Immune Abnormalities in CFS - Two New Studies

Last week we introduced a new piece of the CFS/FMS puzzle that offered several new possibilities for both testing and therapy. It has been stimulating the discussion I had hoped for, and while patients are adding in the Coenzyme Q10 and Pregnenolone to see how much they help, a number of CFS physicians have expressed interest in adding in the statins as a therapeutic trial for CFS/FMS patients with resistant and persistent chronic viral infection. So I suspect we will be getting clinical feedback in the upcoming six months.

Meanwhile, with perfect timing, two excellent new studies have just come out that look at the immune abnormalities in CFS. Their conclusions? There are many cytokine (immune chemical) abnormalities in CFS, and the pattern they make is quite characteristic for CFS. This may allow creation of a lab test panel that, according to researchers from Bond University in Australia (who partnered with Dr. Nancy Klimas, one of my favorite CFS researchers) "may serve as biomarkers in CFS/ME patients with potential for an application as a diagnostic tool."

Another study done by WPI found that in CFS patients whose illness had a sudden flu-like onset, and who had a positive XMRV test in their lab, the cytokine lab panel was like a CFS "fingerprint" and was able to distinguish these patients from a healthy group with excellent accuracy.

Given that the WPI (which introduced the XMRV virus concept) is actively involved with making XMRV testing available to the public, I would not be surprised if they move forward to also make this immune panel lab test available to the public.

So what's new? Several things:

1. Two more studies are showing clear-cut immune abnormalities in CFS. This adds to the ever-growing body of research showing that CFS is very real and physical, and further confirms that those who believe that people with CFS are crazy are, well, maybe just plain nuts themselves!
2. Though relying on a single immune abnormality for testing is not especially helpful, looking at a pattern of immune test abnormalities may be a reliable way to confirm the diagnosis of CFS, and to document CFS for medical and legal purposes. This will take time to gain general acceptance, but these two studies represent a major leap forward.
3. The pattern of immune abnormalities may help define which subset of CFS/FMS patients have a predominantly infectious process vs. other triggers. This will further help tailor therapy.
4. Among the immune abnormalities found, there are alterations in interferon levels (low interferon alpha and elevated interferon beta and gamma). These go along with the new theory I proposed last week.

All in all, research is moving forward well in a number of exciting directions. For the more science minded, the following is an overview of the immune abnormalities seen in these two new studies.

Study 1 — Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

This study looked at multiple immune lab measures in 95 CFS/ME patients and 50 healthy controls. Allparticipants were assessed on natural killer (NK) and CD8+T cellcytotoxic activities, Th1 and Th2 cytokine profile of CD4+T cells,expression of vasoactive intestinal peptide receptor 2 (VPACR2),levels of NK phenotypes (CD56bright and CD56dim) and regulatory Tcells expressing FoxP3 transcription factor.

Compared to healthy individuals, CFS/ME patients displayed significantincreases in IL-10, IFN-gamma, TNF-alpha, CD4+CD25+ T cells, FoxP3 andVPACR2 expression. Cytotoxic activity of NK and CD8+T cells and NKphenotypes, in particular the CD56bright NK cells were significantlydecreased in CFS/ME patients. Additionally granzyme A and granzyme Kexpression were reduced while expression levels of perforin weresignificantly increased in the CFS/ME population relative to thecontrol population.

The authors concluded "These data suggest significant dysregulation ofthe immune system in CFS/ME patients … which may serve asbiomarkers in CFS/ME patients with potential for an application as adiagnostic tool."

Study 2 — Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature

In the second study done at the WPI, multiple immune changes were seen. Most interesting to me, given the role interferon (IFN) may play in CFS discussed in our recent article, were the authors findings that "the subtle but significant decrease in IFN-α, as compared to the levels of healthy controls, may be involved in the persistent viral reactivation seen in CFS patients ... A basal level of IFN below a normal threshold results in the inability of the host to mount the proper innate immune response, including viral clearance ... Certainly, the observed decrease in IFN-α and the refractory production of IFN-γ [gamma] and IFN-β [beta] is consistent with clinical observations in CFS regarding their inability to control viral infections properly. These observations may also provide clues to disease pathology and suggest therapy options."

In my reading of the data, it does not really address whether XMRV is present (as the authors imply), but does clearly suggest that there are widespread immune abnormalities in those with CFS that had an acute "viral or flu-like" onset. To confirm that this pattern is specific to XMRV, they would have needed to compare the findings to CFS patients with an acute viral onset who were XMRV negative. This study shows drops in interferon A, but mild yet clinically significant elevations in interferon Beta and Gamma. These interferon changes may be a major control factor for many cytokine changes. What is truly exciting about this study is that for those whose CFS began with a flu-like illness, "This study identifies a signature of 10 cytokines and chemokines which correctly identifies XMRV/CFS patients with 93% specificity and 96% sensitivity." This means it was only negative in 7% of the CFS cases and only positive in 4% of healthy people — which is better than most medical tests!

References

Study 1 — Immunological abnormalities as potential biomarkers in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Ekua W Brenu, Mieke L van Driel, Don R Staines, Kevin J Ashton,Sandra B Ramos, James Keane, Nancy G Klimas and Sonya MMarshall-Gradisnik. Journal of Translational Medicine. May 28, 2011, 9:81doi:10.1186/1479-5876-9-81

Study 2 — Xenotropic Murine Leukemia Virus-related Virus-associated Chronic Fatigue Syndrome Reveals a Distinct Inflammatory Signature. VC Lombardi, KS Hagen, KW Hunter, JW Diamond, J Smith-Gagen, W Yang, and JA Mikovits. In Vivo. 2011; 25: 307-314