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Is the mechanism of systemic immune activation in XMRV-positive CFS patients similar to that observed in HIV? – Source: 1st International XMRV Workshop Abstract Book, Sep 2010

  [ 15 votes ]   [ Discuss This Article ]
By Kenny De Meirleir, MD, PhD, et al. • • September 22, 2010

Introduction: HIV-1 infection results in chronic activation of the immune system. It was suggested (Brenchley et al., Nature 2006) to occur through a breakdown of the mucosal barrier and stimulation of immune cells by microbial products.

CD14+ monocytes/macrophages secrete soluble CD14 (sCD14), which binds LPS and pro-inflammatory cytokines. In the study cited above it was shown that LPS directly stimulates sCD14 production in vivo.

Earlier our group reported that serum LPS is significantly higher in Chronic Fatigue Syndrome (CFS) patients compared to contact and non-contact controls.

Our hypothesis is that XMRV positive CFS patients also present with immune activation related to mucosal translocation in the gut.

Material & Methods: Fifteen XMRV positive CFS patients who fulfilled the Fukuda et al. criteria (1994) and matched controls were studied. The detection of XMRV was performed by LNCaP co-culture with PMCs as described by Lombardi et al. (2009).

We used commercially available ELISA’s to quantify levels of sCD14, C4a and cytokines. Stool IgA was determined by Diagnos-Techs, Inc (Tukwila, Washington, USA). Statistical analysis was performed using an ANOVA T-test.

Results: XMRV positive CFS patients showed statistically significantly (p<0.05) higher serum levels of sCD14, C4a, IL-8 and MIP1-beta. Stool IgA levels were extremely low (p<0.01) compared to those of healthy controls.*

Conclusion: Although it is too early to conclude that XMRV is a cause of CFS, the similarity with HIV-1 where microbial translocation is a cause of systemic immune activation is striking.

A study in rhesus macaques infected with XMRV showed infected CD4+ T cells in the gastrointestinal tract. The frequency of infected XMRV cells in the gastrointestinal tract in these macaques increased from acute to chronic infection (Sharma et al.). The data of our study along with the findings in XMRV infected macaques ask for [suggests?] confirmation by performing gastrointestinal biopsy studies in XMRV-positive CFS patients.

[* Note: to read the full text of the brief associated article including the statistical analysis table, click HERE.]

Source: 1st International XMRV Workshop Abstract Book, Abstract P_20, pg. 36; Reviews in Antiviral Therapy & Infectious Diseases,  Sep 2010; vol 8. By De Meirleir K, Metzger K, Fremont M, Roelant G. Vrije Universiteit Brussel, Medical physiology, Brussel; RED Laboratories, Science Department, Zellik; Protea Biopharma, Science Department, Brussel, Belgium.

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