I am hoping somebody can explain HOW an autoimmune disease causes peripheral neuropathy?

I was recently diagnosed with rheumatoid arthritis by a positive rheumatoid factor and a positive anti-ccp. My ANA was negative and all other autoimmune tests were negative.

I have scoured the internet and this forum and I still do not understand how the two are connected? Is my immune system literally attacking my nerves? Is the inflammation causing the PN? What can I do about it or is there nothing that can be done? I am now taking methotrexate. Will treating the RA help the PN?

I feel so lost because I just don't understand what is happening to me and now my hands, in addition to my feet, are experiencing progressing PN. I don't understand my disease or what my future holds for me. I feel so hopeless.

Can somebody please explain?

Hi there,

So sorry you have had to join us as a result of your health problems. There are a few of us on here in the same situation. I have ankylosing spondylitis - an autoimmune rheumatic disease and more recently developed full body ( non length dependant) neuropathy. After so many appointments, it's still not entirely clear how this is happening and what the connection is. The inflammation from the RA could indeed be responsible but it may be a separate disease in its own right via a separate autoimmune mechanism. It's all so complicated. Controlling the RA may help but there's chance it won't. Often times a process is underway which may not be linked to the original autoimmune. I've spent two years trying to get a definitive answer on it but no neurologist or rheumatologist has been able to give me this.
Have you had the nerve tests? Emg, nerve conduction? Skin biopsy?
Have you tried steroids since this started?

autoimmune disease is when the body makes antibodies to an invader that has peptide sequences in its cell walls that resemble those of the antibodies. When the invader is gone, those antibodies for some reason linger and start attacking tissues of the host, and nerve tissue is often commonly attacked. In some people these antibodies do not shut off and the body continues to make them. It is thought that some autoimmune processes are inherited.

The vaccine for Lyme only caused attacks on hosts' joints, that carried certain markers on their white cells.

I used to have a very old cat..who had terrible arthritis...and our vet at the time told us that AUTOIMMUNE disease is
becoming epidemic in cats. (today our poor pets are vaccinated to death IMO) Pet vaccines were causing sarcomas in cats, so now they vaccinate in the leg...so if the sarcoma (cancer) occurs the vets can amputate the leg and save the cat. Some compassion? Think about that.

Infections can also trigger autoimmunity in those who have certain genetic markers making them at risk.

Historically rabies vaccines, have been the worst offenders, until that Lyme vaccine showed up. Even the newer rabies types have studies on PubMed about reactions. If you search
"rabies" on PN you will find the posters here over the years who have gone into detail about neurological reactions.

So today there is quite a bit of concern about too many vaccines. I am sure you could Google to find the process by which micro-organisms trigger autoimmunity, but the ones I have seen are very complex explanations and involve genetic data and terminology.

Adding a bit to what mrsD has explained:

Antibodies are made by blood cells called plasma cells which are produced from B lymphocytes (B cells). Each clone of B cells and plasma cells produces a unique kind of antibody.

Production of plasma cells needs help from a class of T lymphocytes called helper T cells. Helper T cells need to get activated before they can do their job. This happens when they recognise a complex of a peptide (a small part of a protein) bound to Class II MHC proteins on cells called antigen-presenting cells. There are many different kinds of Class II MHC proteins - everybody inherits a specific pattern of them from their parents.

Usually that peptide is derived from a protein made by a pathogen (virus, bacterium, etc). Most often clones of helper T cells get specifically activated by recognising a peptide:Class II MHC complex. They go on to activate specific clones of B cells with the same peptide:Class II MHC complex on their cell surfaces. The plasma cells derived from them secrete specific antibodies which lead to destruction of the pathogen which made the protein.

However, sometimes this goes wrong. A combination of pathogen peptide:Class II MHC protein might, in a chemical sense, "look like" a combination of normal body cell peptide:Class II MHC protein. The effect of this is that the immune system will damage the normal body cells which made that peptide, "thinking" that those cells are pathogens - this is an auto-immune disease.

Inheritance of a specific pattern of Class II MHC proteins is often a risk factor for specific auto-immune diseases. For example, inheritance of forms of a Class II MHC protein called HLA-DRB1 is a risk factor for RA. Presumably this is because complexes of pathogen peptide:HLA-DRB1 can "look like" complexes of joint tissue peptides and HLA-DRB1, leading to immune system damage of joint tissue.

I hope that this is not too complicated and makes sense.

Thank you for explaining. I was never very good at science or biology, so it's been a struggle trying to figure this out and wrap my mind around what is happening. I've never contemplated this side of me before. I guess until something goes wrong, you don't really question the process.

I just feel like I'm broken, or in the process of breaking apart, and nobody can do anything about it. I feel like every day I am just helplessly witnessing my own demise. Sometimes I reluctantly accept that and other times I have full breakdowns. I know it's all science and bodily chemistry, but sometimes I wonder what I did so wrong in life to end up here.

To answer you Joanna, I have an EMG coming up in August. I have not had a nerve biopsy done yet. I am more than certain at this point that I am dealing with a small fiber neuropathy, but my neurologist looked at me like I was an idiot when I said that. So I guess I will go through the EMG and hopefully at some point we can get to the nerve biopsy and the SFN can be confirmed. I am having an MRI on Wednesday to rule out MS, I assume. No steroids as of yet. So far just the anti-inflammatory and the methotrexate. I was expecting side effects from the mtx, but so far nothing. But joints still hurt like crazy but it's only been a few weeks of the meds.

I try really, really hard not to be a baby about it. I think about little children who are diagnosed with cancer and lose the fight. Sometimes when I want to cry about how unfair this feels, I am thankful that I least got to 30 relatively healthy and I enjoyed my twenties. If things have to fall apart now and I can't do anything about it, then I am glad to have enjoyed life to the extent that I have. This sounds somber and I apologize for that. More or less just realizing that what is happening is not going to go away and this is my life now. Out of all the pills and supplements I am taking, that reality is the hardest one to swallow.

Can anyone explain the relationship between autoimmunity and inflammation? I have SFN and "the antibody profile of a lupus patient" and am followed by a rheumie as well as neuro, but have no signs of inflammation in blood work, skin biopsy, or muscle biopsy. My CRP and sed rate are always at the low end of normal. Nothing but my ANA, anti-dsDna, and anti-Ro come up positive. Everything I read about autoimmune conditions seems to assume that there is inflammation.

Thanks for the explanation.
We have got some autoimmune disorders in our family, is it possible to test for the patterns of class II MHC ?


I hope your tests would point to a treatable cause.
The test for SFN is a skin biopsy and not a nerve biopsy.
And if your neurologist doesn’t take you seriously or doesn’t know enough about SFN maybe it would be better to search for a new neuro.
Only the 3rd neuro that I have met suggested SFN and referred me to the skin biopsy, which showed a severe damage. The other two, based on negative EMG, said I’ve got no neuro problems.
Don’t give up, it takes time to adjust to the new situation, find the right doctors, diagnosis and treatment.

Yes, it is possible - your health care team should be able to advise you about this.

However, please remember that different forms of Class II MHC proteins are just risk factors in the context of auto-immune diseases - they are not "genetic destiny". In my example above, some people with RA have not inherited the forms of HLA-DRB1 which are risk factors for it. Other people who have inherited those forms of HLA-DRB1 do not have RA.

--people with autoimmune diseases can see the effects, especially nerve effects, from several separate mechanisms, each acting individually or in concert.

A specific chemical attack on tissue, as kiwi has been describing, obviously can cause nerve damage. The body erroneously attacks its own tissue through chemical mechanisms by misidentifying it as foreign, and this process can literally dissolve functional parts of nerve. Often this is referred to as a "molecular mimicry" process--in vulnerable people, a pathogen of other foreign body may kick things off in that the body will mount an immune response to the pathogen, but since this is, on the most fundamental level, based on molecular shape (the body produces antibodies that fit into parts of the cellular structure of the pathogen, like manufacturing a key for a specific type of "lock"), if any body tissue have a similar shape, the now-activated immune system attacks anything that looks like such a "lock" and an autoimmune process ensues.

But, in addition to this, autoimmune attack typically results in swelling and fluid accumulation at the sites where this is ongoing. That swelling in itself can cause compressive forces on nerve, and nerves do not function well when constricted. So damage may occur in this way, in addition to and/or independently of the chemical damage.

This has sometimes been referred to as a "double crush hypothesis" in medical literature, with the symptomolgic effect more than what one would expect from the sum of the parts.

A lot of good information here. Thank you! Last night was a rough one, as you can tell, but I stayed up most of the night researching autoimmune diseases and what I have come to find true is that once an autoimmune disease occurs, the body is 3 times more likely to develop another one. Hence several existing at once. Right?

That got me looking at materials about "healing" the immune system. Leaky gut, toxins, infections, gluten and grains. What are your thoughts on this? Can the immune system really be healed through diet, fixing the gut, ridding toxins, and resolving existing infections? I found a few approaches that were very against medications such as NSAIDS and immunosuppressants and seemed to be very adamant that one can ditch medication and turn their immune system around, essentially switching "off" the genes that caused the immune system to turn against the body.

Any thoughts on this?