Molecular Mimicry, the Hygiene Hypothesis, Stealth Infections and Other Examples of Disconnect between Medical Research and the Practice of Clinical Medicine in Autoimmune Disease


Autoimmune disorders have been on a steep rise in the industrialized countries over the past several decades and while research has been starting to develop a detailed understanding of pathophysiology and many of the underlying mechanisms, any meaningful incorporation of this information into clinical medicine has been painfully slow. Concepts of molecular mimicry, the hygiene hypothesis, intestinal hyper-permeability (leaky gut syndrome) and aggressive use of predictive antibody testing are explored in this article with examples given on how emerging information on these phenomena may aid the clinician in a new, more proactive, approach to management of these conditions.

Share and Cite:

D. Brady, "Molecular Mimicry, the Hygiene Hypothesis, Stealth Infections and Other Examples of Disconnect between Medical Research and the Practice of Clinical Medicine in Autoimmune Disease," Open Journal of Rheumatology and Autoimmune Diseases, Vol. 3 No. 1, 2013, pp. 33-39. doi: 10.4236/ojra.2013.31007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] J. F. Bach, “The Effect of Infections on Susceptibility to Autoimmune and Allergic Diseases,” The New England Journal of Medicine, Vol. 347, No. 12, 2002, pp. 911-920. doi:10.1056/NEJMra020100
[2] M. Inaba, S. Ushijim, N. Hirata, et al., “Methotrexate-Related Lyphomatoid Granulomatosis in a Patient with Rheumatoid Arthritis,” Nihon Kokyuki Gakkai Zasshi, Vol. 49, No. 8, 2011, pp. 597-601.
[3] M. D. Mayes, “Epidemiologic Studies of Environmental Agents and Systemic Autoimmune Diseases,” Environmental Health Perspectives, Vol. 107, Supplement 5, 1999, pp. 743-748
[4] O. V. Pishak, “Bukovian State Medical Academy, Public Health Ministry of Ukraine,” Mikrobiolohichnyi Zhurnal, Vol. 61, No. 5, 1999, pp. 41-47.
[5] H. Tiwana, C. Wilson, R. S. Walmsley, et al., “Antibody Responses to Gut Bacteria in Ankylosing Spondylitis, Rheumatoid Arthritis, Crohn’s Disease and Ulcerative Colitis,” Rheumatology International, Vol. 17, No. 1, 1997, pp. 11-16. doi:10.1007/PL00006845
[6] A. Ebringer and T. Rahid, “Rheumatoid Arthritis Is an Autoimmune Disease Triggered by Proteus Urinary Tract Infection,” Clinical and Developmental Immunology, Vol. 13, No. 1, 2006, pp. 41-48. doi:10.1080/17402520600576578
[7] A. Ebringer, T. Rahid and C. Wilson, “Rheumatoid Arthritis: Proposal for the Use of Anti-Microbial Therapy in Early Cases,” Scandinavian Journal of Rheumatology, Vol. 32, No. 1, 2003, pp. 2-11. doi:10.1080/03009740310000337
[8] F. Liao, Z. Li, Y. Wang, et al., “Porphyromonas Gingivalis May Play an Important Role in the Pathogenesis of Periodontitis-Associated Rheumatoid Arthritis,” Medical Hypotheses, Vol. 72, No. 6, 2009, pp. 732-735.
[9] M. Harkiolaki, S. L. Holmes, P. Svendsen, et al., “T-Cell-Mediated Autoimmune Disease Due to Low-Affinity Cross Reactivity to Common Microbial Peptides,” Immunity, Vol. 30, No. 3, 2009, pp. 348-357. doi:10.1016/j.immuni.2009.01.009
[10] S. K. Mazmanian, J. L. Round and D. L. Kasper, “A Microbial Symbiosis Factor Prevents Intestinal Inflammatory Disease,” Nature, Vol. 453, No. 7195, 2008, pp. 620-625. doi:10.1038/nature07008
[11] G. Petru, D. Stunzner, P. Lind, et al., “Antibodies to Yersinia Enterocolitica in Immunogenic Thyroid Diseases,” Acta Medica Austriaca, Vol. 14, No. 1, 1987, pp. 11-14.
[12] N. Anasaldi, T. Palmas, A. Corrias, et al., “Autoimmune Thyroid Disease and Celiac Disease in Children,” Journal of Pediatric Gastroenterology and Nutrition, Vol. 37, No. 1, 2003, pp. 63-66. doi:10.1097/00005176-200307000-00010
[13] D. Brady, “Novel Options in GI Diagnostics: DNA Detection of Gut Microbiota,” Complementary Medicine, 2008, pp. 28-31.
[14] S. T. Weiss, “Eat Dirt—The Hygiene Hypothesis and Allergic Disease (Editorial),” The New England Journal of Medicine, Vol. 347, No. 12, 2002, pp. 930-931. doi:10.1056/NEJMe020092
[15] E. von Mutius and D. Vercelli, “Farm Living: Effects on Childhood Asthma and Allergy,” Nature Reviews Immunology, Vol. 10, No. 12, 2010, pp. 861-868. doi:10.1038/nri2871
[16] D. Gutierrez, “Parasites in Your Gut Actually Help Protect You from Allergies,” NaturalNews, 2011.
[17] R. W. Summers, D. E. Elliott, J. V. Weinstock, et al., “Trichuris Suis Seems to Be Safe and Possibly Effective in the Treatment of Inflammatory Bowel Disease,” The American Journal of Gastroenterology, Vol. 98, No. 9, 2003, pp. 2034-2041. doi:10.1111/j.1572-0241.2003.07660.x
[18] A Fasano and T. Shea-Donohue, “Mechanisms of Disease: The Role of Intestinal Barrier Function in the Pathogenesis of Gastrointestinal Autoimmune Diseases,” Nature Clinical Practice Gastroenterology & Hepatology, Vol. 2, No. 9, 2005, pp. 416-422. doi:10.1038/ncpgasthep0259
[19] A. Fasano, “Surprises from Celiac Disease,” Scientific American, Vol. 301, No. 2, 2009, pp. 54-61. doi:10.1038/scientificamerican0809-54
[20] A. Sapone, L. de Magistris and M. Pietzak, “Zonulin Upregulation Is Associated with Increased Gut Permeability in Subjects with Type I Diabetes and Their Relatives,” Diabetes, Vol. 55, No. 5, 2006, pp. 1443-1449. doi:10.2337/db05-1593
[21] J. Kong, Z. Zhang, M. W. Musch, et al., “Novel Role of the Vitamin D Receptor in Maintaining the Integrity of the Intestinal Mucosal Barrier,” American Journal of Physiology—Gastrointestinal and Liver Physiology, Vol. 294, No. 1, 2008, pp. G208-G216. doi:10.1152/ajpgi.00398.2007
[22] S. Y. Yao, C. W. Stratton and W. M. Mitchell, “CSF Oligoclonal Bands in MS Include Antibodies against Chlamydophilia Antigens,” Neurology, Vol. 56, No. 9, 2001, pp. 1168-1176. doi:10.1212/WNL.56.9.1168
[23] D. H. Gilden, “Infectious Causes of Multiple Sclerosis,” The Lancet Neurology, Vol. 4, No. 3, 2005, pp. 195-202.
[24] A. F. Gombart, N. Borregaard and H. P. Koeffler, “Human Cathelicidin Antimicrobial Peptide (Camp) Gene Is a Direct Target of the Vitamin D Receptor and Is Strongly Up-Regulated in Myeloid Cells by 1,25-Hihydroxyvitamin D3,” Future Microbiology, Vol. 4, No. 9, 2009, pp. 1151-1165. doi:10.2217/fmb.09.87
[25] A. L. Notkins, “New Predictors of Disease,” Scientific American, Vol. 296, No. 3, 2007, pp. 72-79. doi:10.1038/scientificamerican0307-72
[26] D. Leslie, P. Lipsky and A. L. Notkins, “Autoantibodies as Predictors of Disease,” Journal of Clinical Investigation, Vol. 108, No. 10, 2001, pp. 1417-1422.
[27] T. O’Bryan, “American College for Advancement in Medicine Annual Symposium Presentation 2009”.
[28] Y. Shoenfeld, M. Blank, M. Abu-Shakra, et al., “The Mosaic of Autoimmunity: Prediction, Autoantibodies, and Therapy in Autoimmune Disease,” IMAJ, Vol. 10, No. 1, 2008, pp. 13-19.
[29] B. Lindberg, S. A. Iverson, et al., “Islet Autoantibodies in Cord Blood in Children Who Develop Type I (Insulin-Dependent) Diabetes Mellitus before 15 Years of Age,” Diabeteologia, Vol. 42, No. 2, 1999, pp. 181-187. doi:10.1007/s001250051137
[30] A. Vojdani, “Antibodies as Predictors of Complex Autoimmune Diseases and Cancer,” International Journal of Immunopathology and Pharmacology, Vol. 21, No. 3, 2008, pp. 553-566.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.