Herpes-virus infection in patients with Langerhans cell histiocytosis: a case-controlled sero-epidemiological study, and in situ analysis

PLoS One. 2008 Sep 23;3(9):e3262. doi: 10.1371/journal.pone.0003262.


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.

Methodology: 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.

Principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antigens, CD1 / biosynthesis
  • Antigens, CD20 / biosynthesis
  • CD79 Antigens / biosynthesis
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cytomegalovirus / metabolism
  • Herpesviridae Infections / complications*
  • Herpesviridae Infections / diagnosis
  • Herpesviridae Infections / epidemiology*
  • Herpesvirus 4, Human / metabolism
  • Herpesvirus 6, Human / metabolism
  • Histiocytosis, Langerhans-Cell / complications*
  • Histiocytosis, Langerhans-Cell / diagnosis
  • Histiocytosis, Langerhans-Cell / epidemiology*
  • Histiocytosis, Langerhans-Cell / virology
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Infant


  • Antigens, CD1
  • Antigens, CD20
  • CD1a antigen
  • CD79 Antigens
  • Immunosuppressive Agents