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. 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.
Subject(s)
Herpesviridae Infections/complications , Herpesviridae Infections/epidemiology , Histiocytosis, Langerhans-Cell/complications , Histiocytosis, Langerhans-Cell/epidemiology , Adolescent , Adult , Antigens, CD1/biosynthesis , Antigens, CD20/biosynthesis , CD79 Antigens/biosynthesis , Case-Control Studies , Child , Child, Preschool , Cohort Studies , Cytomegalovirus/metabolism , Herpesviridae Infections/diagnosis , Herpesvirus 4, Human/metabolism , Herpesvirus 6, Human/metabolism , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/virology , Humans , Immunosuppressive Agents/pharmacology , InfantABSTRACT
The aim of this study was to evaluate the T-cell receptor (TCR) Vbeta repertoire in the two main histological subtypes of nodal non-anaplastic peripheral T-cell lymphoma: Not Otherwise Specified (NOS) and angioimmunoblastic lymphoma (AIL). Frozen lymph node tissues of eight NOS and six AIL were analyzed. A reverse transcriptase polymerase chain reaction (RT-PCR) was carried out to assess the expression of the 24 Vbeta gene families. Our study showed a broad TCR Vbeta repertoire in AIL and NOS, with a slight increase in the number of Vbeta families in AIL (16 vs 10 on agarose gels). Nevertheless, there was a clear difference in four cases. A predominant Vbeta family was observed in two NOS, whereas no predominant Vbeta family was observed in the AIL. Two AIL showed the whole Vbeta repertoire, whereas it was never observed in NOS. This pattern may help to categorize these histopathological entities and further suggests a differential T-cell response. These results show that numerous reactive T-cells are present both in AIL and NOS. Possibly, they play a role in the growth of these lymphomas.
