Epitopes described in "Autoantibodies frequently detected in patients with aplastic anemia."

Article Authors:Naoto Hirano; Marcus O Butler; Michael S Von Bergwelt-Baildon; Britta Maecker; Joachim L Schultze; Kevin C O'Connor; Peter H Schur; Seiji Kojima; Eva C Guinan; Lee M Nadler
Article Title:Autoantibodies frequently detected in patients with aplastic anemia.
Reference Detail
Reference ID:1006361
Abstract:Although accumulating evidence strongly suggests that aplastic anemia (AA) is a T cell-mediated autoimmune disease, no target antigens have yet been described for AA. In autoimmune diseases, target autoantigens frequently induce not only cellular T-cell responses but also humoral B-cell responses. We hypothesized that the presence of antigen-specific autoantibodies could be used as a "surrogate marker" for the identification of target T-cell autoantigens in AA patients. We screened a human fetal liver library for serologic reactivity against hematopoietic stem/progenitor cell antigens and isolated 32 genes. In 7 of 18 AA patients, an immunoglobulin G (IgG) antibody response was detected to one of the genes, kinectin, which is expressed in all hematopoietic cell lineages tested including CD34+ cells. No response to kinectin was detected in healthy volunteers, multiply transfused non-AA patients, or patients with other autoimmune diseases. Epitope mapping of IgG autoantibodies against kinectin revealed that the responses to several of the epitopes were shared by different AA patients. Moreover, CD8+ cytotoxic T cells raised against kinectin-derived peptides suppressed the colony formation of granulocyte macrophage colony-forming units (CFU-GMs) in an HLA class I-restricted fashion. These results suggest that kinectin may be a candidate autoantigen that is involved in the pathophysiology of AA.
Affiliations:Dana-Farber Cancer Institute, Department of Medical Oncology, 44 Binney St, Boston MA 02115, USA. naoto_hirano@dfci.harvard.edu
Reference Type:Literature
PubMed ID:12947009
Journal Volume:102
Article Pages:4567-75
Journal ISSN:1528-0020
Article Chemical List:Autoantibodies;Autoantigens;Biological Markers;DNA, Complementary;HLA-A2 Antigen;Immunoglobulin G;KTN1 protein, human;Membrane Proteins;Recombinant Fusion Proteins
Article MeSH List:Anemia, Aplastic(etiology; immunology); Anemia, Sickle Cell(immunology); Antibody Specificity; Autoantibodies(blood); Autoantigens(biosynthesis; blood; genetics; immunology); Autoimmune Diseases(blood; immunology); Biological Markers; Blood Transfusion; Colony-Forming Units Assay; DNA, Complementary(genetics); Gene Expression Regulation; Gene Library; HLA-A2 Antigen(immunology); Hematopoietic Stem Cells(classification; metabolism); Hepatitis, Viral, Human(complications; immunology); Humans; Immunoglobulin G(blood; immunology); Membrane Proteins(biosynthesis; blood; genetics; immunology); Recombinant Fusion Proteins(immunology); T-Lymphocytes(immunology); Thalassemia(immunology)
Curation Last Updated:2014-10-03 20:47:07