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Raised incidence of ankylosing spondylitis among Inuit populations could be due to high HLA-B27 association and starch consumption

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Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis mainly affecting the spinal joints. It would appear that the most likely causative agent in the development of AS is an environmental factor in the genetically susceptible, HLA-B27 positive, individuals. Extensive data from several countries support the notion that Klebsiella pneumonia bacteria are the most likely culprit in the causation of AS. These microbes possess antigens which resemble HLA-B27 and spinal collagens. Increased intake of high-starch diet is directly proportional to the gut-associated bacterial load, especially in the large intestine, and among these microbial agents, Klebsiella is considered as one of the main constituting components. Therefore, a low-starch diet intake alongside the currently used medical therapeutic modalities could be beneficial in the management of patients with early AS. It is suggested that a change in the dietary habits from high protein, low-starch marine components to the Westernized high-starch diet among the Inuit peoples of Alaska and Canada could be considered as one of the main contributing factors in the increased prevalence of AS during the last few decades within this genetically unmixed native population.

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References

  1. Baeten D, Breban M, Lories R, Schett G, Sieper J (2013) Are spondylarthritides related but distinct conditions or a single disease with a heterogeneous phenotype? Arthritis Rheum 65:12–20

    Article  PubMed  Google Scholar 

  2. Haroon N, Inman RD (2010) Ankylosing spondylitis—new criteria, new treatments. Bull NYU Hosp Jt Dis 68:171–174

    PubMed  Google Scholar 

  3. Brewerton DA, Hart FD, Nicholls A, Cafferty M, James DC, Sturrock RD (1973) Ankylosing spondylitis and HL-A 27. Lancet i:904–907

    Article  Google Scholar 

  4. Schlosstein L, Terasaki PI, Bluestone E, Pearson CM (1973) High association of an HLA antigen, W27, with ankylosing spondylitis. N Engl J Med 288:704–706

    Article  CAS  PubMed  Google Scholar 

  5. Robinson PC, Brown MA (2014) Genetics of ankylosing spondylitis. Mol Immunol 57:2–11

    Article  CAS  PubMed  Google Scholar 

  6. Inman R (2008) The spondyloarthropathies. In: Goldman L, Ansiello D (eds) Cecil medicine, 23rd edn. Saunders-Elsevier, Philadelphia, pp 2014–2021

    Google Scholar 

  7. Rashid T, Ebringer A (2011) Gut-mediated, and HLA-B27-associated arthritis: an emphasis on ankylosing spondylitis and Crohn’s disease with a proposal for the use of new treatment. Discov Med 12:187–194

    PubMed  Google Scholar 

  8. Baines M, Ebringer A, Avakian H, Samuel D, James DC (1990) The use of enzyme immunoassay (EIA) and radiobinding assay to investigate the cross-reactivity of Klebsiella antigens and HLA-B27 in ankylosing spondylitis patients and healthy controls. Scand J Rheumatol 19:341–349

    Article  CAS  PubMed  Google Scholar 

  9. Gonzalez-Roces S, Alvarez MV, Gonzalez S, Dieve A, Makni H, Woodfield DG, Housan L, Konenkov V, Abbadi MC, Grunnet N, Coto E, Lopez-Larrea C (1997) HLA-B27 polymorphism and worldwide susceptibility to ankylosing spondylitis. Tissue Antigens 49:116–123

    Article  CAS  PubMed  Google Scholar 

  10. Benevolenskaia LI, Erdes SH, Krylov MI, Chekalina NA (1994) The epidemiology of spondyloarthropathies among the native inhabitants of Chukotka. 2. The prevalence of HLA-B27 in the population and among spondyloarthropathy patients. Ter Arkh 66:41–44

    CAS  PubMed  Google Scholar 

  11. Alexeeva L, Krylov M, Vturin V, Mylov N, Erdesz S, Benevolenskava L (1994) Prevalence of spondyloarthropathies and HLA-B27 in the native population of Chukotka, Russia. J Rheumatol 21:2298–2300

    CAS  PubMed  Google Scholar 

  12. Rashid T, Ebringer A (2007) Ankylosing spondylitis is linked to Klebsiella—the evidence. Clin Rheumatol 26:858–864

    Article  PubMed  Google Scholar 

  13. Pedersen OB, Svendsen AJ, Ejstrup L, Skytthe A, Harris JR, Junker P (2008) Ankylosing spondylitis in Danish and Norwegian twins: occurrence and the relative importance of genetic vs. environmental effectors in disease causation. Scand J Rheumatol 37:120–126

    Article  CAS  PubMed  Google Scholar 

  14. Ebringer A, Cowling P, Ngwa-Suh N, James DCO, Ebringer RW (1976) Cross-reactivity between Klebsiella aerogenes species and B27 lymphocyte antigens as an aetiological factor in ankylosing spondylitis. In: Dausset J, Svegaard A (eds) HLA and disease. INSERM, Paris, pp 27–31

    Google Scholar 

  15. Avakian H, Welsh J, Ebringer A, Entwistle CC (1980) Ankylosing spondylitis, HLA-B27 and Klebsiella. II. Cross-reactivity studies with human tissue typing sera. Br J Exp Pathol 61:92–96

    PubMed Central  CAS  PubMed  Google Scholar 

  16. Ogasawara M, Kono DH, Yu DT (1986) Mimicry of human histocompatibility HLA-B27 antigens by Klebsiella pneumoniae. Infect Immun 51:901–908

    PubMed Central  CAS  PubMed  Google Scholar 

  17. Schwimmbeck PL, Yu DT, Oldstone MB (1987) Autoantibodies to HLA-B27 in the sera of HLA-B27 patients with ankylosing spondylitis and Reiter’s syndrome: molecular mimicry with Klebsiella pneumoniae as potential mechanism of autoimmune disease. J Exp Med 166:173–181

    Article  CAS  PubMed  Google Scholar 

  18. Fielder M, Pirt SJ, Tarpey I, Wilson C, Cunningham P, Ettelaie C, Binder A, Bansal S, Ebringer A (1995) Molecular mimicry and ankylosing spondylitis: possible role of a novel sequence in pullulanase of Klebsiella pneumoniae. FEBS Lett 369:243–248

    Article  CAS  PubMed  Google Scholar 

  19. Rashid T, Ebringer A (2012) Detection of Klebsiella antibodies and HLA-B27 allelotypes could be used in the early diagnosis of ankylosing spondylitis with a potential for the use of “low starch diet” in the treatment. Curr Rheumatol Rev 8:109–119

    Article  CAS  Google Scholar 

  20. Stone MA, Payne U, Schentag C, Rahman P, Pacheco-Tena C, Inman RD (2004) Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis. Rheumatology (Oxford) 43:148–155

    Article  CAS  Google Scholar 

  21. Tani Y, Tiwana H, Hukuda S, Nishioka J, Fielder M, Wilson C, Bansal S, Ebringer A (1997) Antibodies to Klebsiella, Proteus and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis. J Rheumatol 24:109–114

    CAS  PubMed  Google Scholar 

  22. Husby G, Tsuchiya N, Schwimmbeck PL, Keat A, Pahle JA, Oldstone MB, Williams RC Jr (1989) Cross-reactive epitope with Klebsiella pneumoniae nitrogenase in articular tissue of HLA-B27+ patients with ankylosing spondylitis. Arthritis Rheum 32:437–445

    Article  CAS  PubMed  Google Scholar 

  23. Wilson C, Rashid T, Tiwana H, Beyan H, Hughes L, Bansal S, Ebringer A, Binder A (2003) Cytotoxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondylitis. J Rheumatol 30:972–978

    CAS  PubMed  Google Scholar 

  24. Hascelik G, Oz B, Olmez N, Memis A, Yoruk G, Unsal B, Ekinci N (2009) Association of macroscopic gut inflammation with disease activity, functional status and quality of life in ankylosing spondylitis. Rheumatol Int 29:755–758

    Article  PubMed  Google Scholar 

  25. Jacques P, Elewaut D, Mielants H (2010) Interactions between gut inflammation and arthritis/spondylitis. Curr Opin Rheumatol 22:368–374

    Article  PubMed  Google Scholar 

  26. Bjarnason I, Helgason KO, Geirsson AJ, Sigthorsson G, Reynisdottir I, Gudbjartsson D, Einarsdottir AS, Sherwood R, Kristjansson K, Kjartansson O, Thjodleifsson B (2003) Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis. Gastroenterology 125:1598–1605

    Article  PubMed  Google Scholar 

  27. Hunter T, Harding GK, Kaprove RE, Schroeder ML (1981) Fecal carriage of various Klebsiella and Enterobacter species in patients with active ankylosing spondylitis. Arthritis Rheum 24:106–108

    Article  CAS  PubMed  Google Scholar 

  28. Kuberski TT, Morse HG, Rate RG, Bonnell MD (1983) Increased recovery of Klebsiella from the gastrointestinal tract of Reiter’s syndrome and ankylosing spondylitis patients. Br J Rheumatol 22(Suppl. 2):85–90

    Article  Google Scholar 

  29. Kujath K, Kekow M, Drynda S, Podschun R, Sahly H, Kekow J (2001) The presence of Klebsiella in feces and smears in patients with and without ankylosing spondylitis—isolation of multiple Klebsiella species and K serotypes. Arthritis Rheum 44(Suppl 9):S1103

    Google Scholar 

  30. Ebringer R, Cooke D, Cawdell DR, Cowling P, Ebringer A (1977) Ankylosing spondylitis: Klebsiella and HLA-B27. Rheumatol Rehabil 16:190–196

    Article  CAS  PubMed  Google Scholar 

  31. Eastmond CJ, Willshaw HE, Burgess SE, Shinebaum R, Cooke EM, Wright V (1980) Frequency of faecal Klebsiella aerogenes in patients with ankylosing spondylitis and controls with respect to individual features of the disease. Ann Rheum Dis 39:118–123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Maki-Ikola O, Leirisalo-Repo M, Turunen U, Granfors K (1997) Association of gut inflammation with increased serum IgA class Klebsiella antibody concentrations in patients with axial ankylosing spondylitis (AS): implication for different aetiopathogenetic mechanisms for axial and peripheral AS? Ann Rheum Dis 56:180–183

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Maki-Ikola O, Hallgren R, Kanerud L, Feltelius N, Knutsson L, Granfors K (1997) Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis. Ann Rheum Dis 56:421–425

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Burke RJ, Chang C (2014) Diagnostic criteria of acute rheumatic fever. Autoimmun Rev 13:503–507

    Article  PubMed  Google Scholar 

  35. Anderson IH, Levine AS, Levitt MD (1981) Incomplete absorption of carbohydrate in all-purpose wheat flour. New Engl J Med 304:891–892

    Article  CAS  PubMed  Google Scholar 

  36. Barnett AM, Roy NC, McNabb WC, Cookson AL (2012) The interactions between endogenous bacteria, dietary components and the mucus layer of the large bowel. Food Funct 3:690–699

    Article  CAS  PubMed  Google Scholar 

  37. Lin Q, Huang B, Zhang M, Zhang X, Rivenbark J, Lappe RL, James MG, Myers AM, Hennen-Bierwagen TA (2012) Functional interactions between starch synthase III and isoamylase-type starch-debranching enzyme in maize endosperm. Plant Physiol 158:679–692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Higgins JA (2014) Resistant starch and energy balance: impact on weight loss and maintenance. Crit Rev Food Sci Nutr 54:1158–1166

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Ciccia F, Alessandro R, Rizzo A, Accardo-Palumbo A, Raimondo S, Raiata F, Guggino G, Giardina A, De Leo G, Sireci G, Triolo G (2014) Macrophage phenotype in the subclinical gut inflammation of patients with ankylosing spondylitis. Rheumatology (Oxford) 53:104–113

    Article  CAS  Google Scholar 

  40. Calguneri M, Swinburne L, Shinebaum R, Cooke EM, Wright V (1981) Secretory IgA: immune defence pattern in ankylosing spondylitis and Klebsiella. Ann Rheum Dis 40:600–604

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Trull AK, Panayi GS (1983) Serum and secretory IgA immune response to Klebsiella pneumonia in ankylosing spondylitis. Clin Rheumatol 2:331–337

    Article  CAS  PubMed  Google Scholar 

  42. Tani Y, Sato H, Tanaka N, Mori K, Doida Y, Hukuda S (1997) Serum IgA1 and IgA2 subclass antibodies against collagens in patients with ankylosing spondylitis. Scand J Rheumatol 26:380–382

    Article  CAS  PubMed  Google Scholar 

  43. Ebringer A, Wilson C (1996) The use of low starch diet in the treatment of patients suffering from ankylosing spondylitis. Clin Rheumatol 15(Suppl l):62–66

    Article  PubMed  Google Scholar 

  44. Ebringer A, Baines M, Childerstone M, Ghuloom M, Ptaszynska T (1985) Etiopathogenesis of ankylosing spondylitis and the cross-tolerance hypothesis. In: Ziff M, Cohen SB (eds) Advances in inflammation research—the spondyloarthropathies. Raven Press, New York, pp 101–128

    Google Scholar 

  45. Oh BR, Seo JW, Heo SY, Hong WK, Luo LH, Son JH, Park DH, Kim CH (2012) Fermentation strategies for 1,3-propanediol production from glycerol using a genetically engineered Klebsiella pneumonia strain to eliminate by-product formation. Bioprocess Biosyst Eng 35:159–165

    Article  CAS  PubMed  Google Scholar 

  46. Michaelis S, Chapon C, D’Enfert C, Pugsley AP, Schwartz M (1985) Characterization and expression of the structural gene for pullulanase, a maltose-inducible secreted protein of Klebsiella pneumonia. J Bacteriol 164:633–638

    PubMed Central  CAS  PubMed  Google Scholar 

  47. Finegold SM, Sutter VL, Sugihara PT, Elder HA, Lehmann SM, Philips RL (1977) Fecal microbial flora in Seventh Day Adventist populations and control subjects. Am J Clin Nutr 30:1781–1792

    CAS  PubMed  Google Scholar 

  48. Bakland G, Nossent HC, Gran JT (2005) Incidence and prevalence of ankylosing spondylitis in Northern Norway. Arthritis Rheum 53:850–855

    Article  PubMed  Google Scholar 

  49. Van der Heijde D, Sieper J, Maksymowych WP, Brown MA, Lambert RG, Rathmann SS, Pangan AL (2014) Spinal inflammation in the absence of sacroiliac joint inflammation on magnetic resonance imaging in patients with active nonradiographic axial spondyloarthritis. Ann Rheum Dis 66:667–673

    Google Scholar 

  50. Gadsby P (2004) The Inuit Paradox. Health, Medicine and Nutrition. www.discovermagazine.com. Oct. Issue, http://discovermagazine.com/2004/oct/inuit-paradox#.UqSLT9JDtAo

  51. Sharma S (2010) Assessing diet and lifestyle in the Canadian Arctic Inuit and Inuvialuit to inform a nutrition and physical activity intervention programme. J Hum Nutr Diet 23(Suppl 1):5–17

    Article  PubMed  Google Scholar 

  52. Gofton JP, Chalmers A, Price GE, Reeve CE (1984) HL-A27 and ankylosing spondylitis in B.C. Indians. J Rheumatol 11:572–573

    CAS  PubMed  Google Scholar 

  53. Boyer GS, Templin DW, Lanier AP (1991) Rheumatic diseases in Alaskan Indians of the southeast coast: high prevalence of rheumatoid arthritis and systemic lupus erythematosus. J Rheumatol 18:1477–1484

    CAS  PubMed  Google Scholar 

  54. Hansen JA, Lanier AP, Nisperos B, Mickelson E, Dahlberg S (1986) The HLA system in Inupiat and central Yupik Alaskan Eskimos. Hum Immunol 16:315–328

    Article  CAS  PubMed  Google Scholar 

  55. Boyer GS, Lanier AP, Templin DW (1988) Prevalence rates of spondyloarthropathies, rheumatoid arthritis, and other rheumatic disorders in an Alaskan Inupiat Eskimo population. J Rheumatol 15:678–683

    CAS  PubMed  Google Scholar 

  56. Oen K, Posti B, Chalmers IM, Ling N, Schroeder ML, Baragar FD, Martin L, Reed M, Major P (1986) Rheumatic diseases in an Inuit population. Arthritis Rheum 29:65–74

    Article  CAS  PubMed  Google Scholar 

  57. Geirsson AJ, Eyiolfsdottir H, Biornsdottir G, Kristjansson K, Gudbjornsson B (2010) Prevalence and clinical characteristics of ankylosing spondylitis in Iceland—a nationwide study. Clin Exp Rheumatol 28:333–340

    PubMed  Google Scholar 

  58. Erdesz S, Shubin SV, Shock BP, Krylov MY, Mylov NM, Chekalina NA, Benevolenskaya LI (1994) Spondyloarthropathies in circumpolar populations of Chukotka (Eskimos and Chukchi): epidemiology and clinical characteristics. J Rheumatol 21:1101–1104

    CAS  PubMed  Google Scholar 

  59. Krylov M, Erdesz S, Alexeeva L, Benevolenskaya L, Arnett FC, Reveille JD (1995) HLA class II and HLA-B27 oligotyping in two Siberian native population groups. Tissue Antigens 46:382–386

    Article  CAS  PubMed  Google Scholar 

  60. Gran JT, Husby G, Hordvik M (1985) Prevalence of ankylosing spondylitis in males and females in a young middle-aged population of Tromso, Northern Norway. Ann Rheum Dis 44:359–367

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. Khan MA (1995) HLA-B27 and its subtypes in world populations. Curr Opin Rheumatol 7:263–269

    Article  CAS  PubMed  Google Scholar 

  62. Johnsen K, Gran JT, Dale K, Husby G (1992) The prevalence of ankylosing spondylitis among Norwegian Samis (Lapps). J Rheumatol 19:1591–1594

    CAS  PubMed  Google Scholar 

  63. Peschken CA, Esdaile JM (1999) Rheumatic diseases in North America’s indigenous peoples. Semin Arthritis Rheum 28:368–391

    Article  CAS  PubMed  Google Scholar 

  64. Brown MA, Jepson A, Young A, Whittle HC, Greenwood BM, Wordsworth BP (1997) Ankylosing spondylitis in West African—evidence for a non-HLA-B27 protective effect. Ann Rheum Dis 56:68–70

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank the Trustees of the Middlesex Hospital, the Arthritis Research Campaign and the “American Friends of King’s College London” for their financial supports.

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The authors declare that they have no conflict of interests.

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Correspondence to Alan Ebringer.

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Rashid, T., Wilson, C. & Ebringer, A. Raised incidence of ankylosing spondylitis among Inuit populations could be due to high HLA-B27 association and starch consumption. Rheumatol Int 35, 945–951 (2015). https://doi.org/10.1007/s00296-014-3164-2

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