Ankylosing Spondylitis Diary and Diet Research

ANKYLOSING SPONDYLITIS

Ankylosing spondylitis (AS) affects approximately 1/2 million people in the U.K. and some 96% of them possess HLA-B27, whilst the frequency of this antigen in the general population is about 8%. In 1975, we started our studies on AS and proposed that AS patients were infected clinically or sub-clinically by a microbe which carried antigens crossreacting with HLA-B27. Studies with rabbit antisera and human tissue typing sera demonstrated that HLA-B27 carried antigens which crossreacted with antigens found in Klebsiella microorganisms. Clinical studies showed that AS patients during active phases of the disease,had increased quantities of fecal Klebsiella and increased IgA antibody levels against Klebsiella microbes. Specific antibody elevations to Klebsiella microbes have now been reported from the following countries: England, Scotland, Finland, Germany, USA, Canada, Slovakia, Sweden, Spain, Mexico, Japan, Australia, The Netherlands and Argentina. Furthermore molecular mimicry has been demonstrated between Klebsiella pneumoniae pulD secretion protein (DRDE) and HLA-B27 (DRED). A second molecular mimicry crossreactivity has been demonstrated between Klebsiella pulA (pullulanase) enzyme (Gly-X-Pro) and types I,III and IV collagens, thereby providing a possible explanation for the localization of the disease to the spine, large joints and uvea. AS patients have antibodies against self-peptides containing the HLA-B27 crossreacting sequences, thereby making AS an autoimmune disease. These results are consistent with the hypothesis that AS is an autoimmune reactive arthritis following Klebsiella infection of the gut, around the ileo-caecal junction. Bowel flora mass depends on high intakes of starch and therefore the "London AS diet", consisting of a low intake of starch (No bread, cakes, potatoes and pasta) has been used in the treatment of AS patients at the Middlesex Hospital with relative success since 1982. This has led to a reduction in the quantity of NSAID's required for alleviating symptoms.

Related References:
Ebringer et al. (1976) Crossreactivity between Klebsiella aerogenes species and B27 lymphocyte antigens as an aetiological factor in ankylosing spondylitis. In "HLA and disease".Ed.Dausset & Svejgaard. INSERM Vol.58.Pg.27.
Ebringer and Wilson (1996) The use of a low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clin Rheumatol Vol.15. Suppl.2. Pg:62-66.
Tani et al. (1997) Antibodies to Klebsiella, Proteus and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis. Journal of Rheumatol Vol 24. Pg:109-114.

 

CROHN'S DISEASE

Crohn's disease is an inflammatory condition of the small bowel, around the ileo-caecal junction characterized by thickenings of the bowel sub-mucosa, leading to recurrent abdominal pains and eventually bowel obstruction. The majority of Crohn's disease patients are NEGATIVE for HLA-B27. However serological studies have demonstrated that during active phases of the disease, most Crohn's disease patients have elevated levels of specific antibodies to Klebsiella microorganisms. It is proposed that Crohn's disease occurs as a result of a Klebsiella infection in the ileo-caecal region of the gut, in patients who are HLA-B27 NEGATIVE. The Klebsiella membrane antigens are "fibrogenic" and thus cause thickenings of the bowel mucosa. The general theory is proposed that HIGH STARCH eaters may develop 2 types of diseases, depending on their HLA-status: Those that are HLA-B27 POSITIVE will develop AS and those that are HLA-B27 NEGATIVE will develop Crohn's disease. Prospective dietary studies should be carried out to determine the effectiveness or otherwise of a "LOW STARCH DIET" either in AS or Crohn's disease.

Related References:
Tiwana et al. (1997) Antibody responses to gut bacteria in AS, RA, Crohn's disease and ulcerative colitis. Rheum Internat Vol.17. Pg:11-16.

 

RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) affects approximately 1 million people in the U.K. and women are 3 to 4 times more likely to be affected than men. Over 90% of RA patients with severe disease carry either HLA-DR1 or some subtypes of HLA-DR4, incorporating the susceptibility sequence EQRRAA. Since our studies in AS had been successful and led to the proposal that Klebsiella microbes carried antigens crossreacting with HLA-B27, a similar approach was adopted for RA in 1980. Studies with rabbit antisera and tissue typing sera demonstrated that HLA-DR4 carried antigens which crossreacted with bacterial antigens found in Proteus mirabilis microbes. Since Proteus infection of the upper urinary tract is commoner in women than men, this could explain the higher prevalence of RA in women. Elevated levels of antibodies to Proteus mirabilis have been reported from the U.K. (London, Epsom, Stevenage, Winchester, Newcastle, Dundee), Ireland (Dublin), France (Brest and Toulouse), Spain (Barcelona),Japan (Otsu and Tokyo), The Netherlands (Amsterdam),Finland (Helsinki) and Bermuda (Hamilton). Computer analysis identified the sequence ESRRAL found in Proteus haemolysin which showed molecular mimicry with the EQRRAA susceptibility sequence.
Biochemical studies demonstrated that RA patients had antibodies to both EQRRAA/ESRRAL sequences.
Further molecular studies identified a second similarity sequence IRRET, present in Proteus urease which showed molecular mimicry with the LRREI sequence found in type XI collagen, a common component of hyaline cartilage. Since erosions of hyaline cartilage are frequently found in RA patients, especially in the small joints of the hands and feet, this could explain the localization of the pathological lesions in this disease to these sites.
These results are consistent with the hypothesis that RA is an autoimmune reactive arthritis following infection of the upper urinary tract by Proteus mirabilis microbes.
The value of anti-Proteus therapy in RA should be evaluated by prospective multi-centre, double-blind, controlled trials.

Related References:
Tiwana et al. (1996) Antibodies to 4 Gram-negative bacteria which share sequences with the RA susceptibility motif. Brit J Rheum Vol.35.Pg:592-594
Wilson et al. (1997) Correlation between anti-Proteus antibodies and isolation rates of Proteus mirabilis in RA. J Rheumatol Vol.16. Pg:109-14. 

"Bone health is substantially dependent on dietary acid/base balance.  All foods upon digestion ultimately must report to the kidney as either acid or base.  When the diet yields a net acid load (such as low-carb fad diets that restrict consumption of fruits and vegetables), the acid must be buffered by the alkaline stores of base in the body.  Calcium salts in the bones represent the largest store of alkaline base in the body and are depleted and eliminated in the urine when the diet produces a net acid load.  The highest acid-producing foods are hard cheeses, cereal grains, salted foods, meats, and legumes, whereas the only alkaline, base-producing foods are fruits and vegetables.  Because the average American diet is overloaded with grains, cheeses, salted processed foods, and fatty meats at the expense of fruits and vegetables, it produces a net acid load and promotes bone de-mineralization.  "

"We do have a very convincing chart (Tzero-before and Tnine months-after, are the two examination points; instructions were 'reduce starch consumption as much as comfortable for you'):

"The majority of persons with AS, indicate activity through ESR, however, even those who do not 'indicate' have reported success by restricting starches, as well as HLA B27 negative individuals.

"The chart shows that two persons actually increased ESR by restricting starch and one did not change at all. Of course, I cannot help making a connection between one contrary-slope and the guy who ate a potato every night with dinner, later ratted out by his son, also a patient. I wonder whether father tried telling son that the diet did not work for him!

"But the more obvious and important issue is the extrapolation to pain relief: Depending upon where they began, some of these subjects will not have noticed very much improvement even after nine months on a restricted starch diet. ESR decreasing from 65 to 48, for example, does very little obvious good unless I know what the numbers are, and it would take another nine months for ESR to drop low enough to feel the difference the diet makes. Since so many people do not indicate in the first place, this makes success on the diet a rather subjective thing.

"This chart helped me decide to be more radical and reduce all starches possible, and also test Ebringer's work another step by taking antibiotics at the same time. And although I did not believe in a linear relationship between starch and AS activity, I did begin to realize that any effort in elimination will pay off somewhat, if not in exact proportions."