Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis...

halcyon

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I'm guessing this is a new paper by Maes. No author is listed but it sounds like him and he likes to publish in this journal.

Neuro Endocrinol Lett. 2015 Nov 28;36(5):439-446. [Epub ahead of print]
Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune.
[No authors listed]
Abstract
BACKGROUND:
There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS.

METHODS:
Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40).

RESULTS:
The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin.

CONCLUSIONS:
The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.
 

halcyon

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The CD38 finding stands out to me. Among other things, CD38 is a marker of immune activation on T lymphocytes, notably in chronic infection such as HIV. In untreated HIV an increase in CD8+CD38+ T lymphocytes is seen and upon antiviral treatment this cell population is found to diminish.
 

halcyon

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I found this study where they found no significant differences in percentages of CD8+CD8+ in CFS patients, but oh wait...
Surface and intracellular immunologic and apoptotic markers and functional lymphocyte assays after stimulation with anti-CD3/anti-CD28 antibodies or phytohemagglutinin (PHA) were studied in 44 patients fulfilling the Oxford criteria for chronic fatigue syndrome (CFS).
:grumpy:
 

Richard7

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Interesting, I don't really understand all of the immune stuff. I do have some pathology that shows that I was high outside the normal range for cd3 and cd8, and low outside the normal range for cd4 a year ago. So that part at least matches the pattern. But my cd19 and hla-dr were normal range and I have no data on cd38.

It seems strange that the abstract states that these patterns are significant, but does not state the p value or the effect size.

Is there some sense in which this pattern is different to a normal person fighting of a virus?
 

halcyon

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Is there some sense in which this pattern is different to a normal person fighting of a virus?
Good question and I wish I knew. As I mentioned, elevated CD8+CD38+ is seen in HIV infection. Potentially it's not seen in HCV infection though I found conflicting results there. It's seen in transplant patients with active CMV. That's what I've come across so far.
 

halcyon

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There's a 2005 study by Komaroff using Fukuda that found the same CD38+ elevation. Then there's another Oxford criteria study from 1996 that (surprise surprise) didn't find it.
 
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nandixon

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There's a 2005 study by Komoroff using Fukuda that found the same CD38+ elevation. Then there's another Oxford criteria study from 1996 that (surprise surprise) didn't find it.
Very iteresting. The 2005 work used the 1988 CDC criteria for CFS, and while the increased CD38 didn't reach statistical significance:

Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression [2005]

Patients with CFS tended to have increased numbers of activated cytotoxic T cells, as assessed by co-expression of CD8 with CD38 and HLA-DR (Table 2). Numbers of activated CD8+/CD38+ cells tended to be increased in patients with CFS compared to patients with MS, and numbers of CD8+/HLA-DR+cells tended to be higher in patients with CFS than in healthy controls. However, these differences did not achieve statistical significance.

it makes one wonder if they had used the same criteria as in the 2015 study of the original post if it would have, especially since "highly significant" correlations were found in the later study.

What criteria was used for the 2015 study? I'm wondering if we might have lost 10 years of having a marker (i.e., increased CD38+ T-cells) for a particular ME/CFS subset due to too loose criteria being used in the 2005 study.