Numerous environmental factors have been implicated in the development of autoimmune disease, including antibiotic use, birth by cesarean section, chemical exposure, poor diet, and sleep deprivation, among others (1, 2, 3, 4, 5). While it is widely believed that disease onset requires an environmental trigger, most autoimmune conditions have a genetic component as well (6).
Genetic information can be a powerful tool in aiding both diagnosis and treatment. One particular group of genes that has been strongly associated with various autoimmune diseases is HLA-B27. In this article, I’ll discuss HLA-B27, the role of a gut microbe called Klebsiella, and why a low-starch diet may be effective for those who have an HLA-B27-associated autoimmune disease.
What’s This about HLA?
“Antigen” in this case refers to cell-surface proteins. Putting it together, HLA is essentially a group of genes that determine which proteins are present on the surface of your immune cells.
Humans have a total of 23 pairs of chromosomes, with one of each pair coming from each parent. You therefore inherit one set of HLA genes from your mother and one from your father, on the maternal and paternal versions of chromosome 6. HLA is a highly polymorphic gene, meaning there are many different possible gene set variants, or “haplotypes,” that you can have.
The astounding number of haplotypes for HLA likely evolved to allow for the fine-tuning of the human adaptive immune system, but certain haplotypes can also predispose an individual to a particular disease of the immune system. You may have read my previous article in which I mentioned the role of HLA haplotypes in susceptibility to mold illness. HLA-DQ haplotypes have also been associated with celiac disease (7), while HLA-DRB1 has been associated with rheumatoid arthritis (8). For the remainder of this article, I’ll focus on HLA-B27 and its connection to autoimmune disease.
The genetic link between autoimmune disease and dietary starch.
HLA-B27 Is Associated with Various Autoimmune Diseases
The prevalence of HLA-B27 varies between ethnic groups and populations worldwide but is generally not a very common haplotype. Only 8 percent of Caucasians, 4 percent of North Africans, 2 to 9 percent of Chinese, and 0.1 to 0.5 percent of Japanese people possess HLA-B27 (9).
The most closely associated autoimmune disease with HLA-B27 is ankylosing spondylitis (AS), an inflammatory disease in which some of the vertebrae of the spine fuse together, inhibiting mobility. An estimated 88 percent of people with AS are HLA-B27 positive, yet only a fraction of HLA-B27-positive people will develop AS (10). Other autoimmune diseases that are associated with an HLA-B27 haplotype include Crohn’s disease, ulcerative colitis, psoriasis, reactive arthritis, and uveitis (11).
Making things a bit more complicated, HLA-B27 is itself polymorphic, with more than 100 different subtypes (12, 13). These are distinguished by a two-digit number added to the “parent” haplotype. Many of the most common subtypes of HLA-B27 (such as B2704 and B2705) are associated with increased risk of AS, while other subtypes (like HLA B2706 and B2709) actually appear to be protective against the disease (14, 15). This is likely due to the structure of the protein encoded by the HLA gene, as we’ll explore more in the next section.
The Klebsiella Connection
As early as 1980, AS patients were identified as having elevated levels of serum IgA, suggesting the abnormal movement of microbes from the gut into the bloodstream (16). More recently, microbiome analyses identified greater abundance of a gram-negative bacterium called Klebsiella in stool samples of patients with AS (17). Fitting with their hypothesis of bacterial influx into the bloodstream, researchers found that these patients also had elevated levels of anti-Klebsiella antibodies in the blood (18).
In other words, the immune system produces antibodies against Klebsiella in an effort to remove it from the bloodstream, but these antibodies can also “accidentally” bind to HLA-B27. This idea of antibodies binding to “self” is characteristic of autoimmunity.
Although Klebsiella is one of the most widely studied microorganisms in relation to HLA-B27 and autoimmune disease, the concept of cross-reactivity applies to a number of different microbial (and dietary) antigens. For example, Proteus bacteria have been suggested to be involved in the development of rheumatoid arthritis via the same molecular mimicry mechanism as Klebsiella (21). As we’ll see next, knowledge of these mechanisms and the bacteria involved can really help shape our approach to treatment.
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Why a Low-Starch Diet Might Help
The composition of the gut microbiota is constantly shaped by the influx of dietary substrates (22), including proteins, fats, and carbohydrates. Within carbohydrates, substrates can be further categorized as simple sugars and polysaccharides like starch or cellulose.
Biochemical studies of Klebsiella have shown that this bacterium does not grow on cellulose derived from plants but can grow readily on more simple sugars (23). Most simple sugars like glucose are absorbed in the proximal small intestine and therefore do not travel as far as the large intestine, where the majority of microbes are located. Simple sugars from the diet are therefore unavailable to Klebsiella.
Starch, however, is not as easily digested or absorbed, and some of it remains intact when foodstuffs finally reach the colon. Klebsiella have been shown to manufacture pullulanase, a starch-debranching enzyme, that enables them to break down starch into simple sugars for energy and growth (24).
Several studies have applied this information in humans. One randomized control trial split people into two groups: a high-carbohydrate, low-protein diet or a low-carbohydrate, high-protein diet. They then compared the abundance of Klebsiella in fecal samples. The average number of Klebsiella was 30,000/gram in the high-carb group compared to 700/gram in the low-carb group (25). Another study found that a low-starch diet reduced total serum IgA in AS patients (26). The majority of these patients also reported a decline in symptom severity and, in some cases, complete remission.
Take Steps toward Remission
Now that you better understand the science behind HLA-B27-associated autoimmune disease, here are three things you can do to take action.
Find Out Your Haplotype
Currently, there is no readily available, user-friendly means of determining HLA haplotype from full genomic sequencing data (from companies like 23andme). While there are a few HLA-related SNPs that can be identified in the raw genetic data, at best these are only correlated with HLA haplotype and do not provide information about subtype. The best and most accurate way to determine your haplotype is to request a blood test from your healthcare practitioner that uses a more targeted DNA sequencing approach to identify which alleles you carry (27).
Experiment with Your Starch/Carb Intake
Even if you don’t have access to genetic testing, or if you’re HLA-B27 negative, you can still do a self-experiment to see how you personally tolerate starch. I am a big proponent of n=1 experimentation and finding the diet that is right for you. Eileen Laird of Phoenix Helix has written an excellent post in which she shares the results of her own and several other Paleo autoimmune bloggers’ starch experiments. Many found that they can tolerate some forms of starch but not others. This is really valuable, since we know that a diet devoid of fermentable fiber like starch can be detrimental to the long-term health of the gut microbiota (28).
Heal Your Gut
At the risk of sounding like a broken record, healing the gut is absolutely critical to achieving and maintaining optimal health. A leaky gut allows bacteria and dietary proteins into the bloodstream, which provokes an immune response. Regardless of your HLA haplotype, strengthening the integrity of the intestinal barrier is an important step towards achieving remission. Supporting a diverse, healthy microbiota can also help to keep Klebsiella and other potentially problematic microbes at bay.
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Low Starch/ NO Grains works better for me too. I finally gave up even gluten-free grains, like rice, by my own choice, even though naturopaths still recommended gluten-free grains—but even rice gave me joint pain, lingering fatigue, more brain fog, bloated belly & sluggish digestion. My chiropractor couldn’t figure out why my muscles were so TIGHT and why his adjustments weren’t holding, until I gave up those grains & all starches. Thx for sharing this. Now if I could only fix the chronic fatigue & adrenals.
Low starch/carb does work for me. If I eat them, I literally can feel my feet start to swell as I’m chewing. I would also encourage people to consider that they may have a solanine issue as well which means no peppers or tomatoes. Any nightshade is out which makes the diet even more restrictive and if you’re picky like me..sigh, it’s really hard, but I do feel so much better cutting out the starches. I also have Uveitis as well, so I try to keep my inflammation and stress down. I am HLA-B27 +. I start feeling the difference in a matter of days when I cut out the starch. I haven’t had any back pain for at least 6 years now, but that was due to dealing with some emotion issues. When I let that go, the back pain went with it and I was left to deal with the Uveitis and Gerd. Before I discovered the carb issues, I had gotten fluid in my lungs and heart, but all my test were good for my heart. It’s been a struggle since I was 18 and I’m 52 this year. I just wish I knew about the carbs when I was younger. I think I could have avoided some of the issues if I had.
Also forgot to mention I have chronic sinusitis as well.
Wow, Nikki…. I can relate to you including the sinusitis. I’m now 58 and only just catching on that it’s not just Gluten but the starches from baked goods. Apart from the classic starchy potato what else do you suggest I eliminate?
Hello and thank you for sharing, Im too Hla-B27 positive. My Rumetologist suggested to follow a gluten-free diet. I just find it so hard to give up the carbs and starches, its like they fuel my body on one hand and hurts it on the other. Ill keep trying.:)
I’m not sure how gluten figures into. I think you can still eat starches like potatoes and beans on Gluten, just not wheat starch. I know potatoes are a huge cause of inflammation for me. Really pay attention to your body and how it reacts to different foods. I feel that is the key. We’re all different, so it would make sense that there is not just one diet solution. Yes, it’s hard for me to give up some starches like potatoes. Others, like bread and rice don’t bother me. I miss popcorn lol. Emotionally, it’s hard at first, but then I know I feel so much better without them. The first week is the worse and then it gets easier. It’s kind of upsetting because your first response is to feel deprived or like you’re being forced to give up things you like, but really we’re poisoning our bodies with them. I’m ridiculously picky, that mentally it’s rough, but I just started back up again. Sigh.
You have to keep repeating to yourself that you are not giving up foods….you are giving up pain and disability….you are worth the effort! What you are getting back is more vitality, better health, the ability to do things that you sometimes cannot do because you are in to much pain or too exhausted from the inflammation. And even the things you push yourself to do now, while in pain, you will enjoy with so much more quality of life once you remain in remission. It’s all worth it! But you cannot halfway do it and expect to see results. Especially in the beginning, you need to avoid completely 100% all starches to let your body heal. Just cutting out gluten is not nearly enough. You have to cut out all starches. But you can still have carbs. All vegetables are carbs. All fruits are carbs. You can even have green tea with honey in it. Or make cookies out of almond flour with honey for a sweetener. Once you get over the initial starch withdrawals, it gets so much easier and becomes just a natural way of life. I’ve been doing it for 6 years now. I rarely think about the things I cannot eat because there are so so many things I can eat that I am focused on. You mentioned that your body needs carbs for fuel, but carbs are not an efficient source of fuel. Once you cut them out, your body will start using fat as it’s prefered fuel source. This is a much better and efficient source of fuel, and it is what we were meant to use, not all the processed carbs we use today. So you will need to increase your good fats… Avocados will become your friend, as well as coconut and nuts like almonds and walnuts (most other nuts are too starchy), and good quality meats and pasture raised or cree range eggs. How long it takes for your body to adjust and convert to using fats for fuel is different for everyone. It took me only 2 or 3 weeks, but I have heard for others it took 1 month or more. Once it happens, you will no longer feel hungry. Your body will stop asking for starches. You do not want to cheat and eat start eating starches now and then because it will only confuse your body, are starches my fuel source now? Maybe I should not switch and start using fat as a fuel source? My body now burns fat as fuel very efficiently. You will get there. Make grocery lists ahead of time before stepping in the store and then head straight to those items only on your list. You are on a mission. Don’t even look at the other stuff. If your family is supportive to also trying the new diet, then even better! Clean out your kitchen and throw away all the starchy stuff. That way there will be nothing there for you to cheat on and to tempt you. Replace it all with snacks and foods that are not starchy.
Thanks for taking the time to give us a pep talk. I truly wish I wasn’t so picky. I will eat almonds and walnuts. I’m trying to make myself eat veggies (I hate most of them and get tired of eating the same things over and over that I barely can tolerate them). I truly wish I liked avocados and coconut, but I don’t. I’m pretty much down to eggs, meat (chicken, steak sometimes Turkey- I can’t have ground beef because it’s more acidic or tomatoes or peppers because they make me swell), cheese, fats (Walnuts and almonds), fish a few times a week and that’s it. And yes, I agree, after a week, I really feel better and already feel the change it’s just mental if I want carbs cause I really don’t want them in fact, I barely have an appetite at all and kind of have to force myself to eat. I tend to leave out fruit because I’m trying to lose weight and it stalls me. My kitchen is already cleaned out. For me, it’s just about sticking to it and not faltering. I’ve been on and off for two years. If I fail, it’s because I truly just get sick of eating the same things. I’m not sure how to change that because of the pickiness and the additional restrictions I have. I just try to suck it up. I’m a work in progress, but it’s a miracle that I have no back pain. I will just have to try to think of ways to be more creative food wise so I can make this a life style change.
Thanks Amy, I need to take a leaf from your book.
Fyi, Potatoes are a *Nightshade* plant, which can make people more inflamed, cause lingering fatigue AND joint pain. I cannot eat potatoes or sweet potatoes. Both are also high in *Oxalates*, which cause convert to painful crystals in the body. With RA I would be very careful & log your symptoms after you eat potatoes for several days after eating them. Delayed symptoms can happen up to a week later. Look at the “Raw Vegan” or “AutoImmune-Paleo” diet.
It seems there is a little bit of mixing up of terms, and meanings going on here.
Three main parts of food: protein, fat, carbohydrate.
Carbohydrate includes: starch (complex chains of simpler sugars); and simple sugars (glucose, lactose, sucrose, fructose and others).
The Post here is about starch only, not carbs in general. It is the complex carbohydrates that get far enough into the system to feed the Klebsiella, that appear to contribute to the disease.
The simple sugars don’t appear to be problematic here. There are lots of other potential problems with simple sugars, or large amounts of them.
Some people, for various purposes, find a low or zero carb diet useful or necessary. Their energy needs have to come from fats mainly and the body switches how it derives energy.
My purpose here is to advocate the judicious use of glucose to support your energy requirements. (That is if you are not choosing a ketogenic diet).
May I refer you to my comment of August 29, 2016.
My son was blooming, on 65 teaspoons of glucose per day.
I’m not advocating that. But 1 wouldn’t hurt you. 2 wouldn’t hurt you. Probably 10 wouldn’t be too bad, it’s what people get in some soft drinks. Perhaps 1 teaspoon per hour for every waking hour. Perhaps 2.
It’s up to you.
It can give you part of what you need.
It can make you feel better.
It can stop you feeling grumpy.
I ran a marathon once. Basically you can’t do it unless you pour in glucose and salt along the way, else your body runs out.
All the best.
Whole Raw Fresh Fruit & Raw Honey is a better option for simple sugars, instead of….. sodas, refined white sugar, High fructose corn syrup, sugar syrup, gatorade etc…
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So I was recently diagnosed with Hashimotos and also tested positive for HLA b27… had xrays done and they said no sign of AS. I do have terrible joint pain , especially neck and tailbone, so now I am confused on what that means for me… in 95% it’s AS what is it in the other 5% ??? I am 35yo female. I get massages and adjustments weekly due to pain.
Hello! I’ve had AS for years but did not find out about it until last year. Got diagnosed with Hashi’s late last year. Low starch diet combined with AIP for about 6 months so far….And the pain and flare-ups are better. So give the low starch approach a go! The one dilemma I have (and you will too possibly) is – for Hashi’s, we need carbs/ starch, for AS, they hurt us….Where do we go from here :)? My Hashimoto’s has gotten worse since last year, AS better.
I just had to reply to your comment after I read it because I feel for you! I had severe hip, neck and spinal pain for years. I’m in my 50’s now and was 19 when I had these symptoms. I was checked for things, had an MRI, back X-rays of my back and they could find nothing. At that time they considered AS a “man’s disease”, so no doctor thought to test me for it. Long story but I was finally diagnosed with AS. It will not show up in X-rays or MRI often and often only when you’ve had it for years. Don’t give up, Find a Rheumatologist with knowledge of this disease. Also check with family member to see if they either have it or have symptoms of it as it is very genetic. It’s also very painful though it can go in and out of remission. It you have the symptoms and the HLA-B27 gene, IMO you have a strong likely hood of having it. It’s also auto-immune so if you have other auto-immune diseases, that increases your chances. I’m mentioning all of that because the more risk factors you have for it, the more likely a doctor is to consider it. I hope you get a correct diagnosis, esp. if you are living in a lot of pain because today they have medication that can treat it. When I was diagnosed so many years ago, there was nothing and I was in horrible pain with no answers and I don’t want anyone else to suffer like that. Mine has gotten better as I’ve gotten older, only that I have about 10 AI diseases now, most are worse. I hope a doctor will listen to you and test you for it and diagnosed you correctly so you can get treatment if you need it.
You have to have AS for more than 10 years before the joint damage is sufficient to show up on a mere x ray. It is very, very common for x rays to not show AS. It did not show up in my x-rays either. But then the doctor ordered an MRI which is much more detailed, and that showed the beginnings of the disease. If your doctor did not know that you needed to order an MRI instead of relying solely on a silly x-ray, then you might need a new doctor. This is a big problem with Ankylosing Spondylitis. There’s a huge delay in diagnosis. If you have all the pain and symptoms of AS, and the gene to go along with it, then just proceed assuming that you have it and get started on the diet protocol. Observe if you have relief. But in order to be a true fair test, you must stick strictly to the diet in the beginning and give it a good 3 months trial to see if you feel better.