Sequence analysis of monoclonal antibodies derived from a patient with idiopathic thrombocytopenic purpura.
Autoantibodies directed at the platelet membrane glycoprotein Ib (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.
Hiraiwa
A
A
Virginia Mason Research Center, Seattle, WA 98101.
Nugent
D J
DJ
Milner
E C
EC
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D001792:Blood Platelets / Q000276:immunology; D002460:Cell Line; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D039421:Integrin alpha2; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D011696:Purpura, Thrombocytopenic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C056564:ITGA2B protein, human; D007135:Immunoglobulin Variable Region; D039421:Integrin alpha2; D008562:Membrane Glycoproteins; C040580:glycoprotein GP III