title: Erythroblastaemia in natalizumab-treated patients with multiple sclerosis.
abstract: BACKGROUND
  Natalizumab is a monoclonal antibody that significantly reduces the occurrence of relapses in relapse-remitting multiple sclerosis (RRMS) patients. Early papers on the clinical use of natalizumab in RRMS patients reported erythroblastemia as occasional and transient.
  
  
  OBJECTIVE
  to determine the prevalence and absolute count of erythroblasts (nucleated red blood cells, NRBCs) in peripheral blood of RRMS patients in different treatment groups and healthy controls from the same geographic area using the same equipment for laboratory analysis.
  
  
  METHODS
  We retrospectively evaluated the samples of 203 consecutive RRMS patients including 26 subjects on natalizumab, 17 on fingolimod, 72 on interferon, 41 on glatiramer acetate, 47 treatment-naïve and 240 healthy controls from the same geographic area. Blood samples were processed using an XN-9000-Hematology Analyzer and subsequent microscopic verification. In the natalizumab-treated patients we performed an additional analysis in order to detect the expression of CD34+ cells in peripheral blood, as confirmation of a bone marrow mobilization.
  
  
  RESULTS
  The prevalence of patients with NRBCs positivity was significantly higher in natalizumab-treated patients (92%) compared with the other treatment groups and healthy controls (0%) (p<0.0005). The median absolute NRBCs count was significantly higher in natalizumab-treated patients (median 0.020, p<0.0005) than in the other treatment groups and healthy controls. Natalizumab-treated patients also had higher levels of white blood cells than all other groups and lower haemoglobin levels than healthy subjects (p<0.01), but no morphologic alterations were evident at a subsequent review of red blood cells, platelets and white blood cells. CD34+ cells levels were consistent with mobilization of haematopoietic stem cells from the bone marrow (median 8 cells/µL, IQR 5-12).
  
  
  CONCLUSIONS
  We confirm erythroblastaemia as a frequent finding of natalizumab treatment in RRMS patients. More extended knowledge and adequate long-term observation of this phenomenon are essential to better understand any pathological implication.
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: saralagioia@yahoo.it.
authors.forename: Sara
authors.initials: S
authors.lastname: La Gioia
authors.affiliation: Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: mikymik89@gmail.com.
authors.forename: Michela
authors.initials: M
authors.lastname: Seghezzi
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: valeria.barcella@gmail.com.
authors.forename: Valeria
authors.initials: V
authors.lastname: Barcella
authors.affiliation: Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: pdominoni@hpg23.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Dominoni
authors.affiliation: Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: tommalloredus@hotmail.it.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mecca
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: barbarafrigeni@hotmail.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frigeni
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: martazaffira@virgilio.it.
authors.forename: Marta Zaffira
authors.initials: MZ
authors.lastname: Conti
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: marcellavedovello@gmail.com.
authors.forename: Marcella
authors.initials: M
authors.lastname: Vedovello
authors.affiliation: Immunohematology and Transfusion Medicine Service, Hospital SS. Trinità, Borgomanero, Italy. Electronic address: matteo.vidali@med.uniupo.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Vidali
authors.affiliation: Neurology and Autoimmune Diseases Unit, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: mrottoli@hpg23.it.
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Rottoli
authors.affiliation: Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address: sbuoro@hpg23.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Buoro
mesh_terms: D000328:Adult; D004900:Erythroblasts; D004906:Erythrocyte Count; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007372:Interferons / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood* / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D000069442:Natalizumab / Q000627:therapeutic use*; D015995:Prevalence; D012189:Retrospective Studies
chemical_list: D007155:Immunologic Factors; D000069442:Natalizumab; D000068717:Glatiramer Acetate; D007372:Interferons; D000068876:Fingolimod Hydrochloride
keywords: Erythroblasts; Multiple sclerosis; Natalizumab