title: Detection of erythroblast antibodies in mitogen-stimulated bone marrow cultures from patients with myelodysplastic syndromes.
abstract: Low-risk myelodysplastic syndromes (MDS) show several immunologic abnormalities, including increased frequency of autoimmune manifestations and/or overt autoimmune diseases, whose prognostic significance still remains controversial.
  
  
  
  We studied the presence of erythroblast antibodies in mitogen-stimulated bone marrow (BM) cultures of 70 patients with early-stage MDS (refractory anemia and refractory anemia with ringed sideroblasts).
  
  
  
  Sixty-six percent of patients showed positive erythroblast antibodies, along with BM erythroid hyperplasia and a hemolytic picture in the peripheral blood. Supernatants from positive cultures induced an increase of overall cellularity, the appearance of erythroblastic clustering, and dyserythropoietic signs in normal BM. We identified CD45(dim) Gly-A(dim) CD71(bright) cells (red blood cell precursors at different maturation stage) as the target of the antibodies. Erythropoietin (EPO) levels were reduced and EPO receptors (EPO-R) increased in BM culture supernatants from positive patients. However, flow cytometric analysis showed that neither EPO nor EPO-R was involved in an abnormal stimulation driven by these autoantibodies. Values of the proapoptotic protein Bax were increased in positive patients and Bcl-2 levels were decreased, although not significantly.
  
  
  
  MDS patients with anti-erythroblast autoimmunity showed increased BM apoptosis, suggesting that the autoimmune reaction may contribute to an unfavorable BM microenvironment for optimal erythropoiesis.
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Anna
authors.initials: A
authors.lastname: Zaninoni
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Francesca G
authors.initials: FG
authors.lastname: Imperiali
authors.affiliation: Servizio di Citofluorimetria, U.O. Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologiche Dipartimento dei Servizi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Giulia
authors.initials: G
authors.lastname: Soverini
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Francesca
authors.initials: F
authors.lastname: Binda
authors.affiliation: Servizio di Citofluorimetria, U.O. Laboratorio Centrale di Analisi Chimico Cliniche e Microbiologiche Dipartimento dei Servizi, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Laura
authors.initials: L
authors.lastname: Porretti
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.|Università Degli Studi di Milano, Milano, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
authors.affiliation: U.O. Oncoematologia and, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano.
authors.forename: Wilma
authors.initials: W
authors.lastname: Barcellini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology*; D004900:Erythroblasts / Q000187:drug effects* / Q000276:immunology*; D004921:Erythropoietin / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D009190:Myelodysplastic Syndromes / Q000276:immunology*
chemical_list: D000906:Antibodies; C554270:EPO protein, human; D007074:Immunoglobulin G; D008934:Mitogens; D004921:Erythropoietin