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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Our son (early 40’s) has ulcerative colitis, and so far is managing to keep full-blown flare-ups at bay through diet and supplements without prescription drugs. He had to go naturopathic because he reacted allergically to all the drugs normally used to control the condition, and refused to try remecade since it is a genetically manipulated IV administered med containing both human and trace mouse DNA. So, his diet is non-GMO, dairy-free, soy-free, caffeine-free, alcohol-free, canola-free, gluten-free, processed sugar-free, and at the moment, red meat-free, and no raw veggies. Even a minute amount of these leads to inflammation and colon pain.
In being gluten-free, he avoids most grains, but tolerates gluten-free oats, grain alternatives, and paleo baked items. Interestingly, he also must avoid all products made with bread yeast, which in doing some research makes sense because baker’s yeast is cultured commercially in either malts or molasses, both of which contain traces of gluten as well as have a relatively high glucose/fructose content. Because of dietary restrictions, he does struggle with some nutrient deficiencies if any inflammation is occasionally present which restricts absorption, so his iron levels can be low along with resultant fatigue and low immunity to fight viral infections
This article therefore does lend some scientific explanation as to why starch carbs (particularly from gluten grains) and sugars may be factors in triggering the autoimmune disease sequence at the genetic cellular level. He was asked by his gastroenterologist to participate in a scientific study soon to be conducted at the University of Alberta to determine whether inulin and polyglucosaccharide pre-biotics have a positive anti-inflammatory effect without having to surpress the immune system. He refused on the grounds that to participate in the double-blind study he would have to alter his current dietary and supplemental regime, and he did not want to go that route simply because so far what he is doing seems to be working, and he already knows from past experience submitting to the required sigmoid and colonoscopies during the study would set him back with little recourse to manage any resultant adverse flare-up since he has to be drug free! But otherwise, he really is interested in the resultant findings of this study, especially since he already is incorporating pre-biotics and pro-biotics into his current treatment regime, and is fairly low carb.
My father had ankylosing spondylitis. I have celiac and have found that gluten free grains cause many of the same symptoms as gluten (brain fog, achey joints, gastric issues and a toxic feeling that lasts several days). I don’t have this issue with starchy vegetables. This could explain why. Thanks.
3 weeks on no starch diet. I would say that my pain level went from 7 to 5,5 but I lost weight, what is not very good for me but I continue.
Check out The Plant Paradox! It may reduce your pain even more.
I already posted how the Low Starch Diet has tremendously made a difference in managing my symptoms of AS for the last 5 years, and I am HLAB27 positive. I am just curious….is there anyone here who is NOT HLAB27 positive, yet they have still found the Low Starch approach helps them?
I have AS and follow a low starch diet to control my symptoms. Have not been tested for HLA-B27. When my symptoms developed I knew that dietary changes would make difference – we recovered both our children from severeTourettes and OCD through diet and supplements – so I started searching and found the info on low starch for AS. Boom! With persistence and tweaking for individual needs, I went from near non-functioning to living my life. From 7-9 on the pain scale to 1-3. N=1, it works for me.
Deborah,
What diet and supplements did you give your children to help with their OCD?
Hi; I am so grateful for this info! I have palmpustular psoriatic arthritis/spondolitus, negative for HLA B27, but, have significant damage in SI joints and thorasic 6-12 fusing. I am 60 and have had this since mid 40’s but not diagnosed till 2 yrs. ago. I did a round of prednisone/methotrexate for 3 months, quit, and went on starch-free. cut severity of flares by 1/3 and am not bedridden. Flares last 2 to 3 weeks and cycle every 35 days approx. Recently I saw an MD, bio-med researcher dermatologist who told me I need to be on Stelara. Researching this I am unsure as to what to do. I had IBS most of my life until going starch free. I am following all leaky gut protocol/supplements, all of it! Even donating blood as I have excess iron in my blood. I did testing for heavy metals etc. I have better gut/digestion etc. now but still flare and the pain is debilitating. Should I continue on my path or risk going on the biologics. I don’t even take NSAIDS anymore for 2 yrs. now. How long can it take and can I send this into remission? Hard ??’s to answer I know! I would appreciate anyfeedback. Thanks!
I would be suspicious that you are being sold expensive drugs to treat symptoms… when diet and supplements may help you more. Look for a functional doctor, even if you have to travel and pay out of pocket, they will look for root cause.
Hi there, my son takes Humira and gets stellar results. He’s only 21. Your Rhumo doc can tell you all about it. Get on humira plan thru their company and the meds are only $5.00.
I would also recommend seeing a Functional Med Doctor. You may need to detox and your gut may take longer to heal, depending on the severity of damage. That’s awesome that the IBS symptoms are gone. Focusing on healing the gut is so important. I have Crohns AND Ankylosing Spondylitis. My gut symptoms improved dramatically by cutting out starches, dairy, and refined sugars. I found hidden sources of starch in my supplements and meds. Once I cut those out, my symptoms improved even more. So important to test EVERYTHING with iodine that goes into your mouth. I also took Ancient Nutrition Bone Broth Protein Powder and made smoothies with coconut milk and frozen blueberries. I used Green Tea Extract drops (half a dropper mixed in a glass of water) every day and I took Ginger Root capsules for inflammation and probiotics (I had to experiment to find one that helped) and fish oil. Over time, as my gut healed, my AS symptoms got better and better with fewer relapses in between. A Functional Med Dr will help you sort all this out. I would try all that FIRST before resorting to the meds. Conventional Docs wanted to put me on biologics years ago and just thought I was insane for managing my symptoms with diet and supplements. But when it came down to it, they couldn’t argue the results. I may still have a flare now and then, due to hormones, stress or the weather, but maybe only a couple times a year. I asked that Doc if I were on the Biologics, would I be free from all flares, and he said No, most patients still have flare ups, but the drug is considered to be working if the flares are reduced to only 3 or 4 per year. I looked at him and said that I have less flare ups than that now with my own approach, so why would I want to mess that up and make myself worse? He had no answer.
Thank you for this article! I was diagnosed with AS back in 2012 and am HLA-B27 positive. I have struggled with severe SI joint pain since 2010 (starting when I got pregnant with my first child) – typically with a constant low grade pain, but on three occasions with a flare so severe that I couldn’t walk for almost a month because it felt like my hip would collapse if I put any weight on it (this happened at 6 weeks postpartum with each of my kids, and then randomly one year ago). I discovered the low starch diet a year ago and immediately stopped eating all grains/potatoes/etc. A month later I stopped eating dairy and refined sugar. This brought my pain down significantly but I still had random flares here or there, especially as I tried to add back in certain starchy vegetables. I took the LEAP MRT (a blood test that tests for delayed sensitivities to 150 foods) and discovered that I was severely sensitive to two foods I was eating regularly (beef and pork), and moderately sensitive to several other foods (including many of the veggies I noted caused me problems earlier). I stopped eating all of those foods in December 2015 and have been pain free since then (unless I cheat, which happens occasionally).
Around the same time I started eating fermented foods with the hope of diversifying my gut bacteria and healing my gut (kimchee, kombucha, water kefir, milk kefir, natto). I think of it as having 20 people in a room (i.e. a diverse microbiome) – if one of them starts getting unruly, the other 19 have a very good chance of stopping the unruliness. If there are only 2 people in the room, there is very little chance of stopping the unruliness.
I agree with Chris that a diet that is low starch or too low carb is ultimately bad for your gut bacteria (good or bad) – and I am always trying to diversify my diet – so about three months ago I decided to try a few french fries at dinner. I found that I was able to eat them without any issue, and have since added in breads made from sourdough starter – I think that the fermentation process in sourdough helps my body break down the bread quickly. I should say that I started with potatoes because the LEAP MRT test I took showed I didn’t have a sensitivity to them. I have not had the same luck with rice, sadly. Either way, I stick mainly to a low starch diet and eat some potato and sourdough here and there. The diet has really been a life saver and I *almost* feel normal again (minus some thoracic back pain I can’t seem to get rid of). Thanks for posting such a great article about the connection between HLA-B27 and starch!
I am in my 50’s and have had issues throughout my life mostly with various sleep issues and fatigue. Severe PMS (later told PCOS), early environmental allergies with high antibiotic usage and possible mercury exposures etc.
Told as a teen I had mold allergies, dust mite, dander causing my chronic rhinitis. Also, later on some severe antibiotic and pain medication allergies.
About 10 years ago started getting more then normal aches and pains. Prior to these I had a hysterectomy, and then told I had insulin resistance a couple of years following that.
High family history of cancers and autoimmune disease, but so far just keep getting told I have non definitive, elevated inflammatory markers and test negative for….
I have been struggling trying to figure out how to get passed the fatigue and think how to fix the pain, but keep getting lost.
I think I am on the right track with some things though eg. (Looking back, high stress from various life situations prior to unplanned move to an area with high humidity, home that had leaks months before we bought it and several medications that I now believe contributed). I actually had just requested an HLA-B27 test 2 months ago (told it was also negative) and recently started questioning mold with heavy rains this year, while struggling with what to eat and steadily falling farther behind on life and feeling overwhelmed about how much I am missing out on.
Anyway, I have questioned getting so much worse when I had cut out more meats and added in more beans and grains years ago after being told to do that because of family colon cancers and (just prior to insulin resistance showing it’s head) and despite being told no that could not have been the issue I have been gravitating back to a more paleo diet. However, just had doctor tell me the other day I need to add more grains, veggies and fiber to my diet (without even asking me what I was eating).
I am so lost… It is so hard to think my way out of this.
Is there not something I can easily just print out and follow along to start to feel better?
Hi Beth – my heart goes out to you with all your health issues. I too am in my fifties and have had a lifetime of health problems. All my tests came back negative and I’ve been made to feel that I was making it all up. After no resolution from two rheumatologists (and many other doctors along the way) I’ve been muddling along on my own.This year my pain reached crisis point and i decided to try one more rheumatologist – a really expensive one with a good reputation. He has finally diagnosed me with spondyloarthropathy, main components of ankylosing spondylitis, plus Sjögrens and fibromyalgia. I gave up his medication after two months of horrible side effects and switched to the no starch diet. It has been fantastic, though not yet perfect. I’m finding that there are other foods I need to watch out for like nuts and seeds – they also give me pain. I’m dairy free except for butter. How about going strictly starch and dairy free for a few days to see if it helps? If it does, you could slowly reintroduce other foods to see what’s what. You might find more help on the Kickas website. Good luck!
Thank you for this article. I went to my doctor with “arthritic-like” symptoms, stiff, noisy joints, extremely painful back, fatigue. He tested me for Klebsiella and HLA-B27 (unsure of the subtype). I was positive for both.
He suggested a no starch, no sugar diet (essentially Paleo with a few modifications for the no starch & no sugar). I can attest that almost immediately my pain went away and I had so much energy back. I can also add that for me this isn’t a “sort of Paleo diet” or “80% paleo”. It’s all or nothing for me personally. If I eat any starch or sugar (including fruit) the pain comes back almost immediately.
I’ve been on this diet for over 2 years, the healing process is slow but so worth it. I would also add my mother that has has “arthritis” for most of her life has gone on the diet as well and has had tremendous pain relief and success.
Best to all.
Wow I’m impressed by your doctor. Where are you located?
Yes I’m so fortunate to have Dr Leo Galland in New York City as our family doctor.
We have this conversation often in our Spondylitis group. Based on Dr. Ebringer and the London AS Diet. Many follow it with success, some being a little more Paleo & adding intermittent fasting.
I will ask my dr to test. I do have high igA, at the top end of normal range. Can celiac disease cause that? ( I have it ) and / or can candida cause high igA too?
Thank you Chris, again, for all the research you’re doing and informing us.
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Although I don’t have a “starch problem” having reduced “simple starches” does seem to add to better health for me!
I think what you’re discussing is just the tip of the iceberg…and soon many more “genetic connection’ will be linked to other diseases.
I had been diagnosed of HLA-B27 positive about 6 years ago after undergoing a severe episode of Iritis and major back and lower hip pain. Ever since, I have had done a lot of reasearch on my own and through a support group called Kickass.org, I started experimenting the low start diet. I highly recommend a book called “IBS Low Starch Diet” by Carol Sinclair. It has a lot of interesting and useful information in it. Although I would still get flare ups in my eye every year or two, my other symptoms in the joints have reduced tremendously ever since I cut out my starch and processed sugar. My next goal is to have put my Iritis in remission as well.
I am HLA-B27 positive and went gluten free and now low starch. I can tell a big difference in joint pain. Wanted to let you know, I discovered my iritis is triggered by hair dye. I am able to use Henna, but everything else seems to trigger a response – even the hypoallergenic dyes result in a bout of iritis approximately 2 – 4 weeks after use.
Hi Sharon, thank you for youre insight, I have gone Gluten-free for the past couple of weeks and wheat free, my low back pain has subsided a bit, someone at work told me to take Magnesium and thats also helping for over all body aches. I am a young 54 and try to stay active. finding it hard to choose some meals like breakfast as I loved my toast and peanut butter and now I cant have that, but I guess its a small comprimise if its going to make me feel better!! Thanks again.
Thanks for the article helping me understand what HLA B27 typing actually means.
Erythema nodusum is another auto-immune disease associated with HLA B27 typing. I understand some families with A.S. will sometimes have other members with Crohn’s Disease.
Thanks for doing all the research for us, Chris, and explaining it in a comprehensible fashion.
Could granuloma annulare be a HLA-B27-associated autoimmune disease?
I would like to also know if granuloma annulare is a connection. I am also fructose intolerant.
hi chris I was Dx with AS 33yrs ago and I am HLAB27 positive. the lower starch diet and following the AIP and now going Paleo has helped me significantly. Thanks for a informative post.
Keep up the great work as I’m a big fan and follower.
Hi Chris,
I have AI condition since child.
My history: birth by cesarean, i don’t have mother’s milk, psoriasis, many alergic crisis, and high doses of cortisone
My gut “was broken” when I have 16 years (ten years ago), and for many years I used laxative pills diary. Sad.
Today i’m diagnosed with celiac disease also
Many doctors said (during all my life): it’s emotional, you need therapy
So, I had therapy and pay lots of money for nothing
I started Paleo in 2013, when (like you) I had a general colapse in my health
Since when I cut off starch of my life. And slow down all carbs.
I tried resistent starch some times, but it’s horrible for me also.
Many fibres are horrible X 100.
I’m using cycles of Elixa (www.elixa-probiotic.com/) like a probiotics since last november, and is very well.
Today I’m Keto, and supplement with oil fisl, d3, multivitamin, gaba – and sometimes with 1,5 mg of ldn.
I have acupuncture and autohemotherapy (10ml) once time at week
I’m brazilian and Scientist of Human Ecology. My job give me knowledge and freedom.
I learned so much with you in the last years
Thanks for all
Hugs
I forgot to add that I do have an autoimmune disease namely ocular myasthenia gravis
Actually, I have been on a very restricted minimal carbohydrate diet for a number of years, still with chronic pain from osteoarthritis. I have also had constipation issues. I have recently begun to add limited carbohydrates to my diet in the hopes that this will help with my constipation issues. Thanks to this article, I will be very cognizant to observe any changes in my osteoarthritis symptoms. Thank you
Try taking a Probiotics capsule daily
I say give us proof. Tired of all the here say.
BL- In this short article Chris cited 28 studies to support the hypothesis presented and suggested using the principle of n=1 (self-experimintation) to determine effectiveness on an individual basis. What further “proof” is needed to give the ideas presented merit in your mind?
Like you, I want proof too!
Luckily for both of us, Chris includes references to the scientific literature for each of his claims. See those numbers in the brackets eg “(28”) at the end of each paragraph? Click on those and then read the articles.
The proof is in trying it yourself, won’t hurt you, won’t cost you much, simple but takes some effort, its going to be positive benefit or not.
I am proof. A low-starch diet reduced my AS symptoms about 80-90% (I started the diet in January 2012). It’s not even that hard to try out and see, as the symptoms will resolve quickly. The downside (obviously) is that avoiding starch is a sizable dietary adjustment. For me, I learned low-carb wasn’t very good for me either and I was inadvertently starving myself, so now I actually consume a fair of amount of simple sugars (honey, maple syrup, sucanat, fruits that are ripe, even some natural soda sometimes, like Reed’s Ginger Beer, coconut water).
I also discovered lactose sets off some mild symptoms. So, I tend to avoid that too.
I’ve been on the no/low starch diet for 3.5 years and I can say that I’ve seen an immense difference. I am HLA B27+ (haven’t checked deeper than that) with numerous AI issues (Axial spondylitis, psoriatic arthritis, PBC, colitis, psoriasis…) It took 3 months of strict no starch to see results, but that first morning of waking up without pain cinched the deal. If anecdotal evidence means anything (and I believe it does), I encourage you to check out kickas.com or The Low/No Starch Diet for Ankylosing Spondilitis page on Facebook. There you will find a community of people who have conducted/continue to conduct this experiment on themselves, and who tweak the approach on a personal and daily basis.
Yes, I have a autoimmune disease called Mixed Connective Disease.
The effects of carbs and sugar sounds like a case of Candida, if you ask me. Been dealing with since many antibiotic back in 2005. They are now saying autoimmune disease is caused by an infection. There you go, good old Western Medicine!
I also, like thousands others, am living proof. I have AS and Crohns. I started in 2012 with a 3 day fast, and then the low starch diet. I went from a pain level of 10 down to a 5 within about 4 days. So I was encouraged to stick with the diet. After 2 weeks my pain was down to a two and I have maintained this success since then. I was taking no other medications at the time so nothing else could have had this affect but the diet. If I deviate from the diet by eating even just one spoonful of starch, my AS pain shoots up to a 10 again within 2 hours. What other proof do I need. That’s more powerful to me than a piece of paper with writing on it. However, there is a substantial amount of written scientific proof as well. Do yourself a favor and experiment with the diet. It can do no harm. But to be a fair test, you must follow it strictly and not cheat. I suggest starting off with a mini fast first, to clear your body. For more information, keep your eyes open for a new website that will be coming Online in a couple months: http://www.AnkylosingSpondylitisCenter.org.