title: Herpes-virus infection in patients with Langerhans cell histiocytosis: a case-controlled sero-epidemiological study, and in situ analysis.
abstract: BACKGROUND
  Langerhans cell histiocytosis (LCH) is a rare disease that affects mainly young children, and which features granulomas containing Langerhans-type dendritic cells. The role of several human herpesviruses (HHV) in the pathogenesis of LCH was suggested by numerous reports but remains debated. Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with LCH based on the detection of these viruses in clinical samples.
  
  
  METHODS
  We have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters of antibody response and the plasma viral load in a cohort of 83 patients and 236 age-matched controls, and the presence and cellular localization of the viruses in LCH tissue samples from 19 patients.
  
  
  RESULTS
  The results show that prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not differ between patients and controls. EBV was found by PCR in tumoral sample from 3/19 patients, however, EBV small RNAs EBERs -when positive-, were detected by in situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC. HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number and viral Ag could not be detected in biopsies. CMV was not detected by PCR in this series.
  
  
  CONCLUSIONS
  Therefore, our findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma. The latter observation can be attributed to the immunosuppressive micro environment found in LCH granuloma.
authors.affiliation: Laboratory of biology of the mononuclear phagocyte system, INSERM U838, University Paris-Descartes, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Jeziorski
authors.forename: Brigitte
authors.initials: B
authors.lastname: Senechal
authors.forename: Thierry Jo
authors.initials: TJ
authors.lastname: Molina
authors.forename: Francis
authors.initials: F
authors.lastname: Devez
authors.forename: Marianne
authors.initials: M
authors.lastname: Leruez-Ville
authors.forename: Patrice
authors.initials: P
authors.lastname: Morand
authors.forename: Christophe
authors.initials: C
authors.lastname: Glorion
authors.forename: Ludovic
authors.initials: L
authors.lastname: Mansuy
authors.forename: Joel
authors.initials: J
authors.lastname: Gaudelus
authors.forename: Marianne
authors.initials: M
authors.lastname: Debre
authors.forename: Francis
authors.initials: F
authors.lastname: Jaubert
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Seigneurin
authors.forename: Caroline
authors.initials: C
authors.lastname: Thomas
authors.forename: Irene
authors.initials: I
authors.lastname: Joab
authors.forename: Jean
authors.initials: J
authors.lastname: Donadieu
authors.forename: Frederic
authors.initials: F
authors.lastname: Geissmann
mesh_terms: D000293:Adolescent; D000328:Adult; D018949:Antigens, CD1 / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis; D051925:CD79 Antigens / Q000096:biosynthesis; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000378:metabolism; D006566:Herpesviridae Infections / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology*; D004854:Herpesvirus 4, Human / Q000378:metabolism; D015654:Herpesvirus 6, Human / Q000378:metabolism; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications* / Q000175:diagnosis / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007223:Infant
chemical_list: D018949:Antigens, CD1; D018951:Antigens, CD20; C419393:CD1a antigen; D051925:CD79 Antigens; D007166:Immunosuppressive Agents