International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: Editor-in-chief: Samasca Gabriel
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International Journal of Celiac Disease. 2020, 8(1), 10-21
DOI: 10.12691/ijcd-8-1-3
Open AccessArticle

Bovine Milk Proteins as a Trigger for Autoimmune Diseases: Myth or Reality?

Vânia Vieira Borba1, 2, Aaron Lerner3, , Torsten Matthias3 and Yehuda Shoenfeld4, 5

1Department ‘A’ of Internal Medicine, Coimbra University Hospital Centre, Coimbra, Portugal

2Faculty of Medicine, University of Coimbra, Coimbra, Portugal;Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel

3Aesku.KIPP Institute, Wendelsheim, Germany

4Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel

5ackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

Pub. Date: April 27, 2020

Cite this paper:
Vânia Vieira Borba, Aaron Lerner, Torsten Matthias and Yehuda Shoenfeld. Bovine Milk Proteins as a Trigger for Autoimmune Diseases: Myth or Reality?. International Journal of Celiac Disease. 2020; 8(1):10-21. doi: 10.12691/ijcd-8-1-3


Humans started to drinkmammal’s milk 11,000 years ago. Nowadays, cow, goat and sheep milks account for about 87% of the world milk production. The high incidence of allergies to cow’s milk components and autoimmune diseases is rising in the Western industrialized countries, where milk is a major dietary component, especially in processed foods. When allergenic milk proteins face immature and susceptible immune system in children it might represent a threat for future health. Several studies support strong evidences that exposure to dietary allergens during childhood can increase the risk of developing autoimmune diseases, such as type 1 diabetes, celiac disease, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, neuropsychiatric disorders, among others. The "Mosaic of Autoimmunity" elucidates the diversity and multifactorial origin of autoimmune disease expression in humans. Growing evidence suggests a large overlap between oral tolerance, food antigens and autoimmune diseases. Assorted mechanisms have been hypothesized to explain the connection between these entities, mainly involving molecular mimicry, shared epitopes, cross-reactivity phenomena, enhanced hosts gut permeability, change in microbiome/ dysbiome ratio and even involving Mycobacterium avium subspecies paratuberculosis infection. Nowadays, different kinds of milk and dairy products are being evaluated for a potential benefit in human health. Likewise, milk derived nutraceutical products, such as bovine colostrum, claim many clinical advantages especially for its immune modulatory capabilities. The aim of this review is to explore the impact of cow’s milk protein son human health, emphasizing its relationship with immune mediated and autoimmune diseases.

milk autoimmune diseases autoimmunity food allergy immune tolerance type 1 diabetes rheumatoid arthritis multiple sclerosis

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[1]  Curry A. Archaeology: The milk revolution. Nature. 2013; 500: 20-2.
[2]  Ziegler EE. Adverse effects of cow's milk in infants. Nestle Nutr Workshop Ser Pediatr Program. 2007; 60: 185-96; discussion 96-9.
[3]  Molina V, Shoenfeld Y. Infection, vaccines and other environmental triggers of autoimmunity. Autoimmunity. 2005; 38: 235-45.
[4]  Shoenfeld Y, Isenberg DA. The mosaic of autoimmunity. Immunology today. 1989; 10: 123-6.
[5]  de Carvalho JF, Pereira RM, Shoenfeld Y. The mosaic of autoimmunity: the role of environmental factors. Frontiers in bioscience (Elite edition). 2009; 1: 501-9.
[6]  Cerf-Bensussan N. Autoimmunity and diet. Nestle Nutr Workshop Ser Pediatr Program. 2009; 64: 91-9; discussion 9-104, 251-7.
[7]  Yang YH, Chiang BL. Novel approaches to food allergy. Clin Rev Allergy Immunol. 2014; 46: 250-7.
[8]  Rathe M, Muller K, Sangild PT, Husby S. Clinical applications of bovine colostrum therapy: a systematic review. Nutrition reviews. 2014; 72: 237-54.
[9]  Oftedal OT. The evolution of milk secretion and its ancient origins. Animal : an international journal of animal bioscience. 2012; 6: 355-68.
[10]  Hill DR, Newburg DS. Clinical applications of bioactive milk components. Nutrition reviews. 2015; 73: 463-76.
[11]  Kanwar JR, Kanwar RK, Sun X, Punj V, Matta H, Morley SM,et al. Molecular and biotechnological advances in milk proteins in relation to human health.
[12]  Curr Protein Pept Sci. 2009; 10: 308-38. Hernell O. Human milk vs. cow's milk and the evolution of infant formulas. Nestle Nutr Workshop Ser Pediatr Program. 2011; 67: 17-28.
[13]  Capuco AV, Akers RM. The origin and evolution of lactation. Journal of biology. 2009; 8: 37.
[14]  Haug A, Høstmark AT, Harstad OM. Bovine milk in human nutrition - a review. Lipids in Health and Disease. 2007; 6: 25-.
[15]  Heck JM, van Valenberg HJ, Dijkstra J, van Hooijdonk AC. Seasonal variation in the Dutch bovine raw milk composition. Journal of dairy science. 2009; 92: 4745-55.
[16]  Caroli AM, Chessa S, Erhardt GJ. Invited review: milk protein polymorphisms in cattle: effect on animal breeding and human nutrition. Journal of dairy science. 2009; 92: 5335-52.
[17]  Schwendel BH, Wester TJ, Morel PC, Tavendale MH, Deadman C, Shadbolt NM, et al. Invited review: organic and conventionally produced milk-an evaluation of factors influencing milk composition. Journal of dairy science. 2015; 98: 721-46.
[18]  Tao N, DePeters EJ, German JB, Grimm R, Lebrilla CB. Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. Journal of dairy science. 2009; 92: 2991-3001.
[19]  Thorsdottir I, Thorisdottir AV. Whole cow's milk in early life. Nestle Nutr Workshop Ser Pediatr Program. 2011; 67: 29-40.
[20]  Tannock GW, Lawley B, Munro K, Gowri Pathmanathan S, Zhou SJ, Makrides M, et al. Comparison of the Compositions of the Stool Microbiotas of Infants Fed Goat Milk Formula, Cow Milk-Based Formula, or Breast Milk. Applied and Environmental Microbiology. 2013; 79: 3040-8.
[21]  Martin CR, Ling PR, Blackburn GL. Review of Infant Feeding: Key Features of Breast Milk and Infant Formula. Nutrients. 2016; 8.
[22]  Amital H, Gershwin ME, Shoenfeld Y. Reshaping the mosaic of autoimmunity. Seminars in arthritis and rheumatism. 2006; 35: 341-3.
[23]  Munblit D, Peroni DG, Boix-Amoros A, Hsu PS, Land BV, Gay MCL, et al. Human Milk and Allergic Diseases: An Unsolved Puzzle. Nutrients. 2017; 9.
[24]  Perricone R, Perricone C, Shoenfeld Y. Autoimmunity: when the immune system becomes the self-ish giant. Autoimmun Rev. 2011; 10: 575-6.
[25]  Boyle RJ, Ierodiakonou D, Khan T, Chivinge J, Robinson Z, Geoghegan N, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. Bmj. 2016; 352: i974.
[26]  Okada H, Kuhn C, Feillet H, Bach JF. The 'hygiene hypothesis' for autoimmune and allergic diseases: an update. Clinical and experimental immunology. 2010; 160: 1-9.
[27]  McLean MH, Dieguez D, Jr., Miller LM, Young HA. Does the microbiota play a role in the pathogenesis of autoimmune diseases? Gut. 2015; 64: 332-41.
[28]  Schrezenmeir J, Jagla A. Milk and diabetes. J Am Coll Nutr. 2000; 19: 176s-90s.
[29]  Vaarala O, Hyoty H, Akerblom HK. Environmental factors in the aetiology of childhood diabetes. Diabetes, nutrition & metabolism. 1999; 12: 75-85.
[30]  Ahadi M, Tabatabaeiyan M, Moazzami K. Association between environmental factors and risk of type 1 diabetes - a case-control study. Endokrynologia Polska. 2011; 62: 134-7.
[31]  Antonela B, Ivana G, Ivan K, Nikolina V, Vesna BP, Marina P, et al. Environmental Risk Factors for Type 1 Diabetes Mellitus Development. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2017; 125: 563-70.
[32]  Villagran-Garcia EF, Hurtado-Lopez EF, Vasquez-Garibay EM, Troyo-Sanroman R, Aguirre-Salas LM, Larrosa-Haro A, et al. INTRODUCTION OF PASTEURIZED/RAW COW'S MILK DURING THE SECOND SEMESTER OF LIFE AS A RISK FACTOR OF TYPE 1 DIABETES MELLITUS IN SCHOOL CHILDREN AND ADOLESCENTS. Nutricion hospitalaria. 2015; 32: 634-7.
[33]  Lempainen J, Tauriainen S, Vaarala O, Makela M, Honkanen H, Marttila J, et al. Interaction of enterovirus infection and cow's milk-based formula nutrition in type 1 diabetes-associated autoimmunity. Diabetes Metab Res Rev. 2012; 28: 177-85.
[34]  Brown CT, Davis-Richardson AG, Giongo A, Gano KA, Crabb DB, Mukherjee N, et al. Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes. PloS one. 2011; 6: e25792.
[35]  Cerf-Bensussan N, Gaboriau-Routhiau V. The immune system and the gut microbiota: friends or foes? Nature reviews Immunology. 2010; 10: 735-44.
[36]  Hooper LV, Littman DR, Macpherson AJ. Interactions between the microbiota and the immune system. Science (New York, NY). 2012; 336: 1268-73.
[37]  de Goffau MC, Luopajarvi K, Knip M, Ilonen J, Ruohtula T, Harkonen T, et al. Fecal microbiota composition differs between children with beta-cell autoimmunity and those without. Diabetes. 2013; 62: 1238-44.
[38]  Lerner A, Aminov R, Matthias T. Dysbiosis May Trigger Autoimmune Diseases via Inappropriate Post-Translational Modification of Host Proteins. Front Microbiol. 2016; 7: 84.
[39]  Lerner A, Aminov R, Matthias T. Transglutaminases in Dysbiosis As Potential Environmental Drivers of Autoimmunity. Front Microbiol. 2017; 8: 66.
[40]  Maslowski KM, Mackay CR. Diet, gut microbiota and immune responses. Nature immunology. 2011; 12: 5-9.
[41]  Dahan S, Segal Y, Shoenfeld Y. Dietary factors in rheumatic autoimmune diseases: a recipe for therapy? Nature reviews Rheumatology. 2017; 13: 348-58.
[42]  Atkinson MA, Chervonsky A. Does the gut microbiota have a role in type 1 diabetes? Early evidence from humans and animal models of the disease. Diabetologia. 2012; 55: 2868-77.
[43]  Costello EK, Lauber CL, Hamady M, Fierer N, Gordon JI, Knight R. Bacterial community variation in human body habitats across space and time. Science (New York, NY). 2009; 326: 1694-7.
[44]  Endesfelder D, zu Castell W, Ardissone A, Davis-Richardson AG, Achenbach P, Hagen M, et al. Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes. 2014; 63: 2006-14.
[45]  Giongo A, Gano KA, Crabb DB, Mukherjee N, Novelo LL, Casella G, et al. Toward defining the autoimmune microbiome for type 1 diabetes. The ISME journal. 2011; 5: 82-91.
[46]  Endesfelder D, Engel M, Davis-Richardson AG, Ardissone AN, Achenbach P, Hummel S, et al. Towards a functional hypothesis relating anti-islet cell autoimmunity to the dietary impact on microbial communities and butyrate production. Microbiome. 2016; 4: 17.
[47]  Sechi LA, Paccagnini D, Salza S, Pacifico A, Ahmed N, Zanetti S. Mycobacterium avium subspecies paratuberculosis bacteremia in type 1 diabetes mellitus: an infectious trigger? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2008; 46: 148-9.
[48]  Masala S, Cossu D, Pacifico A, Molicotti P, Sechi LA. Sardinian Type 1 diabetes patients, Transthyretin and Mycobacterium avium subspecies paratuberculosis infection. Gut pathogens. 2012; 4: 24.
[49]  Niegowska M, Rapini N, Piccinini S, Mameli G, Caggiu E, Manca Bitti ML, et al. Type 1 Diabetes at-risk children highly recognize Mycobacterium avium subspecies paratuberculosis epitopes homologous to human Znt8 and Proinsulin. Scientific reports. 2016; 6: 22266.
[50]  Knip M, Virtanen SM, Seppa K, Ilonen J, Savilahti E, Vaarala O, et al. Dietary intervention in infancy and later signs of beta-cell autoimmunity. The New England journal of medicine. 2010; 363: 1900-8.
[51]  Garcia-Larsen V, Ierodiakonou D, Jarrold K, Cunha S, Chivinge J, Robinson Z, et al. Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis. PLoS Med. 2018; 15: e1002507.
[52]  Barker JM, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions. Advances in pediatrics. 2008; 55: 349-65.
[53]  Aaron Lerner PJ, Torsten Matthias. THE WORLD INCIDENCE OF CELIAC DISEASE IS INCREASING: A REVIEW. International Journal of Recent Scientific Research. 2015; 6: 5491-6.
[54]  Aaron Lerner PJ, Torsten Matthias. The World Incidence and Prevalence of Autoimmune Diseases is Increasing. International Journal of Celiac Disease. 2015; 3: 151-5.
[55]  Liu E, Lee HS, Aronsson CA, Hagopian WA, Koletzko S, Rewers MJ, et al. Risk of pediatric celiac disease according to HLA haplotype and country. The New England journal of medicine. 2014; 371: 42-9.
[56]  Catassi C, Gatti S, Fasano A. The new epidemiology of celiac disease. J Pediatr Gastroenterol Nutr. 2014; 59 Suppl 1: S7-9.
[57]  Szajewska H, Shamir R, Mearin L, Ribes-Koninckx C, Catassi C, Domellof M, et al. Gluten Introduction and the Risk of Coeliac Disease: A Position Paper by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2016; 62: 507-13.
[58]  Lionetti E, Castellaneta S, Francavilla R, Pulvirenti A, Tonutti E, Amarri S, et al. Introduction of gluten, HLA status, and the risk of celiac disease in children. The New England journal of medicine. 2014; 371: 1295-303.
[59]  Heyman M, Abed J, Lebreton C, Cerf-Bensussan N. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012; 61: 1355-64.
[60]  Lerner A, Matthias T. Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev. 2015; 14: 479-89.
[61]  Lerner A, Matthias T. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis. Nutr Rev. 2015; 73: 544-52.
[62]  Matthias T, Jeremias P, Neidhofer S, Lerner A. The industrial food additive, microbial transglutaminase, mimics tissue transglutaminase and is immunogenic in celiac disease patients. Autoimmun Rev. 2016; 15: 1111-9.
[63]  Lerner A, Shoenfeld Y, Matthias T. Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease. Nutr Rev. 2017; 75: 1046-58.
[64]  Lerner A, Ramesh A, Matthias T. Going gluten free in non-celiac autoimmune diseases: the missing ingredient. Expert Rev Clin Immunol. 2018; 14: 873-5.
[65]  Cabrera-Chavez F, de la Barca AM. Bovine milk intolerance in celiac disease is related to IgA reactivity to alpha- and beta-caseins. Nutrition (Burbank, Los Angeles County, Calif). 2009; 25: 715-6.
[66]  Dekking L, Koning F, Hosek D, Ondrak TD, Taylor SL, Schroeder JW, et al. Intolerance of celiac disease patients to bovine milk is not due to the presence of T-cell stimulatory epitopes of gluten. Nutrition (Burbank, Los Angeles County, Calif). 2009; 25: 122-3.
[67]  Hyytinen M, Savilahti E, Virtanen SM, Harkonen T, Ilonen J, Luopajarvi K, et al. Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial. Gastroenterology. 2017.
[68]  Hall EJ, Batt RM. Abnormal permeability precedes the development of a gluten sensitive enteropathy in Irish setter dogs. Gut. 1991; 32: 749-53.
[69]  Kristjansson G, Venge P, Hallgren R. Mucosal reactivity to cow's milk protein in coeliac disease. Clinical and experimental immunology. 2007; 147: 449-55.
[70]  Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A, et al. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005; 54: 1232-6.
[71]  Lidar M, Lipschitz N, Langevitz P, Barzilai O, Ram M, Porat-Katz BS, et al. Infectious serologies and autoantibodies in Wegener's granulomatosis and other vasculitides: novel associations disclosed using the Rad BioPlex 2200. Annals of the New York Academy of Sciences. 2009; 1173: 649-57.
[72]  Shor DB, Orbach H, Boaz M, Altman A, Anaya JM, Bizzaro N, et al. Gastrointestinal-associated autoantibodies in different autoimmune diseases. American journal of clinical and experimental immunology. 2012; 1: 49-55.
[73]  Rinaldi M, Perricone R, Blank M, Perricone C, Shoenfeld Y. Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity. Clin Rev Allergy Immunol. 2013; 45: 152-61.
[74]  A. Lerner MT. The Salutogenic Effects of Cow’s Milk and Dairy Products in Celiac Disease. Journal of Clinical & Cellular Immunology. 2018; 09.
[75]  Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflammatory bowel diseases. 2006; 12 Suppl 1: S3-9.
[76]  Zhang YZ, Li YY. Inflammatory bowel disease: pathogenesis. World J Gastroenterol. 2014; 20: 91-9.
[77]  Cassinotti A, Sarzi-Puttini P, Fichera M, Shoenfeld Y, de Franchis R, Ardizzone S. Immunity, autoimmunity and inflammatory bowel disease. Autoimmun Rev. 2014; 13: 1-2.
[78]  Glassman MS, Newman LJ, Berezin S, Gryboski JD. Cow's milk protein sensitivity during infancy in patients with inflammatory bowel disease. Am J Gastroenterol. 1990; 85: 838-40.
[79]  Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol. 2014; 133: 291-307; quiz 8.
[80]  Sicherer SH. Clinical aspects of gastrointestinal food allergy in childhood. Pediatrics. 2003; 111: 1609-16.
[81]  Imanzadeh F, Nasri P, Sadeghi S, Sayyari A, Dara N, Abdollah K, et al. Food allergy among Iranian children with inflammatory bowel disease: A preliminary report. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences. 2015; 20: 855-9.
[82]  Judaki A, Hafeziahmadi M, Yousefi A, Havasian MR, Panahi J, Sayehmiri K, et al. Evaluation of dairy allergy among ulcerative colitis patients. Bioinformation. 2014; 10: 693-6.
[83]  Virta LJ, Ashorn M, Kolho KL. Cow's milk allergy, asthma, and pediatric IBD. J Pediatr Gastroenterol Nutr. 2013; 56: 649-51.
[84]  Sechi LA, Gazouli M, Sieswerda LE, Molicotti P, Ahmed N, Ikonomopoulos J, et al. Relationship between Crohn's disease, infection with Mycobacterium avium subspecies paratuberculosis and SLC11A1 gene polymorphisms in Sardinian patients. World J Gastroenterol. 2006; 12: 7161-4.
[85]  McNees AL, Markesich D, Zayyani NR, Graham DY. Mycobacterium paratuberculosis as a cause of Crohn's disease. Expert review of gastroenterology & hepatology. 2015; 9: 1523-34.
[86]  Juste RA. Crohn's disease and ruminant farming. Got lactase? Med Hypotheses. 2010; 75: 7-13.
[87]  Ellingson JL, Anderson JL, Koziczkowski JJ, Radcliff RP, Sloan SJ, Allen SE, et al. Detection of viable Mycobacterium avium subsp. paratuberculosis in retail pasteurized whole milk by two culture methods and PCR. Journal of food protection. 2005; 68: 966-72.
[88]  Adhikari S, Caro Tohme T, Whiley H. Investigation of Mycobacterium avium complex (MAC) in Australian commercial milk using qPCR. The Journal of dairy research. 2017; 84: 89-91.
[89]  Lidar M, Langevitz P, Shoenfeld Y. The role of infection in inflammatory bowel disease: initiation, exacerbation and protection. The Israel Medical Association journal : IMAJ. 2009; 11: 558-63.
[90]  Thomas Dow C. Cows, Crohn's and more: is Mycobacterium paratuberculosis a superantigen? Med Hypotheses. 2008; 71: 858-61.
[91]  Lamb JR, Young DB. T cell recognition of stress proteins. A link between infectious and autoimmune disease. Molecular biology & medicine. 1990; 7: 311-21.
[92]  Jarjour WN, Jeffries BD, Davis JSt, Welch WJ, Mimura T, Winfield JB. Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases. Arthritis Rheum. 1991; 34: 1133-8.
[93]  Biet F, Gendt L, Anton E, Ballot E, Hugot JP, Johanet C. Serum antibodies to Mycobacterium avium subspecies paratuberculosis combined with anti-Saccharomyces cerevisiae antibodies in Crohn's disease patients: prevalence and diagnostic role. Digestive diseases and sciences. 2011; 56: 1794-800.
[94]  Lerner A, Park BH, Rossi TM, Lebenthal E. Increased serum antibody levels against cow's milk proteins in children with chronic liver disease. Hepatology. 1985; 5: 488-91.
[95]  Anaya JM, Shoenfeld Y, Buttgereit F, Gonzalez-Gay MA. Autoimmune rheumatic diseases. BioMed research international. 2014; 2014: 952159.
[96]  Shor DB, Shoenfeld Y. Autoimmunity: Will worms cure rheumatoid arthritis? Nature reviews Rheumatology. 2013; 9: 138-40.
[97]  Bragazzi NL, Watad A, Neumann SG, Simon M, Brown SB, Abu Much A, et al. Vitamin D and rheumatoid arthritis: an ongoing mystery. Current opinion in rheumatology. 2017; 29: 378-88.
[98]  Kaufman W. Food-induced, allergic musculoskeletal syndromes. Annals of allergy. 1953; 11: 179-84.
[99]  van de Putte LB, Lens JW, van den Berg WB, Kruijsen MW. Exacerbation of antigen-induced arthritis after challenge with intravenous antigen. Immunology. 1983; 49: 161-7.
[100]  Hanglow AC, Welsh CJ, Conn P, Coombs RR. Early rheumatoid-like synovial lesions in rabbits drinking cow's milk. II. Antibody responses to bovine serum proteins. International archives of allergy and applied immunology. 1985; 78: 152-60.
[101]  Perez-Maceda B, Lopez-Bote JP, Langa C, Bernabeu C. Antibodies to dietary antigens in rheumatoid arthritis--possible molecular mimicry mechanism. Clinica chimica acta; international journal of clinical chemistry. 1991; 203: 153-65.
[102]  Mowat AM. The regulation of immune responses to dietary protein antigens. Immunology today. 1987; 8: 93-8.
[103]  Hvatum M, Kanerud L, Hallgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut. 2006; 55: 1240-7.
[104]  Li J, Yan H, Chen H, Ji Q, Huang S, Yang P, et al. The Pathogenesis of Rheumatoid Arthritis is Associated with Milk or Egg Allergy. North American Journal of Medical Sciences. 2016; 8: 40-6.
[105]  Maddaloni M, Kochetkova I, Jun S, Callis G, Thornburg T, Pascual DW. Milk-based nutraceutical for treating autoimmune arthritis via the stimulation of IL-10- and TGF-beta-producing CD39+ regulatory T cells. PloS one. 2015; 10: e0117825.
[106]  Arntz OJ, Pieters BC, Oliveira MC, Broeren MG, Bennink MB, de Vries M, et al. Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models. Molecular nutrition & food research. 2015; 59: 1701-12.
[107]  Arab HH, Salama SA, Abdelghany TM, Omar HA, Arafa EA, Alrobaian MM, et al. Camel Milk Attenuates Rheumatoid Arthritis Via Inhibition of Mitogen Activated Protein Kinase Pathway. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017; 43: 540-52.
[108]  Lerner A, Matthias T. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. Autoimmun Rev. 2015; 14: 1038-47.
[109]  Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet (London, England). 2011; 377: 2138-49.
[110]  Ellis JA, Munro JE, Ponsonby AL. Possible environmental determinants of juvenile idiopathic arthritis. Rheumatology (Oxford). 2010; 49: 411-25.
[111]  Shapira Y, Agmon-Levin N, Shoenfeld Y. Geoepidemiology of autoimmune rheumatic diseases. Nature reviews Rheumatology. 2010; 6: 468-76.
[112]  Arvonen M, Virta LJ, Pokka T, Kroger L, Vahasalo P. Cow's Milk Allergy in Infancy and Later Development of Juvenile Idiopathic Arthritis: A Register-Based Case-Control Study. American journal of epidemiology. 2017; 186: 237-44.
[113]  Arvonen M, Ikni L, Augustin M, Karttunen TJ, Vahasalo P. Increase of duodenal and ileal mucosal cytotoxic lymphocytes in juvenile idiopathic arthritis. Clinical and experimental rheumatology. 2010; 28: 128-34.
[114]  Pichler J, Ong C, Shah N, Sebire N, Kiparrissi F, Borrelli O, et al. Histopathological features of gastrointestinal mucosal biopsies in children with juvenile idiopathic arthritis. Pediatr Res. 2016; 79: 895-901.
[115]  Metsala J, Lundqvist A, Virta LJ, Kaila M, Gissler M, Virtanen SM. Mother's and offspring's use of antibiotics and infant allergy to cow's milk. Epidemiology (Cambridge, Mass). 2013; 24: 303-9.
[116]  Arvonen M, Virta LJ, Pokka T, Kroger L, Vahasalo P. Repeated exposure to antibiotics in infancy: a predisposing factor for juvenile idiopathic arthritis or a sign of this group's greater susceptibility to infections? J Rheumatol. 2015; 42: 521-6.
[117]  Golding DN. Is there an allergic synovitis? Journal of the Royal Society of Medicine. 1990; 83: 312-4.
[118]  Kindgren E, Fredrikson M, Ludvigsson J. Early feeding and risk of Juvenile idiopathic arthritis: a case control study in a prospective birth cohort. Pediatr Rheumatol Online J. 2017; 15: 46.
[119]  Schrander JJ, Marcelis C, de Vries MP, van Santen-Hoeufft HM. Does food intolerance play a role in juvenile chronic arthritis? British journal of rheumatology. 1997; 36: 905-8.
[120]  Ratner D, Eshel E, Vigder K. Juvenile rheumatoid arthritis and milk allergy. Journal of the Royal Society of Medicine. 1985; 78: 410-3.
[121]  Beck LH, Jr., Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. The New England journal of medicine. 2009; 361: 11-21.
[122]  Debiec H, Lefeu F, Kemper MJ, Niaudet P, Deschenes G, Remuzzi G, et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin. The New England journal of medicine. 2011; 364: 2101-10.
[123]  Mogues T, Li J, Coburn J, Kuter DJ. IgG antibodies against bovine serum albumin in humans--their prevalence and response to exposure to bovine serum albumin. Journal of immunological methods. 2005; 300: 1-11.
[124]  Fogo AB. Milk and membranous nephropathy. The New England journal of medicine. 2011; 364: 2158-9.
[125]  Ireland R. Glomerular disease: Bovine serum albumin: involved in childhood membranous nephropathy? Nature reviews Nephrology. 2011; 7: 423.
[126]  Beck LH, Jr. Childhood membranous nephropathy and dietary antigens. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2012; 59: 174-6.
[127]  Soylu A, Kasap B, Soylu OB, Turkmen M, Kavukcu S. Does feeding in infancy effect the development of IgA nephropathy? Pediatr Nephrol. 2007; 22: 1040-4.
[128]  de Carvalho JF, Pereira RM, Shoenfeld Y. Pearls in autoimmunity. Auto- immunity highlights. 2011; 2: 1-4.
[129]  Butcher PJ. Milk consumption and multiple sclerosis--an etiological hypothesis. Med Hypotheses. 1986; 19: 169-78.
[130]  Malosse D, Perron H, Sasco A, Seigneurin JM. Correlation between milk and dairy product consumption and multiple sclerosis prevalence: a worldwide study. Neuroepidemiology. 1992; 11: 304-12.
[131]  Lauer K. Diet and multiple sclerosis. Neurology. 1997; 49: S55-61.
[132]  Shor DB, Barzilai O, Ram M, Izhaky D, Porat-Katz BS, Chapman J, et al. Gluten sensitivity in multiple sclerosis: experimental myth or clinical truth? Annals of the New York Academy of Sciences. 2009; 1173: 343-9.
[133]  Stefferl A, Schubart A, Storch M, Amini A, Mather I, Lassmann H, et al. Butyrophilin, a milk protein, modulates the encephalitogenic T cell response to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis. Journal of immunology (Baltimore, Md : 1950). 2000; 165: 2859-65.
[134]  Winer S, Astsaturov I, Cheung RK, Schrade K, Gunaratnam L, Wood DD, et al. T cells of multiple sclerosis patients target a common environmental peptide that causes encephalitis in mice. Journal of immunology (Baltimore, Md : 1950). 2001; 166: 4751-6.
[135]  Guggenmos J, Schubart AS, Ogg S, Andersson M, Olsson T, Mather IH, et al. Antibody cross-reactivity between myelin oligodendrocyte glycoprotein and the milk protein butyrophilin in multiple sclerosis. Journal of immunology (Baltimore, Md : 1950). 2004; 172: 661-8.
[136]  Otaegui D, Mostafavi S, Bernard CCA, de Munain AL, Mousavi P, Oksenberg JR, et al. Increased Transcriptional Activity of Milk-Related Genes following the Active Phase of Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis. The Journal of Immunology. 2007; 179: 4074.
[137]  Mokarizadeh A, Hassanzadeh K, Abdi M, Soraya H, Faryabi MR, Mohammadi E, et al. Transdermal delivery of bovine milk vesicles in patients with multiple sclerosis: A novel strategy to induce MOG-specific tolerance. Med Hypotheses. 2015; 85: 141-4.
[138]  Watad A, Tiosano S, Yahav D, Comaneshter D, Shoenfeld Y, Cohen AD, et al. Behcet's disease and familial Mediterranean fever: Two sides of the same coin or just an association? A cross-sectional study. European journal of internal medicine. 2017; 39: 75-8.
[139]  Triolo G, Accardo-Palumbo A, Dieli F, Ciccia F, Ferrante A, Giardina E, et al. Humoral and cell mediated immune response to cow's milk proteins in Behcet's disease. Ann Rheum Dis. 2002; 61: 459-62.
[140]  Eisenstein TK. Opioids and the immune system: what is their mechanism of action? British journal of pharmacology. 2011; 164: 1826-8.
[141]  Roy S, Loh HH. Effects of opioids on the immune system. Neurochemical research. 1996; 21: 1375-86.
[142]  Lehner T. The role of heat shock protein, microbial and autoimmune agents in the aetiology of Behcet's disease. International reviews of immunology. 1997; 14: 21-32.
[143]  Gershwin ME, Shoenfeld Y. Cutting-edge issues in organ-specific autoimmunity. Clin Rev Allergy Immunol. 2011; 41: 123-5.
[144]  Lee RW, Nicholson LB, Sen HN, Chan CC, Wei L, Nussenblatt RB, et al. Autoimmune and autoinflammatory mechanisms in uveitis. Seminars in immunopathology. 2014; 36: 581-94.
[145]  Pras E, Neumann R, Zandman-Goddard G, Levy Y, Assia EI, Shoenfeld Y, et al. Intraocular inflammation in autoimmune diseases. Seminars in arthritis and rheumatism. 2004; 34: 602-9.
[146]  Wildner G, Diedrichs-Mohring M. Autoimmune uveitis and antigenic mimicry of environmental antigens. Autoimmun Rev. 2004; 3: 383-7.
[147]  Wildner G, Diedrichs-Mohring M. Autoimmune uveitis induced by molecular mimicry of peptides from rotavirus, bovine casein and retinal S-antigen. European journal of immunology. 2003; 33: 2577-87.
[148]  Krause I, Blank M, Shoenfeld Y. New treatment avenues: oral tolerance--mechanisms and applicability to human diseases. The Israel Medical Association journal : IMAJ. 1999; 1: 45-9.
[149]  Tsirouki T, Dastiridou A, Symeonidis C, Tounakaki O, Brazitikou I, Kalogeropoulos C, et al. A Focus on the Epidemiology of Uveitis. Ocular immunology and inflammation. 2016: 1-15.
[150]  Gilat Y, Shoenfeld Y, Kotler M, Iancu I. Anti-ribosomal P antibody in schizophrenia. The Israel journal of psychiatry and related sciences. 2011; 48: 275-9.
[151]  Dohan FC. Genetic hypothesis of idiopathic schizophrenia: its exorphin connection. Schizophr Bull. 1988; 14: 489-94.
[152]  Drysdale A, Deacon R, Lewis P, Olley J, Electricwala A, Sherwood R. A peptide-containing fraction of plasma from schizophrenic patients which binds to opiate receptors and induces hyper-reactivity in rats. Neuroscience. 1982; 7: 1567-73.
[153]  Reichelt KL, Hole K, Hamberger A, Saelid G, Edminson PD, Braestrup CB, et al. Biologically active peptide-containing fractions in schizophrenia and childhood autism. Advances in biochemical psychopharmacology. 1981; 28: 627-43.
[154]  Lindstrom LH, Besev G, Gunne LM, Terenius L. CSF levels of receptor-active endorphins in schizophrenic patients: correlations with symptomatology and monoamine metabolites. Psychiatry research. 1986; 19: 93-100.
[155]  Reichelt KL, Stensrud M. Increase in urinary peptides prior to the diagnosis of schizophrenia. Schizophrenia research. 1998; 34: 211-3.
[156]  Severance EG, Gressitt KL, Alaedini A, Rohleder C, Enning F, Bumb JM, et al. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia. Brain, behavior, and immunity. 2015; 44: 148-58.
[157]  Reichelt KL, Seim AR, Reichelt WH. Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload? Progress in neuro-psychopharmacology & biological psychiatry. 1996; 20: 1083-114.
[158]  Severance EG, Dickerson FB, Halling M, Krivogorsky B, Haile L, Yang S, et al. Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onset psychosis and schizophrenia. Schizophrenia research. 2010; 118: 240-7.
[159]  Severance EG, Lin J, Sampson HA, Gimenez G, Dickerson FB, Halling M, et al. Dietary antigens, epitope recognition, and immune complex formation in recent onset psychosis and long-term schizophrenia. Schizophrenia research. 2011; 126: 43-50.
[160]  Severance EG, Gressitt KL, Halling M, Stallings CR, Origoni AE, Vaughan C, et al. Complement C1q formation of immune complexes with milk caseins and wheat glutens in schizophrenia. Neurobiology of disease. 2012; 48: 447-53.
[161]  Severance EG, Gressitt KL, Yang S, Stallings CR, Origoni AE, Vaughan C, et al. Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Bipolar disorders. 2014; 16: 230-40.
[162]  Niebuhr DW, Li Y, Cowan DN, Weber NS, Fisher JA, Ford GM, et al. Association between bovine casein antibody and new onset schizophrenia among US military personnel. Schizophrenia research. 2011; 128: 51-5.
[163]  Jirillo F, Jirillo E, Magrone T. Donkey's and goat's milk consumption and benefits to human health with special reference to the inflammatory status. Current pharmaceutical design. 2010; 16: 859-63.
[164]  Monti G, Bertino E, Muratore MC, Coscia A, Cresi F, Silvestro L, et al. Efficacy of donkey's milk in treating highly problematic cow's milk allergic children: an in vivo and in vitro study. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2007; 18: 258-64.
[165]  Jirillo F, Magrone T. Anti-inflammatory and anti-allergic properties of donkey's and goat's milk. Endocrine, metabolic & immune disorders drug targets. 2014; 14: 27-37.
[166]  Sayed LH, Badr G, Omar HM, Abd El-Rahim AM, Mahmoud MH. Camel whey protein improves oxidative stress and histopathological alterations in lymphoid organs through Bcl-XL/Bax expression in a streptozotocin-induced type 1 diabetic mouse model. Biomed Pharmacother. 2017; 88: 542-52.
[167]  Badr G, Mohany M, Metwalli A. Effects of undenatured whey protein supplementation on CXCL12- and CCL21-mediated B and T cell chemotaxis in diabetic mice. Lipids Health Dis. 2011; 10: 203.
[168]  Badr G, Sayed LH, Omar HEM, Abd El-Rahim AM, Ahmed EA, Mahmoud MH. Camel Whey Protein Protects B and T Cells from Apoptosis by Suppressing Activating Transcription Factor-3 (ATF-3)-Mediated Oxidative Stress and Enhancing Phosphorylation of AKT and IkappaB-alpha in Type I Diabetic Mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2017; 41: 41-54.
[169]  Al-Ayadhi LY, Halepoto DM, Al-Dress AM, Mitwali Y, Zainah R. Behavioral Benefits of Camel Milk in Subjects with Autism Spectrum Disorder. J Coll Physicians Surg Pak. 2015; 25: 819-23.
[170]  Karkee R, Lee AH, Khanal V, Binns CW. Infant feeding information, attitudes and practices: a longitudinal survey in central Nepal. International breastfeeding journal. 2014; 9: 14.
[171]  Hurley WL, Theil PK. Perspectives on immunoglobulins in colostrum and milk. Nutrients. 2011; 3: 442-74.
[172]  Boldogh I, Aguilera-Aguirre L, Bacsi A, Choudhury BK, Saavedra-Molina A, Kruzel M. Colostrinin decreases hypersensitivity and allergic responses to common allergens. Int Arch Allergy Immunol. 2008; 146: 298-306.
[173]  Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr. 2000; 84 Suppl 1: S3-10.