HUMAN MONOCLONAL ANTIBODIES

我们的目标是确定自身免疫反应的性质， 特发性血小板减少性紫癜（ITP）患者。 我们特别 将从爱泼斯坦巴尔体内分离出人类单克隆抗血小板抗体 从ITP患者分离的病毒转化的B淋巴细胞， 鉴定血小板自身抗原。 这种方法允许我们检查 产生的自身抗体的谱和这些表位的性质 作为膜靶抗原的GPIIb-IIIa或GPIb。 我们的长期 目的是为ITP的病因学提供新的见解，并开发更安全的 慢性ITP患者的治疗方案。 我们明年的目标包括： 1.） 抗GPIb和抗GPIb-IIIa特异性自身抗体细胞的产生 来自一系列已知含有血清学定义的 血浆中的抗血小板抗体。 2.） 检查这些细胞系的可变基因区， 确定a.）存在的多态性程度和B.）联盟 这些特定的体细胞突变与抗GPIb反应性。 3.）第三章 利用人单克隆抗GPIb-IIIa或Ib-IX抗体 绘制这些分子上的免疫原性区域。 4）继续使用这些抗独特型抗体进行检测， GPIb特异性抗体的鉴定 ITP，并确定那些患者中，更积极的治疗， 可以指示方案。

Our objective is to define the nature of the autoimmune response in patients with idiopathic thrombocytopenic purpura (ITP). Specifically, we will isolate human monoclonal antiplatelet antibodies from Epstein Barr Virus transformed B lymphocytes, isolated from patients with ITP, to identify platelet autoantigens. This approach allows us t examine the spectrum of autoantibodies produced and the nature of those epitopes of GPIIb-IIIa or GPIb which serve as membrane target antigens. Our long term goal is to provide new insights into the etiology of ITP and develop safer treatment regimens for those patients with chronic ITP. Our goals in the next year include: 1.) production of anti-GPIb and anti-GPIb-IIIa specific autoantibody cell lines from a series of patients known to contain serologically defined idiotypic antiplatelet antibodies in their plasma. 2.) examination of the variable gene region of these cell lines to determine the a.)degree of polymorphism present and b.) the association of these specific somatic mutations with anti-GPIb reactivity. 3.) utilization of human monoclonal anti-GPIb-IIIa or Ib-IX antibodies to map immunogenic regions on these molecules. 4,) Continued use of these anti-idiotypic antibodies for the detection and characterization of GPIb-specific antibodies in the sera of patients with ITP and to identify those patients in whom more aggressive therapeutic regimens may be indicated.