying WAIHA. The molecular characterization of IgM-IgG immune complexes may define new targets for therapeutic intervention in WAIHA.
温抗体型自身免疫性溶血性贫血（WAIHA）的特征是多克隆IgG自身抗体与红细胞（RBC）结合。WAIHA中自身抗原的特征尚未得出明确结果，RBC自身抗体的病因仍不清楚。有人提出，自体IgM对自身反应性IgG的控制改变是WAIHA疾病的潜在机制，这表明IgM-IgG免疫复合物参与了该疾病的病理生理过程。在本研究中，我们使用基于快速蛋白液相色谱（FPLC）的方法和光学生物传感器技术，从WAIHA患者和健康对照者的血浆中纯化并鉴定了IgM，并研究了IgM组分中的IgG。我们提供的证据表明，血浆中以及与RBC膜相关的IgM-IgG免疫复合物是WAIHA的特征性特征，与疾病的病因无关。WAIHA患者的IgM-IgG免疫复合物在数量和结构组成方面与健康个体的IgM-IgG免疫复合物不同。数据表明，自身免疫球蛋白是WAIHA潜在的原始自身抗原。IgM-IgG免疫复合物的分子特征可能为WAIHA的治疗干预确定新的靶点。
