title: High levels of anti-cytoskeleton autoantibodies are frequently associated with chronic GVHD.
abstract: Twenty-two patients (acute myeloid leukaemia 13, acute lymphoid leukaemia 5, chronic myeloid leukaemia 4) with an average age of 25 years (range 8-36 years), had received allogeneic bone marrow transplantation (BMT) from an HLA identical sibling. The BMT recipients were followed up for a period of 4-65 months. All patients were given cyclophosphamide, total body irradiation and methotrexate in order to prevent graft-versus-host disease (GvHD). Eleven of 22 patients exhibited chronic graft versus host disease (cGvHD) (extensive in five, limited in six at the time of the study) assessed by clinical and histological parameters. Serum samples were collected from these patients, before BMT (except in one case) and then every 2 or 3 months. Sequential studies to determine the presence of autoantibodies against cytoskeletal proteins (actin, tubulin, myosin), dsDNA and dDNA in these sera were performed by an ELISA method. Simultaneously, immunoelectrophoresis and measurement of complement fractions C3, C4 were performed on each sample. High levels of autoantibodies against cytoskeletal proteins were found in 10/11 patients with cGvHD and were absent in 11/11 patients without cGvHD; none of them exhibited anti-DNA activity. At the same time, C4 levels were decreased in seven of these patients with cGvHD. Monoclonal immunoglobulins IgG and IgM (2-15 g/l) were found in 8/11, but the antibody activity was never found to be located within the M component. These results show a direct relationship between the presence of these autoantibodies and occurrence of cGvHD and indicate that they may constitute an immunological marker related to this complication. However, their predictive value is not clearly evident in this retrospective series as in some patients they preceded clinical signs of cGvHD, whereas in others they were associated with the onset of cGvHD.
authors.affiliation: Institut Pasteur, Unité d'Immunohématologie et d'Immunopathologie, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Dighiero
authors.forename: L
authors.initials: L
authors.lastname: Intrator
authors.forename: C
authors.initials: C
authors.lastname: Cordonnier
authors.forename: P
authors.initials: P
authors.lastname: Tortevoye
authors.forename: J P
authors.initials: JP
authors.lastname: Vernant
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis*; D016026:Bone Marrow Transplantation; D002648:Child; D002908:Chronic Disease; D003598:Cytoskeletal Proteins / Q000276:immunology*; D004247:DNA / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D008297:Male; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D003598:Cytoskeletal Proteins; D004247:DNA