Herpes-virus infection in patients with Langerhans cell histiocytosis: a case-controlled sero-epidemiological study, and in situ analysis.
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.
Jeziorski
Eric
E
Laboratory of biology of the mononuclear phagocyte system, INSERM U838, University Paris-Descartes, Paris, France.
Senechal
Brigitte
B
Molina
Thierry Jo
TJ
Devez
Francis
F
Leruez-Ville
Marianne
M
Morand
Patrice
P
Glorion
Christophe
C
Mansuy
Ludovic
L
Gaudelus
Joel
J
Debre
Marianne
M
Jaubert
Francis
F
Seigneurin
Jean-Marie
JM
Thomas
Caroline
C
Joab
Irene
I
Donadieu
Jean
J
Geissmann
Frederic
F
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
D018949:Antigens, CD1; D018951:Antigens, CD20; C419393:CD1a antigen; D051925:CD79 Antigens; D007166:Immunosuppressive Agents