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.
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.
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:
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.
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 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
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.
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.
1. Significance of prediagnostic thyroid antibodies in women with autoimmune thyroid disease. Hutfless S, Matos P, Talor MV, Caturegli P, Rose NR. The Journal of Clinical Endocrinology and Metabolism, 29 Jun 2011, 96(9):E1466-71 DOI: 10.1210/jc.2011-0228 PMID: 21715532 PMCID: PMC3167665,
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