Een recente studie van Amit Saha,
Ron Davis en anderen heeft betrekking op een aantal essentiële
eigenschappen van rode-bloedcellen: vorm,
vervormbaarheid, 'vloeibaarheid' en bezinkingssnelheid.
Om de snelheid waarmee rode bloed-cellen zich verplaatsen binnen (kleine) haarvaten en
de vervormbaarheid te bepalen, werden de cellen in een 'kunstmatig haarvat' ingevoerd.
De rode-bloedcellen van ME/CVS-patiënten (diagnosecriteria onbekend)
- hadden langer tijd nodig om in het haarvat binnen te komen,
- verplaatsten zich minder snel door het haarvat en
- pasten zich qua grootte/vorm minder goed aan (afgenomen 'vervormbaarheid').
De bezinkingssnelheid van de rode bloed-cellen van patiënten was verminderd.
Tevens werden bij patiënten verhoogde concentraties oxidatieve stress vastgesteld.
Ook m.b.t. de vorm van de rode bloed-cellen werden verschillende afwijkingen vastgesteld.
Daarnaast werden verschillen werden m.b.t. de 'bloedklontering' geconstateerd.
Ondanks dit alles waren de hemoglobine-concentraties vergekijkbaar met de controlegroep.
De vraag is in hoeverre de auteurs op de hoogte waren van het werk van Les Simpson,
die lang, lang geleden belangrijk werk op het gebied van rode bloedcellen verricht geeft:
klik hier, hier,
hier en hier.
Die vraag zal wellicht beantwoord worden als het uitgebreide verslag verschijnt (bron: Saha).
Erythrocyte deformability as a potential biomarker for chronic fatigue syndrome.
Saha AK, Schmidt BR, Wilhelmy J, Nguyen V, Do J, Suja VC, Nemat-Gorgani M,
Ramasubramanian AK, Davis RW.
Blood. 2018; 132:4874. doi: https://doi.org/10.1182/blood-2018-99-117260
Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)
is arguably the last major disease we know almost nothing about.
It is a multi-systemic illness of unknown etiology
affecting millions of individuals worldwide,
with the capacity to persist for several years.
ME/CFS is characterized by disabling fatigue of at least 6 months,
accompanied serious fatigue and musculoskeletal pain,
in addition to impaired short-term memory or concentration, and
unrefreshing sleep or extended post-exertional.
While the etiology of the disease is still debated,
evidence suggest oxidative damage to immune and hematological systems
as one of the pathophysiological mechanisms of the disease.
Erythrocytes are potent scavengers of oxidative stress, and
their shape changes appreciably in response to oxidative stress and
certain inflammatory conditions including obesity and diabetes.
The shape of erythrocytes change from biconcave discoid to an ellipsoid
due shear flow in microcapillaries
that provides a larger specific surface area-to-volume ratio
for optimal microvascular perfusion and tissue oxygenation
establishing the importance
not only of total hematocrit but also of the capacity for large deformations in physiology.
Clinically, ME/CFS patients show normal arterial oxygen saturation
but nothing much is known about microvascular perfusion.
In this work, we tested the hypothesis that
the erythrocyte deformability in ME/CFS is adversely affected,
using a combination of biophysical and biochemical techniques.
We tested the deformability of RBCs using a high-throughput microfluidic device
which mimics blood flow through microcapillaries.
We perfused RBCs (suspension in plasma)
from ME/CFS patients and from age and sex matched healthy controls (n=9 pairs of donors)
through a high-throughput microfluidic platform of 5µm width and 3-5 µm height .
We recorded the movement of the cells at high speed (4000 fps) ,
followed by image analysis
to assess the following parameters:
entry time(time required by the cells to completely enter the test channels),
average transit velocity (velocity of the cells inside the test channels) and
elongation index (ratio of the major diameter before and after deformation in the test channel).
We observed that
RBCs from ME/CFS patients had higher entry time (~12%, p<0.0001),
lower average transit velocity (~17%, p<0.0001) and lower elongation index (~14%, p<0.0001)
as compared to RBCs from healthy controls.
Taken together, this data shows that
RBCs from ME/CFS patients have reduced deformability.
To corroborate our findings,
we also measured the erythrocyte sedimentation rate (ESR) for these donors
which show that the RBCs from ME/CFS patients had lower (~40%, p<0.01) sedimentation rates.
To understand the basis for differences in deformability,
we investigated the changes in the fluidity of the membrane
using a lateral diffusion assay using pyrenedecanoic acid (PDA), and
observed that RBCs from ME/CFS patients have lower membrane fluidity (~30%, p<0.01).
Apart from the fluidity, Zeta potential measurements showed that
ME/CFS patients had lower net negative surface charge
on the RBC plasma membrane (~18%, p<0.0001).
Higher levels of reactive oxygen species (ROS)
in RBCs from ME/CFS patients (~30%, p<0.008) were also observed,
as compared to healthy controls.
Using scanning electron microscopy (SEM), we also observed changes in RBC morphology
between ME/CFS patients and healthy controls (presence of different morphological subclasses
like biconcave disc, leptocyte, acanthocyte and burr cells;
area and aspect ratio; levels of RBC aggregation).
Despite these changes in RBC physiology,
the hemoglobin levels remained comparable between healthy donors and ME/CFS patients.
Finally, preliminary studies show that
RBCs from recovering ME/CFS patients do not show such differences in cellular physiology,
suggesting a connection between RBC deformability and disease severity.
http://www.bloodjournal.org/content/132/Suppl_1/4874
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