Antibodies, part 1, Anti-TPO

This is part 1 in a series on anti bodies and auto immune thyreoditis. In this first part I will take a look at anti bodies in general and Anti-TPO in particular. I think you will be a little surprised at some of the findings. It’s maybe a little nerdy for some. But the main points are listed in the summary. 

This is a complex topic, and there is a lot of research going on. I will probably revise these posts as I learn more. 

Abstract

All anti bodies look the same, Y shaped. They differ only on the tips of the Y. That is where they bind onto specific anti genes. People without thyroid disease can also have low levels of anti bodies, particularly Anti-TPO and Anti-TG. But whether they GET a thyroid disease later, we don’t know. A study showed, that many women had anti bodies up to 7 years before they got symptoms (1).

All antibodies are produced within the thyroid itself by B lymphocytes. So if on has little or no thyroid, one does not have high levels of anti bodies.

TPO is an enzyme that takes part in the process where Iodide gets converted into Iodine. Iodine is the form the thyroid uses in it’s hormone production. TPO can get damaged by oxidative stress. Anti-TPO then gets produced against the damaged enzyme. Oxidative stress can  start as a result of Iodine deficiency. The process has started. 

Anti-TPO is not what causes the greatest damage to the thyroid. It’s B and T lymphocytes that do that. Plus a form of the TRAb anti body, the cleavage TRAb. That can cause cell death as well. I will write about that in part 3.

One can have high levels of Anti-TPO without the thyroid decreasing in size. We call everything Hashimotos, but that is not correct. Hashimotos is the AIDT that starts with a goiter. The thyroid gets infiltrated by B and T lymphocytes, and cannot function as it should. But it doesn’t atrophy. Whereas Ord’s does not start with a goiter, and the thyroid atrophies. I will write more about that in a later part in the series.

What are anti bodies?

The body produces anti bodies or immune globulins, to combat anti genes, substances that the body experience as foreign or dangerous. 

All anti bodies look alike. It’s an Y shaped glycol protein. The larger part of the anti body are shared by all anti bodies. There is just a small portion of it that is specific to that particular anti body, see illustration below. The areas on the Y’s tips are the variable parts. This is where they bind to the anti genes. The area on the anti gene where the anti body binds is called epitope. It’s like a lock and key.

Anti body

It’s particular b cells, b lymphocytes, that produce anti bodies. There are differences between anti bodies according to how they are produced.

Monoclonal anti bodies are produced by identical b lymphocytes all coming from one mother cell.

Polyclonal anti bodies are produced by different b lymphocytes. 

I include this info because it can have some bearing on the progression of thyroid disease. One finds thyroid anti bodies also in people without thyroid disease. But there can be a difference in the thyroid  anti bodies between  the “healthy” and the thyroid sick in that their anti bodies can be mono- or polyclonal. The same anti body, i.e. Anti-TG can be both mono- or polyclonal. I don’t think this is established, but something scientists are looking into. 

Here is a graph showing anti body levels in the various groups:

AT is auto immune thyroiditis, GD is Graves, DTC is differentiated carcinoma (cancer), NG is nodular goiter and N is healthy . From Werner and Ingbar's The thyroid, a fundemental and clinical text, 9th edition.

I am a little skeptical of the claim that healthy people have thyroid anti bodies. This study shows women having anti bodies 7 years before they became hypo thyroid (1). One tested Anti-TPO in 31% 5 to 7 years before diagnosis. At time of diagnosis this had increased to 57%. Anti TG increased from 18% 5 to 7 years before to 47% at time of diagnosis. TSHR increased from 2 to 55%. These were military women who had been tested over the years without having thyroid disease at the time.

But it can very well be, that thyroid healthy people have a small amount of thyroid anti bodies all through life without ever becoming hypo or hyper. 

HT is Hashimos, GD Graves, C is control group.

But of course, there might be people who have thyroid antibodies for years and years without them ever increasing. I haven’t find any studies that have followed people with low anti body levels  for many years, except for the one over. I find it a bit strange that I don’t see scientists discussing this.

It’s an interesting fact from this study, that none of the participants who later developed Hashimotos ever had any TRAb (TSH receptor Abs). After all, it’s not uncommon for us with Hashimotos to have blocking TRAb. I will get back to that in part 3. 

NB! It’s b lymphocytes inside the thyroid who produce all thyroid anti bodies. (2). 

There is no production of thyroid antibodies outside the thyroid. That is why the anti body levels decrease after thyroidectomy. One can have no anti body flare if one has little or no thyroid tissue.

This is very important in terms of Iodine supplementation. I have been told by an admin in a pretty Iodine phobic group Canadian thyroid group, that one can have anti body flares even with little or no thyroid tissue left. I have only a pea sized thyroid. myself. That supplementing with Iodine could be dangerous, that I could get a TRAb flare impacting my eyes or skin. NO , I CAN’T.  You don’t need to worry about anti bodies if you have little or no thyroid (2).

TPO molecule

TPO and Anti-TPO

We patients talk a lot about Anti-TPO. We often say, it makes the thyroid detoriate. Or that it eats up the thyroid. I have said it myself. But Anti-TPO does not in reality play such a big part in the destruction of the thyroid. One can have anti body levels for years and years without the thyroid decreasing in size. There are other parts of the immune defense that cause the greatest havoc. Anti -TPO mainly inhibits TPO’s activity. That is it’s main destructive influence. It can destroy  thyrocytes, the hormone producing entities. But Anti-TPO does not really destroy a lot of thyrocytes.  And It’s only the Anti-TPO in the AIDT sick that can cause this damage, not the Anti-TPO that healthy people can have.

One does not see a connection between the Anti-TPO levels and thyroid destruction.  But that does not mean, Anti-TPO does not play a part in the development of AIDT. And there is a connection between the Anti-TPO level and symptoms. High Anti-TPO and Anti-TG  levels mean more symptoms. (3) 

It is mainly B- and T lymphocytes that destroys the thyroid. They infiltrate the thyroid tissue and create great destruction and cell death. There is also a third group of TRAb, cleavage TRAb that also potentially cause cell death, with atrophy of the gland as a result. I will write more about that in part 3.

TPO is an enzyme that has two very important functions.

  • It participates in the oxidation of iodide into iodine, as you see from the name “peroxidase”.  
  • It takes part in the syntheses of thyroid hormones

So no wonder we get hypothyroid when this enzyme does not work as it should! 

The TPO molecule can hold a heme molecule. I find that interesting, that iron is at the heart of the process so to speak. 

The Iodine organification

Iodide must have an organic molecule, H2O2 added by TPO to turn into iodine, which is the form the body can utilize.

Dr. David Brownstein writes in his book, “Iodine, why you need it…” (4), that iodine deficiency and oxidative stress leads to damage to the TPO enzyme.  The calcium in the cell stimulates this oxidation process, whereas  δ-iodine acetone  and other iodized lipids act as a brake. The damage begins, according to Dr. Brownstein, when there is not enough iodine for these lipids, these fatty acids. The brake in the system weakens, and we get too much H2O2. This too high level of H2O2 can damage TPO.  When TPO is damaged, Anti-TPO is produced. The process has begun. 

As the process proceeds, we can get damage to the thyroglobulin. The result is anti bodies to the thyroglobulin, thyroglobulin-ab.

So it starts here. While I don’t think Iodine deficiency is the only cause of AIDT, it is certainly a major factor. 

TPO and thyroid hormone synthesis

As you can see from the image below, TPO also plays a key role in the  synthesis of thyroid hormones. It does two jobs. It attaches iodine atoms to the tyrosine inside the thyroglobulin,  iodination. This iodination leads to monoidionated tyrosine (MIT) and diiodinated tyrosine (DIT). MIT and DIT are then attached to each other to make T4 and T3.  DIT+DIT for T4 and DIT+MIT for T3. This attaching together is facilitated by TPO .  

You see it in the figure below, where 2 DITs are combined to make 1 T4 molecule. 

In my endocrine textbook, it says, that there is even a little Reverse T3 produced in the gland. This was a surprise for me, I thought RT3 was made only out in the body tissue. I don’t feel a 100% sure about this.  

Taken from vivo colostate edu. (7)

Oxidative stress

Oxidative stress plays a large part in the development of AIDT. Hydrogen Peroxide is only one oxidant damaging our thyroid. Oxidants are parts of the oxygen molecule. They are a result of the metabolism in the cells (5). They are called ROS; reactive oxygen species.   

ROS include hydrogen peroxide(H2O2), hydroxyl radicals(OH2), superoxide anions(O2) and lipid peroxides. Anti-Oxidants protects the cell from oxidative stress under normal conditions. But the balance is not always kept, and one considers oxidative stress to be the cause of many diseases. 

mROS is ROS which originates in the mitochondria.

Anti-TPO and pregnancy

Anti-TPO can cross the placenta, but one doesn’t know yet if it cause harm to the fetus. Many women with AIDT have healthy children. The most important thing is having optimal thyroid levels, from day 1. And sufficient Iodine. Iodine is extremely important for the fetus’ cognitive development. 

References

2. Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Elenore Frölich and Richard Wahl. https://dx.doi.org/10.3389%2Ffimmu.2017.00521

3.  Autoimmunity affects health-related quality of life in patients with Hashimoto’s thyroiditis.  Uysal and Ayhan. https://www.sciencedirect.com/science/article/pii/S1607551X16301152

4. Dr. David Brownstein, “Iodine, why you need it, why you can’t live without it”. 5th edition, s. 106-108.

5. How one TSH receptor antibody induces thyrocyte proliferation while another induces apoptosis. Morshed, MA, Latif og Davies, 2013. doi 10.1016/j.jaut.2013.07.009

6. Environmental triggers of autoimmune thyroiditis. C.Lynne Burke, Monica V Taylor, http://Environmental triggers of autoimmune thyroiditis 

7. Synthesis and Secretion of Thyroid Hormones, vivo colostate.edu, http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html

8 Comments

  1. Lucie

    Hi, thank you for the information you put out there. I’m not sure if I misunderstood your research. Why though would my TPO levels shoot up from 4 to 44 upon starting iodine (20 mg daily) one month ago? Is it reversible? Thank you,
    Lucie

    • L S-L

      Hi Lucie!
      I can’ tell you if you will be able to reverse it. But I can tell you how to. Starting on such a mega dose is very unwise. You don’t share anything about your thyroid status, so I will just assume, you don’t have a thyroid disease. Anti-TPO of 44 isn’t high, though it might look like that to you. But you need to do something about it, as it can increase. Stop all iodine for now. Take selenium and drop gluten for some months. Gluten triggers anti-TPO. If you eat anti inflammatory food, that can only help. You can look at my post, Reducing antibodiesTake a new test after maybe 3 months. After some time, you can start supplementing iodine again, but in very small doses. And you need to test for anti thyroglobulin. That’s the thyroid antibody that can increase the most with high doses of iodine. Before taking any more iodine, please read my post on safe supplementation with iodine, Iodine for beginners.

      Do not listen to people in the iodine groups. They really don’t know what they are talking about. I have seen so many in these groups giving themselves a thyroid disease.

      All the best, Liv

      • Lucie

        Thank you, Liv! Appreciate the advice and will follow. No thyroid disease. Was actually following the advice of Dr Brownstein (who said somewhere the rise in antibodies is an expected transient response.). But am too anxious to continue at his recommended dose. Best wishes to you, Lucie

        • L S-L

          That’s good, Lucie. I have a great respect for Dr. Brownstein and all he has done to raise awareness about iodine. And how important it is for the body. But I do think, that he and his followers dismiss the dangers of high dose iodine. Whenever people complain, that they have gotten hypo or hyper thyroid in those iodine groups. It’s always the same, the admins ask, did you do the full protocol? did you take the Vit C, the B3 bla bla bla. As if some vitamine C will protect against all negative effects of starting high doses of iodine. And then, if the person hasn’t done absolutely EVERYTHING , it’s dismissed as just because of that. But it’s not. And it’s especially risky for people with no thyroid disease or even worse, are in the beginning of an AITD. I have stopped commenting in iodine groups. They don’t want to hear it. But I must have read more than 50 studies on iodine by now. And I share my insights here on the blog, and try to warn people the best I can. Don’t get me wrong. I love my iodine. But you have got to read up and take it in a safe way.

          I don’t think Dr B has said that you can get a transient rise in antibodies. He says, you can get a transient rise in TSH, not antibodies.

          Liv

          • Lucie

            You’re correct, that was my mistake. I was taking the higher iodine dose for fibrocystic breast disease and it really was working. Do you have an opinion on topical iodine as an alternative – or is that woo-woo?! (about to check if there’s a function on your site to buy you a coffee for all this invaluable free advice!)

          • L S-L

            Hi again!

            I have never even thought about adding such a button, but I have now. But honestly, you are the first person to offer to give me something. Thank you for that. Many don’t even say thank you actually.

            The fact that you have fibrocytic breasts tells me, you are iodine deficient. But the fact that your anti-TPO increased also tells me, you are prone to autoimmunity. So you need to do things thoughtfully. You don’t want to have healthy breasts, but a thyroid disease. Topical is the same as ingesting orally. The iodine will reach your blood stream. I would take my time, start low and increase over time if anti-bodies fell again. Right now it’s important to get your antibodies down. That you don’t get autoimmune thyroiditis.

            It’s very important to get IODINE for the breasts. Not only IODIDE. Lugol’s contain both, but is very high dose. So find something weaker to begin with. Sea weed products also contain both kinds, but can be more unsafe as far as how much they contain. But there are products out there. Even smaller doses of 200 to 300 mcg will help your fibroids over time.

            Best of luck, Liv

  2. Mouad

    I want to ask if strangulation can cause low levels of anti-tg and anti-tpo

    • L S-L

      Hi Mouad!

      This is not something I have thought about, but now I have looked into it, and yes, I think it can. There are several studies on strangulation causing thyroid storm. We all have 3 months supply of hormone in our thyroids. When the thyroid gets damaged in some way, large amount of hormone can leak out. And cause a storm of hormones, that is thyrotoxicosis. Dangerously high thyroid levels. Once there is damage to the thyroid, B- and T lymphocytes can enter the thyroid. These would be the cells producing anti-TPO and anti-TG. That would be a major damage. But I can imagne, that strangulation can also cause lesser damage, but damage big enough for lymphocytes to penetrate. There should be none of these lymphycytes inside the thyroid.

      This is an older study where they measured thyroglobulin in the blood of people dying from strangulation. They found elevated levels of thyroglobulin, . Indicating damage to the thyroid. If you read my post on thyroglobulin, you will see, thyroglobulin should be only inside the gland. We can have low, under cutoff point levels without it being a problem. But higher levels indicate damage to the thyroid, and then these lymphocytes penetrate and create the ANTI thyroglobulin. You can request the full text article as a patient, if you want to.

      I get a little worried when I see your email adress. If choking is something you engage in, I hope you take this on board. And I mean, worse can happen as well. One can die by accident.If you yourself now have some anti-TPO and anti-TG, please read my post For the thyroid newbie. Under “Odds and Ends”, I also have info on laser treatment of the thyroid. One has gotten good results with laser treatment in the early stages of autoimmune thyroid disease. It’s not something one can get done where I live. But in the US, it is possible. I think there is a clinik that does it in London as well. It’s a pretty simple laser procedure. I think one can find some videoes on YouTube.

      Blessings, Liv

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