Diverse studies suggereren een mogelijk verband tussen ME/CVS en kanker,

mogelijk als gevolg van specifieke immunologische afwijkingen,

zoals de slechte werkzaamheid van NK-cellen (verminderde cytotoxiciteit),

inflammatie, immuundysfunctie en verhoogde oxidatieve en nitrosatieve stress.

Los van de vraag of symptomen, zoals pijn etc, onverklaard ("psychosomatisch") zijn,

is vastgesteld dat mensen met wijd verspreide pijn een grotere kans op kanker hebben.

Een onderzoek van Jason en collega's onder een groep overleden ME/CVS-patiënten

wees uit dat deze mensen veel jonger door kanker, hartfalen en zelfmoord stierven

(24 jaar resp. 24 jaar en 8 jaar eerder) dan de gemiddelde Amerikaan(se).

Als de uitkomsten van deze kleine steekproef algemeen geldend zijn voor ME/CVS,

dan hebben deze observaties van Jason en collega's zeer verstrekkende gevolgen.

Causes of death among patients with chronic fatigue syndrome.

Health Care Women Int. 2006 Aug;27(7):615-26.

doi: 10.1080/07399330600803766.

Jason LA, Corradi K, Gress S, Williams S, Torres-Harding S.

Participants in this sample included individuals

who had been entered in the memorial list compiled by the National CFIDS Foundation.

This list included individuals with ME Chronic fatigue immune dysfunction (CFIDS)

who have died up to the summer of 2003.

The sample totaled 166,

with 164 reporting the sex of the individual,

145 reporting the cause of death of the individual, and

99 reporting the age of the individual.

The three most prevalent causes of death were heart failure, suicide, and cancer,

which accounted for 59.6% of all deaths.

The mean age of those who died from cancer and suicide

was 47.8 and 39.3 years, respectively,

which is considerably younger than

those who died from cancer and suicide in the general population.

The median age of death for cancer in the United States is 72.

... the average age of death for suicide in the United States is 48, and

the average age of heart failure is 83.1

versus an average age of 58.7 years for the CFS sample.

What this suggests is that those from this memorial list

who did die of cancer, suicide, and heart failure were considerable younger

than what would have been expected from the general population,

which means that CFS might have increased the risk of death for at least this sample.

Volledige tekst van het artikel:

http://www.theoneclickgroup.co.uk/documents/ME-CFS_docs/

Causes%20of%20Death%20-%20CFS%20Patients.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Jason%20Sterfgevallen%202006%20195.htm

Volgens een studie van Meeus en collega's zijn specifieke immunologische afwijkingen,

• disregulatie van het RNase L-afweersysteem,
• activatie van NF-κB, resulterend in

verstoorde apoptose (natuurlijke zelfdoding van cellen) en

verhoogde oxidatieve stress, en

• verminderde werking van NK cellen,

aanwezig in ME/CVS én in kanker geconstateerd.

Immunological similarities between cancer and chronic fatigue syndrome:

the common link to fatigue?

Anticancer Res. 2009 Nov;29(11):4717-26.

Meeus M, Mistiaen W, Lambrecht L, Nijs J.

Cancer and chronic fatigue syndrome (CFS)

are both characterised by fatigue and severe disability.

Besides fatigue,

certain aspects of immune dysfunctions appear to be present in both illnesses.

...

Abnormalities in ribonuclease (RNase) L and

hyperactivation of nuclear factor kappa beta (NF-κB)

are present in CFS and in prostate cancer.

Malfunctioning of natural killer (NK) cells

has long been recognised as an important factor

in the development and reoccurrence of cancer,

and has been documented repeatedly in CFS patients.

•  The dysregulation of the RNase L pathway,

•  hyperactive NF-κB

•  leading to disturbed apoptotic mechanisms and

•  oxidative stress or excessive nitric oxide, and

•  low NK activity

may play a role in the two diseases and

in the physiopathology of the common symptom fatigue.

However, in cancer the relation

between the immune dysfunctions and fatigue has been poorly studied.

Immunological abnormalities

such as a dysregulated RNase L pathway, hyperactive NF-κB,

increased oxidative stress and reduced NK cytotoxicity, among others,

are present in both diseases.

These anomalies may be part of the physiopathology

of some of the common complaints, such as fatigue.

Further studies to confirm the hypotheses given here are warranted.

Volledige tekst van het artikel:

http://ar.iiarjournals.org/content/29/11/4717.full.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Nijs%20Kanker%202009%20620.htm

Dat de NK-cellen (verantwoordelijk voor het uitschakelen van zieke cellen)

niet goed functioneren in ME/CVS is in diverse wetenschappelijke studies vastgesteld.

Dat dit op langere termijn speelt werd recent door Brenu en collega's aangetoond.

Longitudinal investigation of natural killer cells and cytokines in chronic fatigue syndrome/myalgic encephalomyelitis.

J Transl Med. 2012 May 9;10:88. doi: 10.1186/1479-5876-10-88.

Brenu EW, van Driel ML, Staines DR, Ashton KJ, Hardcastle SL, Keane J, Tajouri L, Peterson D, Ramos SB, Marshall-Gradisnik SM.

NK cytotoxic activity was significantly decreased in the CFS/ME patients at T1, T2 and T3

compared to the non-fatigued group.

Additionally, in comparison to the non-fatigued controls, the CFS/ME group had significantly lower numbers of CD56brightCD16-NK cells at both T1 and T2.

Volledige tekst van het artikel:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464733/pdf/1479-5876-10-88.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Afweersysteem%20NK%20cellen%202012%20983.htm

Mogelijk gaat er, al dan niet als gevolg van genetische afwijkingen,

iets mis in de communicatie tussen de "signalerende immuuncellen" en de NK-cellen.

Excess of activating killer cell immunoglobulin-like receptors and lack of HLA-Bw4 ligands: a two edged weapon in chronic fatigue syndrome.

Mol Med Report. 2011 May-Jun;4(3):535-40. doi: 10.3892/mmr.2011.447.

Pasi A, Bozzini S, Carlo-Stella N, Martinetti M, Bombardieri S, De Silvestri A, Salvaneschi L, Cuccia M.

Chronic fatigue syndrome (CFS) is an inflammatory disease of unknown aetiology.

Here, we analyzed the genomic polymorphism of

killer cell immunoglobulin-like receptors (KIRs) and their HLA class I cognate ligands

in patients with certified CFS.

An excess of KIR3DS1 was found in CFS patients with respect to controls,

as well as an increased frequency of the genotype missing KIR2DS5.

In the patients, a great proportion of KIR3DL1 and KIR3DS1 receptors

were found to be missing their HLA-Bw4Ile80 binding motif.

We hypothesize that an excess of KIR3DS1,

combined with an excess of ligand-free KIR3DL1 and KIR3DS1 receptors,

may hamper the clearance of a pathogen via NK cells,

thus favouring the chronicity of the infection.

It is, however, their specific interaction [of KIR, FT] with HLA ligands

that explains their potential involvement in the occurrence of immune-mediated disease,

in cancer progression, in the clearance of a pathogen, or in transplant engraftment.

Through the interaction between KIR-HLA,

NK cells represent the link between innate and adaptive.

Based on the results of the present study, we hypothesize that

the presence of the activating gene KIR3DS1 may confer susceptibility to CFS.

This appears to support a scenario in which the risk of developing CFS is,

through a series of events, dependent on the level of NK cell activation.

Volledige tekst van het artikel:

http://www.spandidos-publications.com/serveFile/mmr_4_3_535_PDF.pdf?type=article&article_id=mmr_4_3_535&item=PDF

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Genen%20Afweersysteem%202011%20846.htm

http://mecvswetenschap.wordpress.com/2012/07/15/

overmaat-aan-kirs-tekort-aan-hla-bw4-bij-cvs

Een grootschalig onderzoek van Chang, Warren en Engels liet zien dat mensen met ME/CVS een grote kans lijken te hebben op non-Hodkgin lymfoom (een vorm van lymfeklierkanker).

Chronic fatigue syndrome and subsequent risk of cancer among elderly US adults.

Cancer. 2012 Dec 1;118(23):5929-36. doi: 10.1002/cncr.27612.

Chang CM, Warren JL, Engels EA.

CFS was associated with an increased risk of non-Hodgkin lymphoma (NHL)

(OR = 1.29, 95% confidence interval [CI] = 1.16-1.43, P = 1.7 × 10(-6) ).

Among NHL subtypes,

CFS was associated with

diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61),

marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and

B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23).

Chronic immune activation or an infection associated with CFS

may play a role in explaining the increased risk of NHL.

Samenvatting van het artikel:

http://onlinelibrary.wiley.com/doi/10.1002/cncr.27612/abstract

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Gevolgen%20Kanker%202012%20996.htm

Genexpressie-onderzoek van Kerr en metgezellen en Gow en collega's laat zien dat

een belangrijk deel van de genen waarvan de eiwitproductie ("expressie") afwijkt,

in de genenbank (GenBank) in verband gebracht worden met kanker.

Gene profiling of patients with chronic fatigue syndrome/myalgic encephalomyelitis.

Curr Rheumatol Rep. 2008 Dec;10(6):482-91.

doi: 10.1007/s11926-008-0079-5.

Kerr JR.

Following two microarray studies,

we reported the differential expression of 88 human genes in patients with CFS;

85 of these genes were upregulated and 3 were downregulated.

The top functional categories of these 88 genes were

•  hematologic disease and function,

•  immunologic disease and function,

•  cancer,

•  cell death,

•  immune response, and

•  infection.

Samenvatting van het artikel:

http://rd.springer.com/article/10.1007/s11926-008-0079-5

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Kerr%20Gene%20Expression%202008%20486.htm

Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis.

J Infect Dis. 2008 Apr 15;197(8):1171-84. doi: 10.1086/533453.

Kerr JR, Petty R, Burke B, Gough J, Fear D, Sinclair LI, Mattey DL, Richards SC, Montgomery J, Baldwin DA, Kellam P, Harrison TJ, Griffin GE, Main J, Enlander D, Nutt DJ, Holgate ST.

We set out to determine the precise abnormalities of

gene expression in the blood of patients with CFS/ME.

Genes showing differential expression were further analyzed

in 55 patients with CFS/ME and 75 healthy blood donors,

using quantitative polymerase chain reaction.

Differential expression was confirmed for 88 genes;

85 were upregulated, and

3 were downregulated.

Highly represented functions were

•  hematological disease and function,

•  immunological disease and function,

•  cancer, cell

•  death,

•  immune response, and

•  infection.

Volledige tekst van het artikel:

http://jid.oxfordjournals.org/content/197/8/1171.full.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Kerr%20Subgroepen%202008%20416.htm

A gene signature for post-infectious chronic fatigue syndrome.

BMC Medical Genomics 2009, 2:38. doi:10.1186/1755-8794-2-38.

JW Gow, S Hagan, P Herzyk , C Cannon , PO Behan, A Chaudhuri.

Top 5 diseases/disorders associated with CFS patients.

Volledige tekst van het artikel:

http://www.biomedcentral.com/content/pdf/1755-8794-2-38.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Gow%20GenExpresssie%202009%20567.htm

Het feit dat Rituximab werkzaam lijkt te zijn in

ME/CVS én in bepaalde vormen van kanker (bijv. in non-Hodgkins lymfoom)

geeft aan dat de ziekmakende factoren elkaar deels lijken te overlappen.

Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study.

PLoS One. 2011;6(10):e26358. doi: 10.1371/journal.pone.0026358.

Fluge Ø, Bruland O, Risa K, Storstein A, Kristoffersen EK, Sapkota D, Næss H, Dahl O, Nyland H, Mella O.

Major or moderate overall response,

defined as lasting improvements in self-reported Fatigue score during follow-up,

was seen in 10 out of 15 patients (67%) in the Rituximab group and

in two out of 15 patients (13%) in the Placebo group (p=0.003).

These observations suggest that

B-cells play a significant role in the ongoing clinical features of CFS,

and provide clues to possible aetiological mechanisms.

During follow-up, the maximum changes in SF-36 scores (as compared to the baseline level)

were significantly different in favour of the Rituximab group,

for "physical health summary score" (p = 0.039), and

the subdimensions "physical function" (p = 0.014) and "bodily pain" (p = 0.005),

while there were trends for

difference for "general health" (p = 0.081) and "social function" (p = 0.081).

Volledige tekst van het artikel:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198463/pdf/pone.0026358.pdf

Toelichting en commentaar op het artikel:

http://www.hetalternatief.org/Afweersysteem%20Rituximab%202011%20920.htm

Los van de vraag of pijn etc. "onverklaarbaar" is of als "psychosomatisch" afgedaan wordt,

is uit onderzoek, dat Macfarlane en McBeth begin jaren 2000 uitgevoerd hebben, bekend

dat mensen met "wijd verspreide pijn" een grotere kans op kanker hebben.

Association of widespread body pain with an increased risk of cancer and reduced cancer survival: a prospective, population-based study.

Arthritis Rheum. 2003 Jun;48(6):1686-92. doi: 10.1002/art.10973.

McBeth J, Silman AJ, Macfarlane GJ.

This study has demonstrated that widespread pain reported in population surveys

is associated with

a substantial subsequent increased incidence of cancer and reduced cancer survival.

At present there are no satisfactory biologic explanations for this observation,

although several possible leads have been identified.

...

However, understanding whether

subjects with widespread pain are at an increased risk of

cancer onset and/or reduced cancer survival

is important in trying to understand the mechanism underlying the association.

...

[B]iologic factors seem the most likely explanation of

an association with both cancer onset and survival,

but the evidence for any single such factor is weak.

Subjects with widespread pain have

high levels of psychological distress and mental disorder.

However, overall, the evidence does not support

an association between these factors and

increased cancer onset or reduced survival.

Volledige tekst van het artikel:

http://onlinelibrary.wiley.com/doi/10.1002/art.10973/pdf

Widespread body pain and mortality: prospective population based study.

BMJ. 2001 Sep 22;323(7314):662-5. doi: 10.1136/bmj.323.7314.662.

Macfarlane GJ, McBeth J, Silman AJ.

During follow up mortality was

higher in people with regional pain

(mortality rate ratio 1.21, 95% confidence interval 1.01 to 1.44) and

widespread pain (1.31, 1.05 to 1.65)

than in those who reported no pain.

The excess mortality among people with regional and widespread pain

was almost entirely related to

deaths from cancer (1.55 (1.09 to 2.19) for regional pain and

2.07 (1.37 to 3.13) for widespread pain).

The excess cancer mortality remained

after exclusion of people in whom cancer

had been diagnosed before the original survey and

after adjustment for potential confounding factors.

There is an intriguing association

between the report of widespread pain and

subsequent death from cancer in the medium and long term.

This may have implications for

the long term follow up of

patients with "unexplained" widespread pain symptoms,

such as those with fibromyalgia.

Volledige tekst van het artikel:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC55925/pdf/662.pdf