If I had to choose just one thing to take from this conference, this would be it, because my entire understanding of autoimmune disease has just shifted ever so slightly on its axis, but in a really profound way.” Robyn Puglia
Many have described this year’s IFM Annual Conference on Autoimmunity as one of the best they’ve ever attended; packed to the brim with clinical insights and the very latest research from world renowned experts in their field. Robyn Puglia & Rachel Bartholomew both attended the prestigious functional medicine masterclasses on Autoimmunity in Florida earlier this year and recently got together to chat about their highlights.
“There’s so much intensive learning happens in just a few days like this, yet it’s vital to reflect on how you can apply this to your own clinical practice to directly improve your patients’ health.” Rachel Bartholomew
So their aim, when they sat down together for a ‘post-conference chat’ was to pick out a few clinical highlights. As they quickly realised, it’s almost impossible to narrow it down when the calibre of speakers is this good; they could have chatted for days on the subject!
RB - So the first, and is it fair to say your biggest highlight Robyn, came from one of the early talks by Dr Robert Rountree and Richard Mayfield on Toxicants & Autoimmunity?
RP – Yes definitely; one of the things I love about the conference is that it helps me to join dots between facts that I already know. The way that my brain works is that I'm really good at zooming in on detail, and the conference really helped me to zoom out a lot, and put facts that I already knew into a much bigger context. So with the Rountree and Mayfield talk, that was one of the things that happened…
Rountree and Mayfield talked about the role of hormones in the risk of autoimmunity, and the finding that 16 (OH) oestrogen metabolites have a really strong correlation with autoimmune disease; elevated levels of 16 (OH) metabolites have been found in the synovial fluid of patients with rheumatoid arthritis (RA). So, this is something that we’ve known for a while, and something that I’ve taught myself to nutrition students, but I hadn’t then taken the logical step forwards from that and asked, ‘so what are the ramifications of that? And what does that tell us about the way the body works?’
So what we’re talking about is a metabolite, or an alteration, and the reason that 16 OH is considered to be problematic, (and again this is something we’re all taught very early on in our nutrition training) is because, as a progression of that pathway, it creates quinones and has the ability to damage DNA, and that creates an increased risk of cancer, and breast cancer. However, Dr Rountree then followed with, “so what if the immune system is not actually reacting to self-tissue, but is reacting to damaged self?” And this was a real lightbulb moment for me. For years, I’ve been using all the accepted parlance when talking or writing about autoimmunity; “you’ve lost tolerance”, “your immune system is mis-reacting”, “your immune system is mis-responding”, “it’s an aberrant response”. I use all of those phrases, and I suddenly had this ‘aha’ moment; the immune system isn’t making a mistake, the immune system is actually doing exactly what it’s supposed to do, it’s not an aberrant response, it’s not a mis-response, it’s not a mistake, it’s doing exactly what it’s supposed to be doing, and reacting to something foreign in our bodies, and we need to remember that the thing that’s now foreign used to be self and that’s how this happens.
That was my big takeaway. And if I had to choose just one thing to take from this conference, that would be it, because my entire understanding of autoimmune disease just shifted ever so slightly on its axis, but in a really profound way.
So then I’m like, ok, let’s just roll that ball a little bit further, let’s think about what changes our proteins once they’ve been assembled? What is it that causes this post-translational protein modification? And there’s lots of things that do that actually:
Citrullination - this is where arginine in a protein is replaced with citrulline, and from an immunological perspective, this changes the protein from self to non-self, and there’s lots of things that can do that do a protein.
Bob Rountree mentioned passive smoking as a big risk factor for autoimmunity; and we know that smoking / passive smoking causes citrullination. We need to be thinking about whether a child grew up in a home where the parents smoked for example, and of course in our patient population, we are dealing with a generation where that was the social norm.
RB – Absolutely, and it’s not that long ago. I remember being in smoky restaurants and pubs, and the option of smoking or non-smoking seats on a plane - and this might have just been one row difference! It’s hard to believe that was the norm, and important to remember it’s not that long ago. We need to consider how smoking / passive smoking, either currently or in the past, might be affecting our patients’ health today.
RP – Yes, as if there was some kind on invisible barrier between those two rows on the plane! I can remember clearly when smoking was banned in restaurants and pubs, it being a big moment of relief for me; being able to go out for a meal without being exposed to passive smoke.
RB – So, it’s important when we’re thinking about autoimmunity, to remember that our generation grew up in an era when smoking was socially acceptable, and that passive smoking was also much more of a factor than it is today. And when taking a case history, you need to find out if this is a part of your patient’s story, either now or when they were younger.
RP – Yes, and there are lots of other things that can cause citrullination, not just smoking; Epstein Barr Virus and environmental toxins such as persistent organic pollutants (POPs) can do that too. Citrullination can also happen in an inflamed system as part of the production of arginine by the nitric oxide synthase enzyme. Citrullination is actually a relatively common occurrence in the body, and when it happens we call this a citrullinated protein, and one of the fairly well understood antibodies that we test for in autoimmune disease is anti-CCP, which of course is anti-citrullinated protein.
So that’s one way that proteins are modified after they are made but there’s actually many more…
RB – …and when you say, ‘that’s one way … and there’s actually many more’, this highlights just how vulnerable our proteins are to being altered, or damaged, and then to the ensuing cascade that can progress to autoimmune disease. And when you look at how prevalent those few things are that you’ve mentioned (passive smoking, inflammation, EBV) that can cause citrullination, it’s easy to understand why we are now facing epidemic levels of autoimmune disease. The points which you’ve just mentioned are just small pieces of the puzzle, and yet we can all relate to that; we’ve all been passive smokers at some point in our lives, and all of our clients can relate to that too, it’s a wonder that any of us are actually ok!
RP – Yes, it’s a real miracle actually! And when you start to think about it in even more detail, it becomes a bit mind-boggling! There’s also glycation; we talk about glycated haemoglobin all the time, what’s that? It’s a damaged protein; a changed protein. There’s protein oxidation and DNA oxidation too. Another marker we can test for is 8-hydroxy-deoxyguanosine (8-OHdG) – and that’s oxidised (or damaged) DNA.
RB – Do you have any ‘go-to’ tests for these markers?
RP - I test for oxidative stress markers in most of my patients; the most common of which are 8-OHdG and lipid peroxides. There are so many tests to choose from; but what you’re looking for is an ‘oxidative stress panel’, or for ‘oxidative stress markers’ to be reported on a comprehensive test. Some of the Doctor’s Data tests include these in their panels. I run some tests more than others, but we are so lucky in the UK because there is such a broad range of tests available and that’s just not true of most other countries. We have access to some really good labs, not just the ones that are here in the UK such as BioLabs (who I think are brilliant by the way) but Regenerus Laboratories allows us to access tests from the US, Germany etc. so you can cherry pick which panels you want for any given patient. Definitely though, when you are working someone up for autoimmunity, you need to be looking for antibodies and oxidative stress markers.
RB – Is there a single test you would recommend as a good starting point for looking at oxidative stress, for practitioners less familiar with these tests?
RP – Yes, Doctor’s Data (Regenerus Laboratories) do a good oxidative stress panel and they’re also bringing out a new test that will look at amino acids, red blood cell fatty acids, oxidative stress markers and red blood cell toxins, so that’s coming soon. And one of the other panels I use a lot is NutrEval (Genova Diagnostics) which is more expensive but very comprehensive. Even just starting with organic acids and blood chemistry can give you a lot of usable information. In a comprehensive blood chemistry test you can see oxidative stress markers such as uric acid, lots of inflammatory markers; ferritin (an acute phase protein), CRP, ESR, glycated haemoglobin (HbA1C) and white blood cell markers, which are important if you’re investigating autoimmune disease. Does it look like someone has a virus / bacterial issue / parasitic infection? Is the immune system suppressed? Is it upregulated? So, just a simple blood chemistry can be really useful. And of course then it’s important to look at all of the variables; diet and lifestyle imbalances, gut ecology and the microbiome, viral and bacterial infections, hormones, have they been taking the contraceptive pill? Did they take Roaccutane because they had acne as a teenager? What drugs have they been taking? If they have an autoimmune disease, have they been taking a drug where the consequences of that are actually more disruptive to the immune system? What chemicals have they been exposed to? Ionising radiation? And of course, psychological and relational stress is also a really big factor…
RB – …There is so much to consider with each individual patient, and that ties in really nicely with the message that came from Dr Deborah Bain in the presentation, ‘Changing the trajectory of autoimmune disease in children: Recognising patterns and enlisting a team.’ And this presentation highlighted how important it is to carefully gather together a comprehensive case history from your patients, and to look much deeper than just the immediate medical history of the patient sat in front of you. You need to enquire about the health of parents, siblings, grandparents, aunts, uncles and cousins to identify any patterns emerging that might give some clue as to what is happening for your patient. You could easily gloss over this as a clinician with only limited questions, perhaps just asking whether parents were susceptible to any illnesses in particular, and this presentation reinforced how important it is to look way beyond that and do as much digging through the family medical history as you can. This ‘gathering info’ part of a consultation is absolutely crucial, and makes us much better clinicians when we do it thoroughly, and with care and attention to detail. It’s so important to take time with your patients and really listen to their story.
RP – Yes, so looking at the child or adult sat in front of you - we need to be really looking at the whole family (parents, siblings, aunts, uncles, cousins and grandparents). And with children and young adults this is so important, because what we’re talking about is early identification, and prevention for the next generation, and intervention before a diagnosis. So you’re looking for patterns…so if someone comes to see you with a child with eczema, or a bald patch, or is bed wetting, or perhaps a teenager with headaches or migraines, or menstrual pain; essentially what you’re looking for is vague symptoms that might just indicate immune dysfunction or inflammation…which of course doesn’t necessarily lead to auto-immune disease, but if you have that in a child, adolescent or young adult, where there is a family pattern of significant immune dysregulation and auto immune disease, that child, adolescent or young adult is at a really high risk of developing auto immune disease, so you’re not just looking at what’s presenting, but what the consequences of that might be, given the genetic background. That’s super powerful; it goes way beyond just doing a stool analysis and tidying up the gut…
RB – Yes, recognising the pattern of the ‘evolution of an immune system in trouble’, or ‘the perfect storm’ as Deborah Bain described it. And she also made the valid point of how important it is to look beyond a diagnosis too. She said, “all that looks autoimmune may not be…” and then presented a fascinating case history of a young girl diagnosed with Hashimoto’s Thyroiditis who had experienced sudden hair loss but had no significant family history of autoimmune disease. She was unsuccessfully treated by medical specialists in dermatology and endocrinology, none of whom had uncovered the most significant part of her case history which was that she was a very driven high achiever, gaining straight A’s and was in the middle of a pressured musical theatre environment, very stressed and not eating properly when the sudden hair loss happened. Working from a functional medicine perspective, taking a detailed case history and using extensive functional testing, Deborah Bain found that she didn’t have autoimmune thyroiditis and secondary alopecia, and that consideration of a new hypothesis was needed. She was stressed to the max, had adrenal fatigue and needed adrenal and optimal nutrient support. After two months of supporting her in line with this new hypothesis, her thyroid antibodies normalised, she didn’t need any medications, and her hair was already starting to grow back. So, looking beyond a diagnosis is crucial.
RP – And I think that’s a really valid point to consider, once someone has been diagnosed with autoimmune disease, or has been given a label, the questioning sometimes stops there as far as conventional medicine goes, and every symptom thereafter is accounted for via the label that they have; “…well of course you have problems with your gut, you’re coeliac”.
“And this is a failure of the conventional system because there is often a suspension of medical curiosity once a diagnosis has been made.” RP
And especially with autoimmune disease, because once you have one autoimmune disease the chances of developing another are really high. It’s really important to keep asking the question, ‘why?’. So for children, early functional testing is so crucial. For me, the three most important tests in a predictive sense would be:
1. Gut testing – Look at the gut microbiome, inflammatory markers, imbalances in mucosal immunity, changes in n-butyrate and secretory IgA
2. Blood chemistry – Look at anything that indicates changes in immune system regulation; changes in white blood cells outside of the norm, even if not in a diseased state
3. Predictive antibody testing – This testing is super critical in this population, because we know that auto-antibodies can be present for more than 10 years before the disease is really diagnosable. So if you can identify auto-antibodies early on, and the mechanism by which they are being triggered, and then deal with that, you have a real opportunity to head that entire process off at the pass.
“It’s like a snowball rolling down a hill. If we can identify the snowball at the top of the hill, and then stop it from rolling, we can then prevent that cascade of immunological and inflammatory events that lead to the destruction of tissue in autoimmune disease. And what a hopeful thing to be able to tell the parents of a child at risk of autoimmune disease…”
RB - Which specific tests do you use most often in this area?
RP – I use Cyrex Laboratories Array 5 (Multiple Autoimmune Reactivity Screen) & Doctor’s Data Stool Analysis. There are so many gut tests out there but this is the one I use in my practice most. I don’t think there is just one perfect test though, each test has significant benefits and limitations, but one of the things I think is really important about gut testing is the microbial library. A test cannot identify a microbe if it doesn’t have it in its catalogue, and it will report a negative in that instance, so it doesn’t say there’s a problem here but we don’t know what that is; it will say there’s no problem and I like Doctor’s Data because their microbial library is 1400 microbes…and counting, so they are constantly in the process of identifying new microbes, and the closest test to that only has 400, so it’s a really significant difference.
However, I also think that the way we do gut testing is on the precipice of some really big changes. I’m hoping that in 5 years’ time we aren’t using any of the tests that are currently available to us and that we have a completely different system for considering the gut and identifying what’s going on in there.
RB – The brilliant Christopher Bump (Viral Etiology & Autoimmunity) opened his presentation with a pertinent quote that beautifully echoes your point here. He said,
“My only conflict is a concern that what I present today will be obsolete tomorrow”
And this is such a critical thing to remember. Science isn’t black and white; it is constantly evolving and we have to stay open and curious as practitioners to the idea that what we think we know for certain, may not actually be the case…
RP – Absolutely, and for the past two years I’ve been saying the same thing about the gut – I think most of what we’ve been taught to be true about the gut is pretty wrong; it’s a wrong way of thinking about it, and I have been saying that for about 2 years. I think the interventions that we make do work, but I’m pretty sure that the reason we think they work is not the reason why they work. So watch this space, because I think our understanding about the gut is changing pretty rapidly, and I’ve been saying this for years, and now I feel that my early predictions are somewhat vindicated because the shift is coming …. watch this space!
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