Presenter: K. de Meirlier
(Marc Frémont, Kristin Metzger & Chris Roelant, Vrije Univesititeit, Brussels, Belgium):
Background: Chronic activation of the immune system is present in progressive HIV infection and is a better predictor of disease outcome than plasma viral load.
Several studies suggest that XMRV is involved in the pathophysiology of CFS/ME. The hypothesis was that the systemic immune activation in XMRV positive CFS patient is similar to the one observed in HIV.
Patients and methods: Sixteen CFS patients positive for XMRV were studied with healthy controls. Complete immunophenotyping was performed on venous blood and also elastase activity, C4a, IgG3, cytokines, sCD14, perforin were measured. Stool IgA was also performed independently.
Results: The number of CD3+ and CD57+ lymphocytes was significantly lower compared to the reference values. C4a and elastase activity were significantly higher in the XMRV positive CFS population.
Soluble CD14 (which codes for LPS in plasma) was significantly higher as compared to the reference population. The cytokine panel showed increased IL-10, MCP-1, MIP-1 beta an IL-8 serum levels. Other lymphocyte subsets showed no difference from the reference in the XMRV positive patients. Stool IgA and IgG3 were statistically lower in the XMRV positive patients.
Conclusion: The results of this study show that XMRV positive patients have lymphocyte numbers and CD57+ lymphocytes below normal as is observed in HIV.
XMRV positive CFS patients have an activated innate immune system (elastase activity and C4a are increased) which could be related to microbial translocation as their sCD14 is significantly higher than expected; sCD14 strongly correlates with plasma LPS.
Low stool IgA also indicated dysfunctional muscosa-associated lymphomal tissue (MALT) in XMRV positive CFS patients. Furthermore their IgG3 serum levels are lower than in the controls.
Serum levels of the cytokines IL-8, IL-10, MCP-1 and MIP-1 beta are increased in the patients and might constitute a biological signature for the viral infection.
These observations provide evidence for microbial translocation being part of the pathophysiology of XMRV positive CFS patients.