title: Autoantibodies frequently detected in patients with aplastic anemia.
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.
authors.affiliation: Dana-Farber Cancer Institute, Department of Medical Oncology, 44 Binney St, Boston MA 02115, USA. naoto_hirano@dfci.harvard.edu
authors.forename: Naoto
authors.initials: N
authors.lastname: Hirano
authors.forename: Marcus O
authors.initials: MO
authors.lastname: Butler
authors.forename: Michael S
authors.initials: MS
authors.lastname: Von Bergwelt-Baildon
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Kevin C
authors.initials: KC
authors.lastname: O'Connor
authors.forename: Peter H
authors.initials: PH
authors.lastname: Schur
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Eva C
authors.initials: EC
authors.lastname: Guinan
authors.forename: Lee M
authors.initials: LM
authors.lastname: Nadler
mesh_terms: D000741:Anemia, Aplastic / Q000209:etiology / Q000276:immunology*; D000755:Anemia, Sickle Cell / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D015415:Biomarkers; D001803:Blood Transfusion; D003114:Colony-Forming Units Assay; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D015723:Gene Library; D015789:HLA-A2 Antigen / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000378:metabolism; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013789:Thalassemia / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D018076:DNA, Complementary; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; C088547:KTN1 protein, human; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins