Deplete the B cells, stop high blood pressure

[Hutan]

There was an announcement on Australian ABC radio today that a Monash university team have found that autoimmunity is a significant cause of treatment resistant hypertension. (I think other teams have been working on this idea too).
'Furthermore, blocking antibody production by depletion of B cells, protects mice against the development of hypertension.'

It's interesting given that autoimmunity has been implicated in POTS and of course Fluge and Mella's theory about endothelial dysfunction. Hypertension is such a big money spinner for drug companies. Perhaps this will result in much more research that helps ME patients.

This, from the university website, gives some background.
http://www.med.monash.edu.au/pharmacology/docs/pharmacology-honours-projects-2016.pdf

UNDERSTANDING THE IMMUNE BASIS OF HYPERTENSION
Supervisor: A/Prof Grant Drummond, Prof Chris Sobey Location: Vascular Biology & Immunopharmacology Group

Department of Pharmacology Monash University, Clayton

Background: Hypertension is a major cause of heart failure, heart attacks and strokes. Over 4 million Australians have hypertension and alarmingly, in up to 50% of cases, the condition is not controlled by current medications. Recent research has led to the recognition that hypertension is associated with activation of the immune system and accumulation of leukocytes (e.g. T cells, B cells and macrophages) in organs such as the kidneys, arteries and brain. Such findings suggest that immune-modulating therapies – akin to those already used to treat autoimmune disease – could be employed to control high blood pressure, especially in patients who do not respond to current drugs. But first, we must develop a better understanding of the factors that modulate the immune system in hypertension, and the mechanisms by which activated leukocytes promote inflammation and damage to arteries, kidneys and the brain.

Project 1: Does the gut microbiome influence sensitivity to hypertension? Disturbances to the make-up of gut bacteria, caused by diet or drugs (e.g. antibiotics), can influence health and disease. Thus, we wish to explore the role of the gut microbiome in regulation of immunity during hypertension. In this project, the gut microbiome of healthy mice will be manipulated by feeding them specialized diets or by co-housing them with hypertensive mice (mice eat each other’s poo!) to determine whether their sensitivity to hypertension is altered.

Project 2: How do B cells and autoantibodies cause hypertension? Hypertension in humans is associated with raised levels of circulating antibodies. We have shown that this also occurs in mouse models and that these antibodies accumulate in the walls of arteries. Furthermore, blocking antibody production by depletion of B cells, protects mice against the development of hypertension. We now wish to determine the targets (i.e. antigens) of antibodies in the vessel wall and investigate how antibodies interact with leukocytes, particularly macrophages, to cause their activation and the subsequent release of cytokines that promote vascular inflammation and stiffening.

 

[Kyla]

Don't most ME patients have HYPOtension (low blood pressure)? As opposed to hypertension (high blood pressure)?

Still an interesting article. Just made me curious. I thought double-digit blood pressure was standard in ME.

 

[Hutan]

Don't most ME patients have HYPOtension (low blood pressure)?

True. That's why I put this under 'Other Health News'.

(I've always had low blood pressure and since the onset of ME I have POTS. However lately I've been getting spikes of high blood pressure e.g. after a shower; after standing on a tram to get to my doctor's office. I think the dysregulation of blood pressure and heart rates in ME is often more complicated than fits neatly in to a box labelled e.g. POTS).

I was interested that autoimmunity seems to be popping up as a proposed cause of disfunction quite often. And understanding better how disregulation of one kind happens (and can be treated) may throw light on disregulation of another kind in the same body tissue. Imagine if it turned out that a large chunk of the population with high blood pressure needed their B cells knocked out. We could expect to see a lot of work to develop safe, cheaper drugs to do that.

 

[alex3619]

Don't most ME patients have HYPOtension (low blood pressure)? As opposed to hypertension (high blood pressure)?

Quite a few also have both hypertension and orthostatic intolerance leading to sudden hypotension, just not chronic hypotension.

 

[halcyon]

Don't most ME patients have HYPOtension (low blood pressure)? As opposed to hypertension (high blood pressure)?

OI can also cause diastolic hypertension.

 

[funkyqueen]

OI can also cause diastolic hypertension.

@halcyon : i'll be thanksfull if you can tell me more about that !!
( i'm interesting in, because : i have severe ++++ OI ( unable to standing up more than 0 to 4 Min/24H), and my cardiologist found the diastolic hypertension abnormality. ( After, i read again what Dr Hyde/Dr Cheney wrote and it seems MEers /severe MEers have this diastolyc disfonction)


Anyhting else : my normal tension ( before ME, and the 5 first years of ME was ALWAYS 13?/80.
I often read the majority of MEers/Cfs have low tension, but it was not my case.
Then, when i took vasoconstrictor drugs, i 've done 6 TIA. As i have no doctor, i had to done 6 TIA to understand by myself it was the vasoconstrictor the guilty
but, since the 6 months after begining B cells depletion by RTX, it's the first time of my life that my tension is lower ( currently 12, 11 :-o ! I really do not understand that phenomenon, but, i just can constat that)
Maybe it is Ritux ?
Maybe it is 'cause i received 2 to 3 infusions per week of 1 liter of Nacl 0.9% ( so it help me - a lot- hadding me some blood volume, and , of course my heart have to work less )
Maybe its because of two both? ( B cell depletion AND infusions)?
But in my opinion, it is more thanks to nacl Infusions 2 to 3 times per week, ...too hard for me to try to explain my feeling, but i feel it like that

 

[halcyon]

@halcyon : i'll be thanksfull if you can tell me more about that !!

It's something that Dr. David Bell observed. See this or this. He seemed to think that this still reflected low blood volume:

Orthostatic diastolic hypertension is when the lower number reflects the
systemic resistance. When standing, the lower number rises to try to push
blood up into the brain. When this happens to an excess, even if the patient
has high blood pressure, a liter of saline will help given IV. The numbers
show hypovolemia.

Maybe it is 'cause i received 2 to 3 infusions per week of 1 liter of Nacl 0.9% ( so it help me - a lot- hadding me some blood volume, and , of course my heart have to work less )

This may have helped some, yes.

 

[funkyqueen]

It's something that Dr. David Bell observed. See this or this. He seemed to think that this still reflected low blood volume:



This may have helped some, yes.

Well, it is not that it just " help" me, lol, it just save my life ;-)
Thanks very much for your answer and links (y) @halcyon

 

[Hutan]

@funkyqueen - that's interesting.
Can I just check I have understood what you are saying?

So you had marginally high blood pressure in the first years of ME (130/80 or more) and very bad orthostatic intolerance. [edited]

When you took vasoconstrictor drugs you had some transient ischaemic attacks (mini-strokes) due to lack of blood to the brain.

6 months after starting rituximab to knock out your B cells, your blood pressure is lower (systolic down to 120 or 110). But you aren't sure if it is the rituximab and/or the saline infusions.

I would have thought that increasing your blood volume with the saline would increase your blood pressure. And so it is the rituximab reducing your blood pressure. But who knows.

Your experience raises the question - just how much of the benefit of the rituximab treatment is due to correcting orthostatic intolerance problems. How is your orthostatic intolerance now?

@Jonathan Edwards, have you noticed any impact on patients' blood pressures (lowering or better regulation) when treated with rituximab?

 

[funkyqueen]

@Hutan , yes , it is correct, you understand well
well, the 4/5 months after the beggining of Rtx 's protocole, my tension was still normal ( my normal, so 13./80) ( i guess, because i did not take her often). And i used to took some vasoconstrictor drugs ( zomig for my migraines and cluster headeach, and other vasoconstrictor by nose). In this period , i had yet my 2 to 3 infusions of Nacl 0.9% per week, but my tension up to 16?/1?? to 17?/1?? ( you can see dyastolic disfunction ;-) during 2 weeks.

When you have a rtx infusion, the nurse check your tension every 30 minutes ( 'cause Rtx made lower your tension, when you receive it)
but, what i want to said exactly is : since the 6th month after the begining, my tension are now slower ( and always now) than my usual normal ( 138/80) ( and that, it is the first time of my life)

For answering you, my OI is a little better, but i think it is thanks to my 2 to 3 Nacl 0.9% 1 liter /week.
Maybe i'm wrong, and it is more Rtx than Nacl 0.9% infusion, but i feel it like that...