Sequence Analysis of Monoclonal Antibodies Derived from a Patient with Idiopathic Thrombocytopenic Purpura
作者:
HiraiwaAkikazu,
NugentDiane J.,
MilnerEric C. B.,
期刊:
Autoimmunity
(Taylor Available online 1990)
卷期:
Volume 8,
issue 2
页码: 107-113
ISSN:0891-6934
年代: 1990
DOI:10.3109/08916939008995728
出版商: Taylor&Francis
关键词: Anti-platelet autoantibodies;immunoglobulin heavy chain variable region genes;idiopathic thrombocytopenic purpura;platelet glycoprotein lb
数据来源: Taylor
摘要:
Autoantibodies directed at the platelet membrane glycoprotein lb (GPIb) can mediate a severe form of idiopathic thrombocytopenic purpura (ITP). The platelet-specific antibody from plasma of one patient (DM) with this form of ITP displays a public idiotype termed DMId. The DMId idiotype has been found in the plasma of several patients with ITP, usually in association with GPIb-specific autoantibodies. As a step in the understanding of the molecular genetics of this form of ITP we have determined the nucleotide sequences of expressed V region genes selected from a panel of five human lymphoblastoid cell lines derived from patient DM. Two of the lines secreted antibodies that bound GPIb, and three of the lines secreted antibodies that expressed DMId. The H chain sequences of the DMId-positive antibodies and of one of the GPIb-binding antibodies belong to the VH4 family. The second GPIb-binding antibody belongs to the VH1 family. All have multiple substitutions from previously published sequences giving these antibodies the appearance of having been antigen driven. These results are consistent with the hypothesis that autoantibodies in ITP arise from a“normal”immune response inappropriately directed at platelet antigens. Further, our results suggest that VH4 gene segments may be recruited preferentially into the DMId-positive, GPIb-specific autoantibody response.
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