Patient questions: Is mast cell disease autoimmune?

Autoimmune disease is when your body has an abnormal immune response to something that is a normal part of the body. There are more than eighty currently identified autoimmune diseases and they affect a significant population worldwide. At least 2% of women are estimated to have at least one autoimmune condition. Multiple sclerosis, rheumatoid arthritis and lupus are examples of autoimmune disease. Autoimmune diseases can affect small areas or multiple organs or targets throughout the body.

There are a number of possible causes of autoimmune disease. Some well supported theories include:
1. Molecular mimicry. This occurs when the body is exposed to an external danger and direct antibodies and immune defense against this danger. However, once the danger has been resolved, the antibodies and immune defense are directed toward damaging some normal part of the body that by happenstance looks like the dangerous thing. A classic example of this is development of rheumatic fever, PANDAS and other complications after a Streptococcus infection. The body makes antibodies to fight Strep, the Strep is killed and infection resolved, but the antibodies then attack things in the body that look like strep to the antibodies.
2. Genetic predisposition. Mutations and improper expression of genes that mediate tolerance, like HLA genes, can result in autoimmune disease. In these patients, these anomalies cause the body to fail to recognize itself as “safe”.
3. Cryptic determinants. This refers to the situation in which a hidden part of a normal structure in the body is not usually “seen” by the rest of the body. When that hidden part is exposed to the rest of the body, the immune system does not recognize it and attacks it, thinking it is dangerous. I imagine this as a waterway in a year of drought. A river has many small black rocks on the bottom. When the water is high, like most years, you cannot see these rocks. In a year of drought, the water level drops and you can the black rocks on the bottom. They were always a natural part of the riverbed, and they were always there, you just couldn’t see them. This can happen inside the body too. Sometimes your immune system sees things that were always there but not seen by it before.

The key feature unifying autoimmune diseases is that the immune system directly targets a part of the body that is normal and healthy. In lupus, the body makes antibodies that target the DNA inside our cells, which is not just normal but critically important to survival. It doesn’t target defective DNA, it targets regular old, keeps us alive, DNA.

Mast cell diseases are not autoimmune diseases. Mast cell diseases are not directly their attacks to a normal, healthy part of the body. In mast cell disease, mast cells are dysregulated and behave inappropriately. While this can damage parts of the body, this damage occurs due to the general inflammatory environment rather than because mast cells specifically targeted those parts of the body. Aberrant mast cells aren’t saying, “Quick, there’s an intruder in the liver! Let’s go get them!” when it’s just your regular liver hanging out. They are just so activated that mediator release could damage some cells in the liver, and in other places at the same time. The mast cell activation does not specifically target the liver in this scenario.

A confusing aspect of mast cell disease is that MCAS can occur secondary to autoimmune disease and many MCAS patients have autoimmune disease. In this patient population, the MCAS is probably induced by the inflammation caused by the autoimmune disease. Even still, while the primary autoimmune disease targets specific parts of the body, MCAS does not target specific parts of the body to attempt to destroy them.

14 Responses

  1. Yvonne July 9, 2016 / 12:13 pm

    Thank you for this clarification. I knew Mast Cell Disease was not an autoimmune problem, but until now did not understand why it wasn’t.

  2. Jana B July 9, 2016 / 8:35 pm

    Lisa, couple of questions…but first thank you for continuing to educate us! I have been diagnosed with MCAS, EDS-H, POTS, and Unspecified Diffuse Connective Tissue Disease. I have a positive ANA test, well several times it has been positive but it has also been negative. I also have had 12 Oligoclonal bands show in my CSF test that lead my neurologist to diagnose me with MS, but that has been overruled by other neuros. Therefore, my rheumatologist says I have an autoimmune disorder, but none of the specific antibodies show up for Lupus or Sjogren’s even though my symptoms are such and my dad and sister have them. So, she is calling it Unspecified Diffuse Connective Tissue Disease. I am being treated with Imuran and Plaquenil after my lungs had 100s of nodules on them and my kidneys were leaking protein and the kidney biopsy showed damage. Since treatment, both have resolved. 1) Do you think MCAS patients can have positive ANAs and/or positive lumbar punctures and only have MCAS, not an autoimmune disease? 2) Do you think MCAS can make 100s of lung nodules and/or cause kidney issues like leaking 100x the normal amount of protein? I’m asking you simply because I’m hoping you might know more than my current doctors! I would love to get off of the immunosuppressants if possible if I don’t necessarily have an autoimmune disease, but 3) I also wonder if immunosuppressants help MCAS? Thank you for your help!!!

    • Lisa Klimas July 10, 2016 / 1:45 am

      These are all great questions that require in depth answers so I will include in an upcoming “patient questions” post.

      • Jana B July 11, 2016 / 11:20 pm

        That would be so kind! Thank you very much! I appreciate ALL you do for us!!!

    • dkaj July 10, 2016 / 1:36 pm

      Jana, where did you find a doctor to help you with all of these tests and figure all of this out? I am trying to find/decide on where would be the best place to take my 10 y/o dd to finally get down to the underlying causes for treatment where someone will look at all of these same issues you are talking about, connective tissue, some orthostatic intolerance, Gi issues and etc.

      • Jana B July 11, 2016 / 11:28 pm

        D K A J, I live in North Texas, and there are three doctors who don’t office together, but who each specialize in different fields relating to my new diagnoses, and who are seeing a lot of the same patients and referring them to each other when warranted. One is a Cardiologist for POTS/Dysautonomia, another is an Allergist/Immunologist who is open to helping with Mast Cell, and one is a Geneticist for EDS. Lastly, unrelated to the other doctors is one for Rheumatology for the Autoimmune Connective Tissue Disease. Hope that helps! Best of luck to you and your daughter!

  3. Mark July 10, 2016 / 8:20 pm

    >Mast cell diseases are not autoimmune diseases.

    >A confusing aspect of mast cell disease is that MCAS can occur secondary to autoimmune disease and many MCAS patients have autoimmune disease. In this patient population, the MCAS is probably induced by the inflammation caused by the autoimmune disease. Even still, while the primary autoimmune disease targets specific parts of the body, MCAS does not target specific parts of the body to attempt to destroy them.

    Lisa, I’m afraid I don’t grasp what meaningful distinctions you are conveying, nor whatever supporting authority — in contrast to most of what you’ve prolifically marshalled, articulated.

    Why is it confusing autoimmunity can be the underlying cause of MCAS?

    Are you defining “mast cell disease” to exclude MCAS/D?

    How “secondary” other than some semantical choice/preference?

    MCAS probably induced by inflammation? Why? How would this be definitively determined?

    What would lead instead to determinations that MCAS is “Primary,” induces inflammation and/or autoimmunity?

    What establishes that “primary autoimmunity” attacks particular tissues, organs while MCAS does NOT?

    How would drs determine the opposite from determinations/surmises you assert here?

    What meaningful impact would result therefrom, as opposed to what you DO assert here?

    I have not encountered a sound scientific basis for a sweeping, divisive premise that seems to infuse, pervade, most everything here: A claim that the bases for systemic mediator afflictions in “Mastocytosis” v. in “MCAS” are utterly distinct? Hence, among other things, you would be contending precisely the opposite vis-a-vis autoimmune disease in all these respects for Mastocytosis v. MCAS? With what Dr. Akin called the “symptoms of mast cell degranulation commonly encountered” in SM? Widely understood, agreed, I thought, to be “clinically identical” to those suffering MCAD/S. Including under the MCAS “Consensus Proposal.”

    I could marshall various counterarguments, evidence. But since where these contentions come from, what they mean, I don’t want to volley blindly into the dark — not grasping what I’d be addressing.

    But one example: The NIH has been researching for years the underlying genetic alterations associated with “Idiopathic Anaphylaxis” — under a protocol including alike both patients diagnosed with Mastocytosis and patients not diagnosed with Masocytosis. Following, I believe, the groundbreaking genetic findings of Prof. Molderings/colleagues. When Dr. Metcalfe gave a preliminary report of the NIH findings to the AAAAI years ago, I believe his presentation likewise underscored no distinctions between subjects diagnosed with Mastocytosis v. not.

    • JD July 10, 2016 / 10:27 pm

      Mark, your tone here is disrespectful. It comes across as a pointed personal attack rather than a healthy debate. What’s the deal?

    • J July 11, 2016 / 12:56 am

      I second what JD noted. I do not believe your response was respectful Mark. It is also difficult to decipher quite what you are saying as it lacks clarity. Lisa spends an enormous amount of her time volunteering to help patients and summarize literature. If one wishes to have a healthy debate that’s one thing but if the intent is to merely mock her and take her down, go leave your nebulous comments elsewhere. She is reporting from peer reviewed journals, not pulling her information from thin air. This is science and this is an incredible person who gives so much to the community, be decent.

      • Mark July 12, 2016 / 2:44 am

        My post discussed nothing but medical matters. The insults, name-calling, etc. all devoid of medical content are abusive towards ME. I still see nothing suggesting how any question/comment I posted should be phrase instead — much less providing answers to what I had tried in good faith to foster productive medical discussion. I should have lept to conclusions about what I addressed and responded to surmise rather than trying, again in good faith, to grasp what had been posted and based on what — since no authorities were provided us and what I have encountered largely indicates the opposite of what I would guess was conveyed. I do not sink to insults, name-calling, posts devoid of medical content. I pose Qs out of respect when I am unsure about contentions, NOT wanting to leap to unfair conclusions. ??????????

  4. Lisa Klimas July 10, 2016 / 9:02 pm

    Of course I am not excluding MCAS from mast cell disease.

    It is confusing to many patients.

    I’m sorry that you feel the post is unclear.

    • Mark July 11, 2016 / 1:38 am

      What in my post fails to address substantive medical matters. The only personal attack I see is yours on me. Mentioning no medical matter addressed by me or anyone else, only an empty insult of me pointing to nothing I posted that crosses any such line. Can you enlighten me? How would any questioning of the medical matters I do be rephrased to strike you as less “personal.” I genuinely don’t understand what’s being asserted, on what basis. So I am left to ask, rather than leap to conclusions that might well be off. How is this disrespectful? I’m at a loss. I don’t read most of what’s posted here, despite my interest. I don’t recall a piece previously without references, as here. Again, how can I ascertain but by asking?

      ‘C’ findings for Aggressive SM by definition target organ function.Other findings with mastocytosis can involve organ damage, too — the distinction being articulated as not impairing organ function — a distinction I have never heard being described, applied coherently.

      • Jeff D July 12, 2016 / 1:59 am

        Mark – the problem is with your tone. You aggressively interrogate Lisa as though you are her superior sitting on her dissertation committee. You failed to address her with the respect one would give a colleague.

        There was nothing inherently wrong with the content of your post. Had you framed your content in a respectful manner, while treating Lisa as your equal, your post would have been fine.

        As it stands, you are now claiming that you do not understand what you did wrong. If you are truly as “at a loss” as you claim to be, then my recommendation to you is to sign up for a remedial social skills course offered by your local “Adult Education Center.”

      • Mark July 12, 2016 / 2:47 am

        There may be confusion here since the post I was replying to is not the one directly above from Lisa.

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