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Autoimmune Diseases Caused by Bacteria?

Jonathan Edwards

"Gibberish"
Messages
5,256
The ligament inflammation seems to be due to T or NK cells getting activated there for no good reason. Nobody fully understands why ligaments are a good place for T cells to play but there is a likely story.

In all of the T cell related 'seronegative spondarthropathies' we see inflammation in the chosen T cell zone (1. mucosa, 2. skin, 3. gut) PLUS inflammation at ligament attachments and nail beds. Nail beds are attached to bone so are pretty similar to ligament attachments. But in the disease of the number 4. zone ('everywhere else') we also see inflammation at a very curious group of sites:

Ligament insertion again - but widespread up and down the spine and sacroiliac joints (alias 'ankylosing spondylitis')
Nail bed again
Aortic root
Iris attachment in the eye
Apex of lung
Caudal spinal root sheaths

These might seem all very different but many people have noted that they are all sites of tension where elastin is important. And there is a disease of elastic fibres that affects exactly the same places - called Marfan syndrome. So the idea is that what we looking at is T cells playing out at sites of high tensile stress. The possible link is that wherever there is tensile stress fibroblasts will secrete TGFbeta. This is an anti-inflammatory cytokine and it may be needed to prevent inflammation from dissolving the tissue and causing it to pull apart. However, TGFbeta also regulates the expression of HLA-B on cells and the clue to all these diseases is a link to HLA-B27. The suggestion is that under certain circumstances TGFbeta has a paradoxical inflammatory, or perhaps 'scarring' reaction effect by allowing T cell interactions that would normally be switched off by interactions with HLA-B. This would make sense for NK cell interactions but nobody knows exactly what is going wrong.

Ligament insertion inflammation (or 'enthesitis') can be helped symptomatically by anti-inflammatories like ibuprofen or diclofenac. But a much more powerful effect is seen with TNF inhibitors, which will often abolish symptoms completely. The down side of TNF inhibition is susceptibility to infection. This is not a problem in most cases but is serious for a few. So TNF inhibitors are only used if there is a very good justification.
 

MEMum

Senior Member
Messages
440
Thank you so much for all your informed input.

My daughter has improved several times on antibiotics.
Her main symptoms are brain fog and exhaustion. The Abx have improved her cognitive function and stamina enough to study for and take several A-level modules.

She has regularly had high ASO titres and in autumn 2012 was found to have autoantibodies to the pyruvate kinase receptors in the basal ganglia. (She has no tics/motor disturbance). She is now 20, and has 1.5 A levels.
I was so excited when I learnt that Professor Vincent was going to be talking at the Invest in ME conference 2014; and even more so when I was able to talk to her afterwards. Her comments were that it was unlikely to be the PK receptor antibodies causing the symptoms, but that there were others they could look for if they had any blood left.

So, at our next appt with Dr Bansal in June, more blood was taken and sent to the Oxford neuroimmune labs. Sadly, for some reason it appears to have been redirected to Queen's Square, but they have not received it. Dr Bansal has taken another sample which he is keeping in the fridge until he knows where to send it.

The reason that my daughter does not stay on antibiotics for longer than a few months is because of the gut side-effects
If there was a regimen to follow for x months to eradicate the streps then she would persist, but we don't know who to approach for this.

Given the number of patients with ME who regularly have sore throats, inflamed neck lymph glands does anyone know if ASO is tested/positive?

Thanks for any ideas you may have
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Dear MEMum,
It does not sound clinically as if your daughter has a strep related illness. Rheumatic fever only lasts a week or two. Sydenham's chorea produces characteristic signs. Your daughter may have met a strep and acquired antibodies but it does not seem likely to me that this has anything to do with her illness. I would be interested to know where the pyruvate kinase receptor antibodies were done and how normal ranges have been established. I am not familiar with this assay. I agree with Angela that they would not seem to be relevant to her symptoms.

I do not see any need to give long term antibiotic. For strep infection a couple of days of penicillin is probably enough. Streptococci do not, as far as I know linger around and cause trouble. I am wondering why you would be giving long term antibiotic since there is, as far as I now, no reason to? Was it a chance observation that she improved after some antibiotics?
 

msf

Senior Member
Messages
3,650
Thanks again for the time you took to reply, Prof. Edwards. I appreciate the fact that you actually try to explain what might be going on - in my experience many doctors are only comfortable telling you what (in their opinion) is not going on.
 

MEMum

Senior Member
Messages
440
Dear MEMum,
It does not sound clinically as if your daughter has a strep related illness. Rheumatic fever only lasts a week or two. Sydenham's chorea produces characteristic signs. Your daughter may have met a strep and acquired antibodies but it does not seem likely to me that this has anything to do with her illness. I would be interested to know where the pyruvate kinase receptor antibodies were done and how normal ranges have been established. I am not familiar with this assay. I agree with Angela that they would not seem to be relevant to her symptoms.

I do not see any need to give long term antibiotic. For strep infection a couple of days of penicillin is probably enough. Streptococci do not, as far as I know linger around and cause trouble. I am wondering why you would be giving long term antibiotic since there is, as far as I now, no reason to? Was it a chance observation that she improved after some antibiotics?

Hi Professor
The pyruvate kinase receptors were tested for at Oxford - I think the John Radcliffe labs.
The results sheet shows:
IgG Basal ganglia antibodies ABGA Western Immunoblotting - Positive
ABGA neuronal pyruvate kinase - Positive
The results for neuronal aldolase c and neuronal specific enolase were negative.
There were no units/normal range.

I think Dr Bansal had an inspirational moment, knowing that Amber had had repeated high ASO titres and had responded well previously to injected penicillin.

Will gather info on Abx and ASO and improvements and post that separately.

Thanks again

Deb
 

MEMum

Senior Member
Messages
440
Re the ABGAs I read somewhere that some of the glycolytic enzyme receptors are involved in the cortico thalamic loops re cognitive function, not just motor responses.

Back to Antibiotics and ASO
Early Jan 2012 A was put on benzathine benzyl penicillin i/m twice a week for 8 weeks. Over this period her ASO went from 400 (IU/ml) to 200.
Her cognitive function and stamina improved from c mid Feb and by early March she was able to have Maths sessions with a tutor. (Not very easy to join in class lessons having missed so much Maths. Geography easier to catch up)
Was on azithromycin Apr and May as she developed tonsillitis.(ASO 800 2 weeks before this)
A took and passed AS Maths and Geography, but improvement not sustained, despite having TonsillX as that was thought to be the source of lurking strep.

There was a similar improvement with Azithromycin in Nov -Feb 2012/3 and then again in 2014, this time with Clarithromycin. These have both been prescribed with an initial treament dose, with a follow up lower "maintenance dose".

Her maths tutor, who did not know Amber pre ME says that it is like teaching a different person. When she is on the Abx she grasps things quickly, when she is not, she cannot recall things she knew inside out a couple of months previously and would recommend a BTec as more suitable than A-levels.

Her latest ASO are 400-800

Amoxicillin,penicillinV and erythromycin are not effective.

The Abx do not make her completely better, but make a very significant improvement.

Thanks again
 

Daffodil

Senior Member
Messages
5,875
MEmum....my doctor switches antibiotics every 2 - 3 months to try to prevent too many gut problems. You can also take probiotics, Tasectan, etc..I think...
 

Jonathan Edwards

"Gibberish"
Messages
5,256
Thanks MEMum,
This is really puzzling but an important story. I have been reading about the PK antibodies and although they seem still to be a bit controversial in terms of reproducibility they do seem to be of real relevance to some clinical syndromes. If it is Oxford doing the tests then the quality control will be solid. It is interesting that Angela thought the antibodies were not causing the problem. Angela and I share scepticism about the 'molecular mimicry story' for autoimmunity but we both believe that infection can sometimes be involved in the onset of clinical autoimmune disease. My instinct tells me that the ASO antibodies are also a red herring but I cannot be sure. And the problem with antibodies to microbes is that they are really a measure of immunity not disease. So a falling titre from 400 to 200 may not be good and a later titre of 800 may not be bad. I have a feeling there is a connection between all these things but probably not the sort of connection that you will find in the textbooks. Dr Bansal is a very knowledgeable and committed clinical immunologist and I would respect his judgement on actually trying to sort things out for you. Angela is being very helpful with input into ME research and maybe we will actually get some firm answers with these antibodies one day.
 

MEMum

Senior Member
Messages
440
MEmum....my doctor switches antibiotics every 2 - 3 months to try to prevent too many gut problems. You can also take probiotics, Tasectan, etc..I think...
Hi Daffodil
Thanks for your reply. Which Abx do you switch between?

We have tried a few probiotics; are there any you would recommend?
The "gut expert" at the IiME conference in June recommended live yoghurt for someone on regular Abx as did another friend who is a Biomedical lecturer. (Apologies to the gut Professor I don't have the conference info to hand.)

Another Doc said that the Multibionta one had done well on Which tests. Presumably this is viability of good bacteria rather than effect on dodgy guts!

Tasectan sounds interesting, but wonder how it would be longer term.

Thanks again
 
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MEMum

Senior Member
Messages
440
Thanks MEMum,
This is really puzzling but an important story. I have been reading about the PK antibodies and although they seem still to be a bit controversial in terms of reproducibility they do seem to be of real relevance to some clinical syndromes. If it is Oxford doing the tests then the quality control will be solid. It is interesting that Angela thought the antibodies were not causing the problem. Angela and I share scepticism about the 'molecular mimicry story' for autoimmunity but we both believe that infection can sometimes be involved in the onset of clinical autoimmune disease. My instinct tells me that the ASO antibodies are also a red herring but I cannot be sure. And the problem with antibodies to microbes is that they are really a measure of immunity not disease. So a falling titre from 400 to 200 may not be good and a later titre of 800 may not be bad. I have a feeling there is a connection between all these things but probably not the sort of connection that you will find in the textbooks. Dr Bansal is a very knowledgeable and committed clinical immunologist and I would respect his judgement on actually trying to sort things out for you. Angela is being very helpful with input into ME research and maybe we will actually get some firm answers with these antibodies one day.

Yes Dr Bansal is definitely an approachable and knowledgeable Clinical Immunologist;as well as being very committed to the ME community.
He has tried a selection of treatments, but so far only the antibiotics have helped.
He would agree that ASO and basal ganglia receptor antibodies are not his 'area of expertise', and not frequently tested for in ME.
From his B cell work I think he reckons that polyclonal B cell activation is 'at work'. How this fits in with symptom improvement on antibiotics I don't know, but then I'm not an immunologist!
I appreciate that Professor Vincent is not a clinician, but does anyone know of clinicians or others working in this area?
Russell Dale used to be at UCL, working on ABGAs, but is now in Australia. Is there anyone carrying on similar work at UCL that you know of?
I was really pleased to see that the first few people with ME have had their initial Rituximab treatment in Norway towards the end of October.
Any idea when the UCL trial will start? That should probably be on a different thread...
Thanks again
 

Daffodil

Senior Member
Messages
5,875
Hi Daffodil
Thanks for your reply. Which Abx do you switch between?

We have tried a few probiotics; are there any you would recommend?
The "gut expert" at the IiME conference in June recommended live yoghurt for someone on regular Abx as did another friend who is a Biomedical lecturer. (Apologies to the gut Professor I don't have the conference info to hand.)

Another Doc said that the Multibionta one had done well on Which tests. Presumably this is viability of good bacteria rather than effect on dodgy guts!

Tasectan sounds interesting, but wonder how it would be longer term.

Thanks again
Hi Memum. I think the protocol my doctor is using is based on some of the most recent lyme protocols. I have taken minocycline, doxycycline, rifampin, azithromycin, rocephin, etc. My brain works very poorly so I would have to get out all my papers to see what I took when. I think I usually took 2 at a time, then was switched to something else. I think one would have to be under the care of a Lyme doctor.

It would also depend on if you tested positive for Bartonella, Borrelia, C. Pn, or what....

There are other protocols such as the Wheldon protocol for MS.

Personally, I cannot take probiotics because they give me diarrhea. Weaker ones seem to be OK, but I have no idea if they are even helping or making things worse. I have leaky gut, so wouldn't taking bacteria be a bad idea?? Just don;t know....

xoxox
 

Jonathan Edwards

"Gibberish"
Messages
5,256
I appreciate that Professor Vincent is not a clinician, but does anyone know of clinicians or others working in this area?
Russell Dale used to be at UCL, working on ABGAs, but is now in Australia. Is there anyone carrying on similar work at UCL that you know of?

There are physicians at UCL/Queen Square (National Hospital) treating neuro patients for autoantibody diseases with rituximab but I do not know names. So far there is no specific link up with the ME service.
 

xrunner

Senior Member
Messages
843
Location
Surrey
The "gut expert" at the IiME conference in June recommended live yoghurt for someone on regular Abx as did another friend who is a Biomedical lecturer. (Apologies to the gut Professor I don't have the conference info to hand.)
Hi @MEMum
I was on multiple antibiotics on and off for over three years. In my own case an ordinary yoghurt just wasn't good enough. I haven't a particularly sensitive gut but I would not have been able to cope without stronger probiotics. The ones that helped the most were VSL3 and Lactobacillus GG taken a few hours after each dose of antibiotics.
 
Messages
4
Bacteria could well be the foundation of the initial infection especially that carried by ticks. In the 1930's some Jewish doctors fled Germany and settled in the Midwest, to their surprise, American did not know about the relationship of the tick borne spirochete model of MS which was accepted in Europe so they continued to conduct their studies. One such scientist was Dr. Gabriel Steiner who settled in Ann Arbor, Michigan. In 1952 he wrote an article called "The Pathogenic Role of Spirochetes in the Etiology of Acute Plaques in MS". Eventually these types of studies were discredited by the MS society itself...talk about shooting themselves in the foot in my humble opinion.

Recent research is zeroing in on over active mast cells (Mast Cell Activation Disorder/Disease) as being the common denominator between many auto-immune diseases such as RA, Lupus, MS etc. but who's to say that the hyper active mast cells are not in fact triggered into their new role by bacteria (and those fearsome ticks carry far more bacteria than Spirochetes, I have just recovered from anaplasmosis..but that's another story) which can infiltrate the blood brain barrier?

When one is being tested for mast cell disease a required test is the urine methylhistamine evaluation. If your test number is above 200 (which meets the WHO criteria) then you are diagnosed with a mast cell disorder Interestingly if you have all the symptoms, (including multiple allergies and anaphylaxis that arrived out if the blue) but your tests results come back at exactly 200 or less, guess what your diagnosis is? Fibromyalgia (and we all know it is often, if not usually, accompanied by it's sister, CFS/ME).
 

MEMum

Senior Member
Messages
440
Hi @MEMum
I was on multiple antibiotics on and off for over three years. In my own case an ordinary yoghurt just wasn't good enough. I haven't a particularly sensitive gut but I would not have been able to cope without stronger probiotics. The ones that helped the most were VSL3 and Lactobacillus GG taken a few hours after each dose of antibiotics.

Thanks for this info, the VSL3 sound pricey, but if they work it would certainly be worth it.
 
Messages
15,786
Thanks for this info, the VSL3 sound pricey, but if they work it would certainly be worth it.
VSL#3 has been working well for me. I started it about two months prior to starting antibiotics, then continued taking it during 3 months of IV antibiotics and 2 months of oral antibiotcs so far. I haven't had any GI problems, and no diarrhea unless I eat Mexican take out for dinner :rolleyes:

A stool sample also showed that I completely lacked bifido bacteria prior to starting VSL#3, so presumably it's helping rectify that as well.
 

A.B.

Senior Member
Messages
3,780
The possibility that yersinia enterocolitica infection might become chronic was mentioned a few pages ago. Is it worth testing for this? In my family, three of us were infected by repeatedly eating contaminated eggs. Many years have passed but the same people now all have or had CFS like illness.

PS: we know for sure it were eggs because my dad worked in a hospital and had someone look at it. The strain I'm not 100% sure but it was some yersinia and the symptoms included gastrointestinal bleeding.
 
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knackers323

Senior Member
Messages
1,625
Ok as @Jonathan Edwards doesn't seem to have any idea why abx can help people feel better after only a day or two, I will ask this question.

Are the bacteria in the gut more susceptible to antibiotics than in other places in the body, and that's why they can have an effect so quickly?