The best place to start is the INCREDIBLE website kickas.org. Go there. Register and support them! Here is a link to the Technical Papers section of kickas.org
Here is a page directly from kickas.org. You should go there to see the original and also to register on their site. Many thanks to everyone over at kickas.or, most especially Dr. Ebringer.
Much of the recent useful research into AS has been conducted at Kings College, London, by Doctor Alan Ebringer and his colleagues, together with his work at Middlesex Hospital, London. Their findings have been summarized in this primer for use by asweb.com, created and supported by Tony Browneller, as an outgrowth in support of the asweb, created and supported by Brian Harris.
During the previous several months, we have been introduced to Dr. Ebringer’s work by George McCaffery, who generously spent his time and resources on sending many of us first a series of technical papers concerning Ankylosing Spondylitis, authored by Dr. Ebringer et al, and then copies of Carol Sinclair’s book “The IBS Starch—Free Diet.” George had been on the London AS Diet, and under the care of Dr. Ebringer for the previous approximately ten years with excellent results, and better still recently on the Sinclair Diet System. Carol’s book is filled with good information and many recipes with specific dietary guidelines to eliminate starches altogether.
Klebsiella Pneumoniae, a bacterium normally residing in the digestive tract, causes Ankylosing Spondylitis in persons who are uniquely susceptible to this disease (1). Susceptibility is conferred upon an individual first via a genetic predisposition which can sometimes (but not always) be detected by the presence of the histocompatibility factor Human Leukocyte Antigen B27. Next, there is speculation of a secondary ‘triggering’ agent or event, possibly another bacterium or even viral exposure, which might cause persons of this genotype to develop the AS. Some of these studies conducted by Dr Ebringer also verify the certain connection between HLA DR4/DR1 genotypes in susceptibility to Rheumatoid Arthritis from a different antigen, another bowel flora called proteus mirabilis.
Beyond identification of K. pneumoniae as the causative agent behind AS, Dr. Ebringer has employed a diet low in starch, both experimentally and in clinical practice, to reduce the primary food source of this bacterium (5). This approach actually lowers this species’ population in the digestive system, and has had marked effective results in the treatment of AS, and will likely become the preferential treatment in the near future.
IgA: Antibody, immunoglobulin A specific to klebsiella pneumoniae.
IgG: Antibody, immunoglobulin M specific to proteus mirabilis.
UC: Ulcerative Colitis
CD: Crohn’s Disease
RA: Reactive Arthritis
AAU: Acute Anterior Uveitis
AS: Ankylosing Spondylitis
It is estimated that approximately 7% of the conglomerate human population has the characteristic marker antigen B27, but less than 20% of these will get AS. Of these, perhaps 35% will actually require diagnosis and treatment; most will be either sub-clinical (not ill enough to warrant medical attention), or have totally inconsequential or unnoticed levels of this condition. Some few people actually have AS, but not the B27 marker. It is likely that these persons are genetically quite similar to those possessing the B27 characteristic, and the disease mechanism (K. pneumoniae) is the same as those with B27. These cases are identified typically through X-rays using classical definitions of Ankylosing Spondylitis.
The definitive determination of the disease can usually be made by proper use of X-ray information, although, in very early stages, incipient fibrosis might not show up clearly. AS is a progression of fibrosis leading to calcification which begins in the lower spine, especially around the SI (sacroilliac) joint, and travels up the spinal process over a period of years. To some extent, hips, shoulders, knees, heels, and eyes are usually affected during the course of this chronic illness, and there are many other conditions which often accompany AS: Kidney stones, chronic Ulcerative Colitis, jaw involvement resembling TMJ, heart problems, bursitis-like shoulder involvement, knee problems, psoriasis, and, especially, the side effects from some of the medications employed to treat the basic condition. As many as 30% of AS victims will eventually develop Acute Anterior Uveitis, and often the AS diagnosis is made during treatment for AAU.
Persons suffering from Acute Anterior Uveitis, but are both AS and HLA B27 negative, have characteristically higher IgA levels than those with B27 and no AS (3), which might imply a greater sensitivity in persons with the B27 marker. Further, the presence of AAU in patients with AS might generally indicate an increased severity of the AS disease process (1), whether B27 positive or not. This seems to indicate that AAU (iritis) likewise, is caused by the antigen K. pneumoniae, as a separate disease from AS. Certainly, several other pathogens can trigger AAU, including STDs; these might actually create intestinal lesions which could lead to elevated levels of K. pneumoniae and concomitant increased IgA.
In conditions of RA, joints become inflamed, especially in the extremities. This kind of inflammation is quite similar to that experienced in all of the autoimmune conditions, and there are degenerative side effects from this kind of inflammation, also.
The similarities between RA and the three conditions of AS, UC, and CD, would indicate that although there are different factors involved in the production of RA, a very similar overt expression in autoimmune terms does exist; joints become inflamed and might deteriorate, bone calcium management is affected, movements are painful, and many other ailments can appear. There is a genetic predisposition in both situations, and both are due to antigen—antibody involvement, which has been identified in both cases: The antigen (germ) reservoir in RA is likely the kidney-bladder system for proteus mirabilis, which clinically affects mostly persons with the HLA DR4 marker. The antigen reservoir for AS, UC, and CD is likely focii within the intestines for klebsiella pneumoniae, which affects persons with the HLA B27 marker and similar genotypes, as well as other individuals which may have uniquely higher susceptibility to K. pneumoniae infection (4).
Individuals with AS, CD, and UC all exhibit elevated numbers for klebsiella specific IgA, but test normal for proteus mirabilis specific IgG. Conversely, those who suffer with RA test normal for IgA, but have elevated proteus specific IgG. All subjects have permeable intestinal membranes most likely due to NSAID usage (2). Further, it has been proven that many other expected enterobacteriaceae are either effectively excluded by the bowel mucosa, or do not elicit any similar immune response.
Even those species known to cause arthritic symptoms tested negative in subjects with these autoimmune diseases. Many species which should be present in conditions of permeable membrane are conspicuously absent: Borrelia burgdorferi, Campylobacter jejuni, Chlamydia trachomatis, Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium, Shigella sonnei, Staphylococcus aureus, Streptococcus pyogenes, Yersinia enterocolitica, and a yeast—Candida albicans (1).
Whenever the body is subjected to any substance, one of the first reactions which must take place is to determine whether it is friend or foe. Microbiologists call this the “self/non-self” recognition response. Foods often elicit allergic (non-self) reactions, but due to the manner, location, and speed with which foods are processed, any such reaction usually will go unnoticed.
The digestive system has the basic function of reducing foodstuff into simple components which can be absorbed for use as energy or cell building. From the moment anything enters the mouth, the alimentary tract begins extracting food values across a membrane called the mucosa. This mucosa is an important barrier to exclude materials not ready for absorption, while not allowing the wrong body fluids to leak into the tract.
Near the end of the digestive process, a symbiotic mechanism is in place to more completely utilize foods which are not easily processed earlier. This symbiosis is with varied bacteria which take up residence in this narrow ecological niche, and derive life from the chemical processes which they can initiate, and whose byproducts are further absorbed by the lower intestines. There are over one hundred (7) different varieties of ‘enterobacteriaceae’ which constitute the normal ‘intestinal flora.’ A sort of fermentation occurs, and continues to some extent, even after spent food has exited the body as fecal waste. Hearty bacterial colonies which live in all fecal matter have been the cause of many serious diseases when they accidentally enter any general water supply, such as during times of flood or general poor sanitation and improper waste management.
Intestinal bacteria can become problematic and cause conditions we are familiar with such as dysentery (Shigella dysenteriae), typhoid fever (Eberthellia typhi), and more recent outbreaks of disease generally identified by the offending species such as Escherichia coli and Salmonella enterica.
Certain kinds of reactions to viral and bacteriological agents will cause the body to be immunized to these specific agents; the immune system ‘learns’ to manufacture cells, called antibodies, which help destroy a specific invading substance. Upon repeated exposure, the body’s defenses are thereby more quickly summoned to inactivate and destroy the offending substance by more rapidly manufacturing these unique antibodies. Inoculations work in this way, to ‘train’ the immune system against exposure to more active strains of a specific organism.
In allergic reactions, the allergen (invading agent) does not directly cause the undesired reaction; but instead, it is the body’s own defense mechanism which over-reacts, causing an ‘autoimmune’ response. Simple allergies are usually due to an overproduction of histamines, which have systemic consequences and can be deleterious to the body beyond just being uncomfortable. The four autoimmune diseases operate in this way; the pathogen does not cause damage, rather the body’s own defenses become the problem.
Although they may attack (attach to-) offensive bacterial agents, the immunoglobulins might also mistake normal body tissues for the antigens against which they have been manufactured. This can happen when those structures used by the antibody to identify a target bacterium too closely resemble sites on body tissues. In AS genotypes, connective tissues are mistaken by the IgA antibodies for K. pneumoniae, and destruction of local structures will occur. This reaction has been termed “molecular mimicry,” and the mechanism has been supported by strong evidence, to the extent that the exact sequence in the identifying surface structure has been identified. The older, and commonly accepted “Receptor theory,” requires a series of complex events and conditions which many good studies have proven are very unlikely. Most probably, there is a similar mechanism in the autoimmune RA with IgG antibodies.
In a normal infectious process, antibodies are produced which cause the invading organism to be consumed by the body’s normal defenses. This cycle produces excess material which, when not removed fast enough, accounts for much of the swelling characteristic especially of these four autoimmue diseases. Many of the waste products occur within the lymphatic system, and the lymph nodes become overloaded.
The swollen lymph nodes create pressure and corresponding pain, and the proximity of active nodes to the lower spine causes this area to be affected first, in early cases of AS. The inflammation, due to ‘activation,’ or reaction between the cells, which contain HLA B27, and IgA, leads to a fibrosis condition which later becomes the familiar calcification called ankylosis (1). Chronic inflammation, in the case of AS, is due to a recalcitrant infection by the antigen K. pneumoniae, and evidence of this fact is found first by determining an increase in general antibodies, called erethrocytes, within the blood.
The primary test method by which to gauge the extent of infection is the Erethrocyte Sedimentation Rate. ESR is a measure of the speed with which cells are killed within the humoral (blood) fluids. The results of this assessment are given in millimeters per minute, and larger numbers indicate greater immune activity. Readings much over 15 indicate an abnormally high process, and it is not unusual for chronic sufferers to average 38 and even peak above 77.
The mechanism of AS begins with activation, which is caused by many IgA attaching to many receptor sites located on the HLA B27 surface. This promotes the complement cellular reactions leading to destruction of body tissue resulting in inflammation. Prolonged activation leads to fibrosis, a thickening of the synovial fluids, which, when present over extended periods, will lead to the characteristic calcification called ankylosis. This mechanism will not occur under low concentrations of IgA, where they do not have the numbers to initiate cellular necrosis.
NSAIDs relieve the swelling by dilating the capillaries to ease both the mechanical pressures as well as potentially block some of the neural responses which transmit pain signals. Steroids, notably cortisone and prednisone, have similar anti-inflammatory activities, but the many side effects make them very undesirable for long term employment Certain immunosuppressive agents, like methotrexate, interfere with the production of immunoglobulins and other vital elements of the immune system..
Although drug intervention is of considerable import in the diagnosis and treatment of the autoimmune conditions, it should be used only temporarily and sparingly, now that the genesis of these diseases is better understood. Drugs, in general, are recognized by the liver as poisons, resulting in extra systemic stress placed upon the body to remove them. There are side-effects and sometimes severe contraindications. For example, as many as 16,000 people in The United States annually die from the normal use of powerful NSAIDs, due to spontaneous bleeding ulcers.
Many studies were conducted by Dr Ebringer and his associates, first leading to the identification of K. pneumoniae—specific antibodies as the causative agency in the production of AS, and next excluding most other likely agents. The studies progressed over an extended period supporting prior results and adequately answering questions of HLA B27 linking in varied racial groups. Additionally, logical support for the molecular mimicry theory has advanced the understanding of mechanism in all cases of AS, UC, and CD, with certain implications in the genesis of RA. Most important is the potential for more effective treatment of AS and avoidance of the structural deformity which accompanies the progression of this disease. This has already been demonstrated using the “London AS Diet” over a considerable population of AS patients.
In victims of AS, it has been proven that there are elevated levels of IgA specific to the bacterium klebsiella pneumoniae (1). Further, the mechanism whereby IgA attacks the wrong cells of the body is generally understood and adequately explained using the ‘molecular mimicry model.’
Supporting molecular mimicry, it has been determined that tissue, especially collagen or connective tissues, manufactured by bodies of certain genotypes, has a similar appearance to the K. pneumoniae bacterium. The protein sequence covering K. pneumoniae is used by the immune system to identify it as an undesirable pathogen, and IgA attach to these markers on the bacteria to begin their elimination (1).
In general, many of the characteristics of AS have been summarized and compared to RA, by way of example, to formulate some causative agency, although many of these still remain as unanswered questions:
The male/female ratio for B27+ AS victims is 3/1, while in AS patients who are B27- male/female ratio is 1/1, and for RA it is 1/3 (1). 96% of AS patients are B27 positive, and 70% of RA patients are DR4 positive (1). Concordance between identical twins for AS is 40%, for RA it is 20% (1). B27-negative AS patients are seldom as severe as those with the marker, usually having later onset of symptoms.
In general, theories can be proposed concerning an increased incidence in males over females. Considering the fact that moderation of the immune system occurs during periods of pregnancy so that the fetus is not rejected, it may not be surprising that females have lower rates or delayed onset of AS, while this generalized fact opposes the observed higher incidence of RA in women.
Also, the incidence of CD and UC is very much higher in cases of B27 negative AS. The fact that these genotypes exhibit elevated IgA levels does implicate K. pneumoniae in the genesis or regeneration of the disease process.
That the IgA is markedly elevated in subjects with AS, CD, and UC, while many other agents have been tested for and not found, and especially antibodies specific to those most obvious anitgens such as Salmonella, E. Coli, Yresina, and even mould spores, indicates, beyond reasonable doubt that K. pneumoniae is the provocative species. Similar testing has been accomplished in those subjects suffering with RA, and IgA was not increased, even though it is certain that the intestinal integrity of those suffering with RA has been compromised largely to a similar extent as those suffering the other three conditions, possibly from the use of NSAIDs (2).
Persons with RA were almost certainly exposed to the K. pneumoniae the same way in which those with UC, CD, and AS are exposed, but they have no increased production of the antigen over the healthy control groups. This seems to indicate that, in persons who are susceptible to one of the three conditions, a considerable overproduction of IgA follows exposure to the K. pneumoniae antigen, like an allergic response, and the body is adversely affected by the excess IgA; the autoimmune reaction. Those with RA, have increased quantities of IgG to the bacteria p. mirabilis, while those with the three other conditions do not exhibit any increase in IgG production, although certainly these groups are exposed to this antigen, but likely from a different route (2).
It has been demonstrated that altering the normal diet to exclude foods which contain higher levels of starch, can significantly reduce the quantity of K. pneumoniae in the feces of all individuals (5). The implication is that the balance of intestinal florae can be altered to the extent that much fewer bacteria are available to cross the intestinal mucosa and elicit the production of IgA.
The low starch diet has been employed extensively in the treatment of AS at the AS Clinic located at Middlesex Hospital in London, under studies conducted by Dr Alan Ebringer (5). In these studies, significant reduction in IgA was obtained by reducing dietary starches by 40%, and a corresponding decrease in ESR was achieved by patients suffering from AS. This measure usually results in a considerable decrease of symptoms, typically unto effective remission. In patients unable to assiduously follow the low starch regimen, supplemental NSAID usage is required, however, most of the more recalcitrant cases could be treated using just the diet and the drug sulphasalazine. This has usually obviated the need for more powerful NSAIDs, avoiding their deleterious side effects (5).
Even after Carol Sinclair wrote her book, “The IBS Starch-Free Diet,”(6) she had not discovered that she actually had ankylosing spondylitis. AS is a disease which finds an incredibly diverse expression and severity level. Her complaint was Irritable Bowel Syndrome, which had been referred to as ‘spastic colon.’ Sufferers of AS often have the discomfort of Irritable Bowel Disease similar to chronic Ulcerative Colitis, or even Crohn’s Disease. These illnesses may, in fact, be interrelated, and it has been determined that elevated levels of IgA exist in all of these conditions(2).
After the many years of dietary experimentation, Carol arrived at a workable diet, which essentially eliminated all starches. She found that there were stages, and as certain types of starches were omitted, her own sensitivity to other kinds of starches actually increased until it was necessary to be on essentially a starch-free diet (6).
Upon typing for HLA B27, Carol found that she is positive, and has AS. Immediate family members have had AS, also, and it is especially instructive for everyone suffering with this disease to note well her dietary experiences. Lucky for the rest of us her system was sensitive to the extent of acting as a very useful early warning system.
In my own case, I can attest that elimination of starches is a quite effective treatment for AS, because I often eliminated starch—and everything except water, too: Fasting for periods usually lasting one week often allowed me to get out of a flare-up condition, and thereby control much of the pain associated with AS. Certainly, had I known of the starch connection, I could have gone for longer periods between this procedure and perhaps avoided some amount of the lasting damage; the spinal deformation from the calcification. Because of the irrefutable benefits, I will continue with periodic fasting, albeit it is now unnecessary in the control of my disease process at its present level.
In the context of starch and NSAIDs, I would like to add some pertinent details which could be useful in further studies. When I began taking NSAIDs regularly, I would often have bleeding from what I would term proctitis; an inflammation in the very lowest portion of the descending colon. This was evidenced by obvious, and sometimes considerable amounts of red blood on my toilet tissue. Sometimes there was slight cramping, and I usually knew whenever I was bleeding in this region. Because the NSAIDs caused this and severe stomach ulcers, I eventually ceased their use altogether and went on a prolonged fast, which actually allowed the ulcers to heal, and the bowel inflammation to be reduced. I refer to bowel lesions as ‘ulcerations,’ as opposed to stomach ulcers. They occur as a result of continued inflammation, especially in combination with older NSAIDs, which apparently prevent the healing process.
I have observed that, at my present status, I can still elicit similar bleeding by ingestion of high amounts of starch, even after having been NSAID-free for over two years; I have not taken even an aspirin in this period. Recently, I have been taking Cipro, an antibiotic, and I believe there is some minimal bleeding caused by this drug, also.
Diet is of extreme importance in controlling AS, and in milder cases can reduce the effects of the disease to the extent that no other measures are required. In most cases, some level of adjunctive therapy will likely be necessary, such as treatment using enteric coated sulphasalazine, or more common NSAIDs intermittently. Although antibiotics have been shown to facilitate elimination of K. pneumoniae, long term use is not recommended due to the potential for complications and standing contraindications.
Although starches likely are the best food source for K. pneumoniae, there is no doubt that this species has the ability to take up residence within bowel tissues and survive with extremely reduced food supply—waiting. Once the opportunity for multiplication is presented by the ingestion of starch, the bacteria quickly multiply and are carried along in the digesting food into intestinal lesions, for example, where they can most easily enter the bloodstream and cause production of IgA, which results in Ankylosing Spondylitis.
IgA/IgG: Immunoglobulin, an antibody. There are five basic types of Ig, characterized by their structure and differentiated by activity, and designated A, M, G, D, and E. Aside from the basic structural forms, they possess a keying site, which allows them to recognize a specific pathogen as a potentially dangerous invading agent. In the case of invasion from K. pneumoniae, the antibody we can call “IgA anti-K. pneumoniae” is manufactured, and its presence in all body fluids will increase. Generally, IgAs are found in greatest quantities in tears, saliva, and other excretory fluids, especially in the lubricating intestinal mucous. IgG is one of the most common antigen specific antibodies, and is the primary culprit in the autoimmune cycle for RA.
AAU: Acute Anterior Uveitis. An inflammatory condition which usually affects one eye at a time. The condition affects approximately 30% of persons who have AS, and some who do not and may be HLA B27 negative. This is a serious condition, and can damage the vision if left untreated, which should be unlikely due to the level of pain associated with AAU. Also called iritis.
CD: Crohn’s Disease. A severe inflammation of the small intestine, usually having characteristic deep and rounded lesions and appearing in two places, a primary location, and a secondary, less severe site. This is referred to as ‘segmentation.’ CD can be quite serious and low protein diets have been historically used in treatment, however, low starch diets seem to mitigate the condition, also.
AS: Ankylosing Spondylitis, technically means that the spine is calcifying. The disease is sometimes called poker spine, bamboo spine, Marie—Strumpel or Bechterew’s disease from the doctors who described the condition around the same time. There are specific guidelines for the determination of the disease, but typically X-rays are required to show the process of spinal fusion.
UC: Ulcerative Colitis is an inflammation of the colon which creates ‘ulcerations,’ usually elongated in nature and primarily affecting the first layers of the intestinal lining called the mucosa. Chronic UC can cause the condition of IBS due to the mucosa becoming permeable; leaky gut syndrome. This will sometimes dramatically affect the muscular peristaltic contractive forces by precipitating a reflex action in response to certain kinds of food or acid balance.
RA: Reactive Arthritis, often rheumatoid arthritis. Primary class of over 100 different distinctive diseases which usually have an autoimmune component, and often will lead to osteoarthritis, which is a deterioration of the joints. Often people who exhibit RA have the genotype indicated by HLA DR4 or HLA DR1.
NSAID: Non Steroidal Anti-inflammatory Drug, the primary substances in this category are aspirin, naproxen (Aleve), indomethacin (Indocin), sulindac (Clinoril), sulphasalazine (Azulfidine, Salzopyrene), etc. Newer, less damaging NSAIDs such as Celebrex, hold promise in the mitigation of AS with fewer side effects than the older drugs. All NSAIDs have risk associated with their use, and it is known that about 16,000 deaths annually in the US occur as a direct result of the use of powerful NSAIDs leading to spontaneous bleeding ulcer.
(1) ANKYLOSING SPONDYLITIS IS CAUSED BY KLEBSIELLA Evidence from Immunologic, Microbiologic, and Serologic Studies. Alan Ebringer, BSc. MD, FRCP, FRACP. Published under Spondyloarthropathies pp 105 through 121, Volume 18, number 1. February, 1992. In “Rheumatic Disease Clinics of North America.”
(2) ANTIBODY RESPONSES TO GUT BACTERIA IN ANKYLOSING SPONDYLITIS, RHEUMATOID ARTHRITIS, CROHN’S DISEASE, AND ULCERATIVE COLITIS H. Tiwana, C. Wilson, R.S. Walmsley, A. J. Wakefield, M. S. N. Smith, N. L. Cox, M. J. Hudson, A. Ebringer. Published in Rheumatology International Springer—Verlad. Article accepted 18 December, 1996.
(3) ANTIBODIES TO KLEBSIELLA PNEUMONIAE IN DUTCH PATIENTS WITH ANKYLOSING SPONDYLITIS AND ACUTE ANTERIOR UVEITIS AND TO PROTEUS MIRABILIS IN RHEUMATOID ARTHRITIS Sabine H. D. Blankenberg-Sprenkels, Mark Fielder, Theodorus E. W. Feltkamp, Harmale Tiwana, Clyde Wilson, and Alan Ebringer. “The Journal of Rheumatology 1998: 25:4.”
(4) ANTIBODIES TO KLEBSIELLA, PROTEUS, AND HLA B27 PEPTIDES IN JAPANESE PATIENTS WITH ANKYLOSING SPONDYLITIS AND RHEUMATOID ARTHRITIS Yoshitaka Tana, Harmale Tiwana, Sinsuke Hukuda, Junichi Nishioka, Mark Fielder, Clyde Wilson, Sukhvinder Bansal, and Alan Ebringer. Published in “The Journal of Rheumatology,” V 24, pp109-114, 1997.