Abstract 1671: Human Cytomegalovirus- A Possible Activator of the Immune System in Polymyositis and Dermatomyositis
Authors
Andreas E. R. Fasth1, Afsar Rahbar2, Maryam Dastmalchi1, Cecilia Söderberg-Naucler2, Christina Trollmo1, Ingrid E. Lundberg1, Vivianne Malmström1.
Background
We have previously shown increased frequencies of hyper responsive and perforin-expressing CD4+CD28null and CD8+CD28null T cells in the circulation of patients with polymyositis (PM) and dermatomyositis (DM). CD28null T cells also constituted the major cell type infiltrating muscle tissue in these patients. Increased frequencies of CD4+CD28null and CD8+CD28null T cells have previously been reported in patients with chronic viral infections. Here we have investigated the association of human cytomegalovirus infection (HCMV) to the frequency of circulating CD28null T cells in patients with DM and PM.
Methods
Serum samples from 65 patients diagnosed with DM (n = 23) or PM (n = 42) were investigated for IgM and IgG reactivity against HCMV by ELISA. The frequencies of CD4+ and CD8+CD28null T cells were analyzed by flow cytometry. HCMV reactivity of CD28null T cells from 5 patients positive for HCMV-IgG and 4 patients negative for HCMV-IgG was tested by in vitro-stimulation with HCMVderived peptides, HCMV-pp65 and HCMV-IEA. Upregulated levels of intracellular IFN-γ was used as readout for activated T cells and analyzed by flow cytometry.
Results
ELISA results indicated that 72% of the DM and PM patients are IgG seropositive for HCMV to the same frequency (72%) as the average population. 17% were HCMV-IgM positive. However, increased CD4+ and CD8+ CD28null T cell populations were mainly found in individuals seropositive for HCMV IgG, indicating
a latent virus infection (figure). Results from the in vitro reactivity assays confirmed the associations to HCMV since the CD28null T cells produced IFN-γ following activation by HCMV-derived peptides. Interestingly, increased CD4+ and CD8+ CD28null T cell populations were seen already at disease onset.
Conclusion
This study demonstrated that the increase of CD4+ and CD8+ CD28null T cells in patients with DM and PM is strongly associated with chronic HCMV infection. Hence we suggest a role for HCMV infection in the pathogenesis in subsets of DM and PM and that the effector T cells are of CD28null phenotype.
Editorial Comment
Viral targets have long been thought to be possibly responsible for initiation of te immune response in DM/PM. This study provides intriguing evidence that CMV may indeed play that role.
