Hypothesized Causes of Rheumatoid Arthritis

Hypothesized Causes of Rheumatoid Arthritis

The causes of rheumatoid arthritis (RA) and most autoimmune diseases are unknown.[1] These related autoimmune diseases include celiac, type 1 diabetes, lupus, multiple sclerosis, and ulcerative colitis among others and they impact millions of people. That’s a sad thing since these diseases are insidious. Because of the lack of definitive information about the underlying causes of these diseases, there are many speculations running wild around the internet and unsuspecting sufferers look for answers from any place they can find it often leading to various home remedies.

Since being diagnosed with rheumatoid arthritis, my curiosity and scientific background pushed me deep into the research literature in order ferret out a cause for RA. While the research literature is somewhat sparse in this field, by far the most comprehensive work is from Dr. Alessio Fasano from the University of Maryland School of Medicine. He has an excellent article called “Surprises from Celiac Disease” published in the August 2009 issue of Scientific American.[2] While most of Fasano’s research is with celiac disease, a problem digesting the gluten protein in wheat, his work is beginning to shed light on the causes of other autoimmune diseases. He notes that a trio of triggers seems to be present and include 1. an environmental trigger, 2. a genetic susceptibility, and 3. a “leaky gut”.

With rheumatoid arthritis, scientists have long suspected that an infection of some sort, an environmental trigger, sets off the immune system to begin to attack the body’s own tissues. That’s why some of the early medicines, like sulphasalazine, were derived from antibiotics. Some still advocate long term antibiotic therapy for RA such as the Roadback Foundation which is devoted to advocating for antibiotic protocol for RA.[3] But infectious triggers have never been completely pinpointed nor fully used to explain the cause of the disease leading to widespread treatments.

Genetics also seem to be connected. Many people suffering from autoimmune diseases show a genetic marker for some type of histocompatibility leukocyte antigen (HLA).[4] HLA proteins bind to objects that they mistakenly recognize as foreign in the body.  This sets off an immune response where T lymphocytes recognize the object as “foreign”, call in reinforcements, and the immune system then fights the supposed “invaders” resulting in the body attacking it’s own tissue. During this process powerful inflammatory chemicals called cytokines are released. These cause the symptoms of RA and other autoimmune diseases. Cytokine receptors, like tumor necrosis factor (TNF), have been the target of RA research for the past 20 years and resulted in powerful RA drugs like Enbrel and Humira. A detailed description of these processes can be found at Johns Hopkin’s rheumatology website.[5] Some researchers propose that genetic switches may get turned on from certain environmental factors which then  trigger autoimmune processes to be initiated.[6]

But neither infection nor genetics fully explains a cause for rheumatoid arthritis. This leads to the third factor in the proposed trio of triggers – the so called “leaky gut”. This somewhat controversial trigger has been getting airplay in the internet for some time.[7] The prominent and highly interactive relationship between the immune system and the intestines is becoming clearer.[8] That makes sense because we ingest so many things into our bodies through our mouths. Our defense system must be ready to combat invaders. The intestines normally have a tight wall that keeps particles from leaking into the rest of the body. Dr. Fasano’s work with celiac patients is shedding light on how increased permeability of the intestines allows proteins to leak out into the body where they are immediately attacked by the immune system. The role of this in autoimmune diseases is speculative at this point and there is not a wide body of scientific research to completely support it. But some relief has been found in some people by controlling their diet – milk and wheat proteins being the most common. A variety of dietary changes may have an impact on inflammatory symptoms [ix] but there is not a generalized recommendation that all RA patients go gluten or lactose free as a treatment. Much more research needs to occur in order to determine what role, if any, the digestive/immune system connection plays in the processes of the disease.

There are many more questions than answers right now and the definitive causes of RA remains unknown. But there is work in this area and a quote from the Scientific American editors about Fasano’s article sums it up, “Surprisingly, essentially the same trio …seems to underlie other autoimmune disorders as well. This finding raises the possibility that new treatments for CD (celiacs) may also ameliorate other conditions.” This gives hope. Perhaps not for current patients directly since new and complicated medicines take many years to develop, test, and market. But there is hope for the millions of future sufferers of autoimmune disorders. The goal of such research into the causes of RA could potentially lead to better treatments and ultimately, a cure.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The RheumatoidArthritis.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.
View References
  1. http://www.nhs.uk/Conditions/Rheumatoid-arthritis/Pages/Causes.aspx
  2. Fasano A. Surprises from celiac disease. Sci Am. 2009;301:54-61.
  3. http://www.roadback.org/
  4. http://www.nejm.org/doi/full/10.1056/NEJMra1004965
  5. http://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-pathophysiology-2/
  6. http://www.ncbi.nlm.nih.gov/pubmed/21343899
[vii] http://www.webmd.com/digestive-disorders/features/leaky-gut-syndrome [viii] http://www.datapunk.net/uploads/microbiota_immune_reciprocal.pd [x] http://umm.edu/health/medical/altmed/condition/rheumatoid-arthritis


View Comments (11)
  • Mdevaux11
    3 years ago

    Loved the article! If a genetic factor switched on, why don’t they focus on switching the genetic factor off or suppressing it? I feel like the medicines are just band aids. I was misdiagnosed 4 times before a new primary care sent me to a rheumatologist. Looking back I’m certain my mom had RA but was never diagnosed. I worry about my kids, both have had digestive issues. Sometimes I wonder if pregnancy with my 2nd brought on RA, that’s when I noticed the unbearable fatigue that never went away.

  • LifenowwithRD
    3 years ago

    Very interesting information. I’ve had gut issues and food sensitivities for the better part of my 51 years. I also have Hashimotos thyroid, and now just recently RA was diagnosed. Seems my body really hates itself. I feel that the gut runs the whole show. I don’t know what caused it all with me as I was an avid runner pre-RA, ate real foods, watched out for the processed stuff and maintained a healthy weight, as well as sleeping 8-9 hrs a night, happy life, etc… I can’t figure out how this hit me but I am also a believer in genetic predisposition. I have parents with the thyroid issues, and a brother with RA and possibly others. Moral of my story here is that no matter how well you take care of yourself anything can and will happen. Just trying now to stay positive and not obscess about this mysterious disease called RA.

  • jan curtice
    3 years ago

    Hi Andrew,
    I always look forward to your postings. They are enlightening and thought-provoking. I have been told that RA can be triggered by physical trauma to the body, especially those back-related. The reason I was given was that the trauma could trigger changes with the genetic code in the spinal cord and/or trigger the autoimmune response. Would this fall under “environmental triggers” or baloney? Thanks! =^^=

  • Andrew Lumpe, PhD moderator author
    3 years ago

    Hi Jan, thanks for the kind words. I’ve heard the same thing about physical trauma but I don’t believe that there is scientific evidence yet for this. You’re correct that it would fall under environmental and also genetic triggers.

  • Jane Burbach
    4 years ago

    I have done some research on the gut issues and have found published scientific studies about using l. Casei as an adjunct to RA medical treatment. The studies showed it helped with inflammation and improved flares. It can be taken as a supplement and some yogurt has it. I found two in our small town grocery store – Chobani and Greek Gods. Both are greek yogurt. Anyway I am trying the yogurt, which I ate regularly anyway, just not those with this particular culture on the label. And will consider pill form next time I am in the city. I am experiencing an improvement after a burst dose of Medrol and then two weeks later a Medrol shot. Switching to Enbrel any day.

  • Cecilia Jankura
    5 years ago

    I have heard of all of these things you have mentioned but I liked seeing it all in one article in the way you have presented it. I think since I have got ra at age 57(2010) I have experimented with my diet (nothing new as I grew my own organic food for over 30 years) to see if there was any connection. so far not really. I have noticed that when I went off of the long term <5 mg dose prednisone, it was easy to lose weight by staying off of a lot of animal products and grains. however, I am still going through withdrawals from the prednisone – it has been a month. (too bad after a clear pain free year on orencia infusions. I have noticed that I don't tolerate dairy like I used to – no ice cream, yogurt or milk in coffee (switched to almond/coconut milk). that's all I can see that is food related. perhaps my carefully selected vitamin and herbal supplements have been helpful as well. I have few side effects – just the occasional flareup – pain and swelling in different joints. Most folks think I look 15 years younger than I am – I am thinking that the healthy dietary approach and gentle exercise has helped with this. if only it could cure the pain! One other non diet related factor is stress. and that is so relative! I am not as capable of maintaining activity without complete rest. whenever I push beyond that point, it has it's effect. what has been really helpful is to be driven whenever possible. driving is hard on the body in surprising ways! also, autoimmune diseases are rampant in my family on both sides. I am very convinced of the genetic factor! I am the first one we all know of with rheumatoid arthritis. that's it for now. thanks for the forum

  • Andrew Lumpe, PhD moderator author
    5 years ago

    Cecilia, thanks for the kind comments and I’m glad you found the article helpful. I agree that stress exacerbates symptoms.

  • Lucy
    5 years ago

    Thanks for the great article. Research on causes can possibly lead to better treatment options! I was diagnosed with RA at age 13 after several years of ‘gut’ issues – am now 56, so I have been dealing with this for a long time. The same thing recently happened to my oldest son at age 20. He is on Humira which is helping the RA and the diarrhea issues. My father always had digestive issues and was never diagnosed with any autoimmune diseases but had plently of symptoms. My youngest son was recently diagnosed with IBS and tried to talk to his pediatric gastroenterologist about the possible leaky gut issue, wanting to address it and not progress toward an autoimmune issue. She dismissed the idea and gave him a probiotic and told him to avoid triggers. Frustrating! I will speak to my rheumatologist about this.

  • Andrew Lumpe, PhD moderator author
    5 years ago

    Hi Lucy, Thanks for the kind word and glad you found the article interesting. There is a genetic propensity for autoimmune diseases to run in families. You should check out the book by Dr. Mark Pimentel at Cedars/Sinai called “A New IBS Solution.” His research into the causes of IBS led to the identification of what is called “small intestine bacterial overgrowth” or SIBO and an effective treatment. Some GI docs buy into and others ignore it.

  • Erica
    5 years ago

    I am not a person who generally likes to post or comment on internet sites but this article definitely intrigued me. I have had RA since I was around 2 years old and am now currently 26 years old. For many years I was told it was because of a genetic correlation with psoriasis (which my father has). About a month ago I was diagnosed with Crohn’s Disease which has been another blow to my life and a massive inconvenience and frustration. 2 chronic autoimmune diseases-what a lucky gal I am! Anyway, this article and the research being done regarding the correlation between RA and GI diseases definitely holds true in my case. Well, that’s all I have to add to this matter at this time 🙂

  • Andrew Lumpe, PhD moderator author
    5 years ago

    I’m so glad that you found the article interesting. I’m so sorry you’ve been battling RA since 2! Don’t let anyone say that arthritis is just for old people. My rheumy said that genetics plays a role and my mom had Hashimoto’s Disease (autoimmune thyroid), my grandma had psoriasis, and her brother had ankylosing spondylitis. I’ve also heard of people getting multiple autoimmune diseases. Take care and thanks for reading. Andrew

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