International Journal of Celiac Disease
ISSN (Print): 2334-3427 ISSN (Online): 2334-3486 Website: Editor-in-chief: Samasca Gabriel
Open Access
Journal Browser
International Journal of Celiac Disease. 2019, 7(1), 21-25
DOI: 10.12691/ijcd-7-1-7
Open AccessArticle

The Gut Feeling of the Joints: Celiac Disease and Rheumatoid Arthritis Are Related

Lerner Aaron1, , Wusterhausen Patricia1, Ramesh Ajay1, Lopez Francois1 and Matthias Torsten1

1AESKU.KIPP Institute, Wendelsheim, Germany

Pub. Date: March 10, 2019

Cite this paper:
Lerner Aaron, Wusterhausen Patricia, Ramesh Ajay, Lopez Francois and Matthias Torsten. The Gut Feeling of the Joints: Celiac Disease and Rheumatoid Arthritis Are Related. International Journal of Celiac Disease. 2019; 7(1):21-25. doi: 10.12691/ijcd-7-1-7


The “mosaic of autoimmunity” is a complex, multiple-faceted, challenging scientific enigma. Celiac disease and rheumatoid arthritis are part of the autoimmune bee hive and despite being separate entities, they share multiple aspects. The present review summarizes the epidemiological, clinical, serological, genetic, environmental, enteric eco-events and associated diseases shared by the two mechanistically similar though different antigenic entities.

celiac disease rheumatoid arthritis HLA microbiome/dysbiome leaky gut post translational modification of proteins

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing: A review. Internat J Celiac Disease. 2015; 3: 151-155.
[2]  Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med. 2002; 347: 911-920.
[3]  Lerner A, Jeremias P, Matthias T. The world incidence of celiac disease is increasing: a review. Internat. J. Of Recent Scient. Res. 2015; 7: 5491-5496.
[4]  Lerner A, Matthias T. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. Autoimm Rev. 2015: 14: 1038-1047.
[5]  Lerner A, Neidhöfer S, Matthias T. Beyond the joint: what’s happening in the gut. Internat J Celiac Dis. 2016; 4: 127-129.
[6]  Perricone C, Agmon-Levin N, Shoenfeld Y. Novel pebbles in the mosaic of autoimmunity. BMC Med. 2013; 11: 101.
[7]  Samasca G, Ramesh A, Sur D, Cornel A, Sur L, Floca E, et al. Polyautoimmunity - The missing ingredient. Autoimmun Rev. 2018; 17: 840-841.
[8]  Mounir A, Akasbi N, Siar N, harzy T. Coeliac disease with rheumatoid arthritis: An Unusual Association. Internat. J Celiac Dis. 2019; 7: DOI: 10.12691/ijcd-7-1-1.
[9]  Lerner A, Lopez F, Schmiedl A, Matthias T. The Underdiagnosed Enemy: Africa Goes Celiac? Internat. J Celiac Dis. 2019; 7: DOI: 10.12691/ijcd-7-1-3.
[10]  Lerner A, Arleevskaya M, Schmiedl A, Matthias T. Microbes and viruses are bugging the gut in celiac disease. Are they friends or foes? Frontiers in Microbiol. 2017; 8: 1392.
[11]  Lerner A, Shamir R. Influences of environment and knowledge on celiac disease – new perspectives. Harefuah 2002; 141; 46-47.
[12]  Lerner A, Matthias T. Gluten and autoimmunogenesis. I; Musaic of Autoimmunity, The novel factors of autoimmune diseases revisited. 2nd edition, Eds: Shoenfield Y, Perricone C. Pub: Elsevier. 2019. pp: 315-321
[13]  Lerner A. Reif S. Celiac and infection. In: Infections and Autoimmunity. Eds: Shoenfeld Y and Rose N. Elsevier B.V. Amsterdam, p.689 – 692. 2004.
[14]  Lerner A, Reif S. Nonnutritional environmental factors associated with Celiac disease: The Infectome . In: Infections and Autoimmunity. Eds: Shoenfeld Y, Agmon-Levine N, Rose NR. 2nd Ed. Elsevier B.V. Amsterdam, Chapter 50. 2015, pages 829-837.
[15]  Iqbal T, Zaidi MA, Wells GA, Karsh J. Celiac disease arthropathy and autoimmunity study. J Gastroenterol Hepatol. 2013; 28: 99-105.
[16]  Lubrano E, Ciacci C, Ames PR, Mazzacca G, Oriente P, Scarpa R. The arthritis of coeliac disease: prevalence and pattern in 200 adult patients. Br J Rheumatol. 1996; 35: 1314-1318.
[17]  Ghozzi M, Sakly W, Mankaï A, Bouajina E, Bahri F, Nouira R, et al. Screening for celiac disease, by endomysial antibodies, in patients with unexplained articular manifestations. Rheumatol Int. 2014; 34: 637-642.
[18]  Iagnocco A, Ceccarelli F, Mennini M, Rutigliano IM, Perricone C, Nenna R, et al. Subclinical synovitis detected by ultrasound in children affected by coeliac disease: a frequent manifestation improved by a gluten-free diet. Clin Exp Rheumatol. 2014; 32: 137-142.
[19]  Lerner A, Shoenfeld Y, Matthias T. Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease. Nutr Rev. 2017; 75: 1046-1058.
[20]  Fayyaz B, Gunawan F, Rehman HJ. ‘Preclinical’ rheumatoid arthritis in patients with celiac disease: A cross-sectional study. J Community Hosp Internal Med Perspectives. 2019.
[21]  Ebert EC, Hagspiel KD. Gastrointestinal and hepatic manifestations of rheumatoid arthritis. Dig Dis Sci. 2011; 56: 295-302.
[22]  Pak S, Darr U, Khan Z, Kobalka A, Safadi Z, Dee C. Concurrent Occurrence of Primary Biliary Cirrhosis and Rheumatoid Arthritis. Cureus. 2017; 9: e1562.
[23]  Smyk DS, Bogdanos DP, Mytilinaiou MG, Burroughs AK, Rigopoulou EI. Rheumatoid arthritis and primary biliary cirrhosis: cause, consequence, or coincidence?. 2012; 2012: 391567.
[24]  Lerner A, Ramesh A, Matthias T. Are Non-Celiac Autoimmune Diseases Responsive to Gluten-Free Diet? Internat J Celiac Disease 2017; 5: 164-167.
[25]  Lerner A, Ramesh A, Matthias T. Going gluten free in non- celiac autoimmune diseases: The missing ingredient. Expert Rev Clin Immunol. 2018 Sep 15: 1-3.
[26]  Badsha H. Role of Diet in Influencing Rheumatoid Arthritis Disease Activity. Open Rheumatol J. 2018; 12: 19-28.
[27]  El-Chammas K, Danner E. Gluten-free diet in nonceliac disease. Nutr Clin Pract. 2011; 26: 294-299.
[28]  Lauret E, Rodrigo L. Celiac disease and autoimmune-associated conditions. Biomed Res Int. 2013; 2013: 127589.
[29]  Lerner A, Blank M, Lahat N, Shoenfeld Y. Increased prevalence of autoantibodies in celiac disease. Dig Dis Sci. 1998; 43: 723-726.
[30]  Shaoul R, Lerner A. Associated autoantibodies in celiac disease. Autoimmun Rev. 2007; 6: 559-565.
[31]  Shor DB, Orbach H, Boaz M, Altman A, Anaya JM, Bizzaro N, et al. Gastrointestinal-associated autoantibodies in different autoimmune diseases. Am J Clin Exp Immunol. 2012; 1: 49-55.
[32]  Elhami E, Zakeri Z, Sadeghi A, Rostami-Nejad M, Volta U, Zali MR. nPrevalence of celiac disease in Iranian patients with rheumatologic disorders. Gastroenterol Hepatol Bed Bench. 2018; 11: 239-243.
[33]  Caio G, De Giorgio R, Ursini F, Fanaro S, Volta U. Prevalence of celiac disease serological markers in a cohort of Italian rheumatological patients. Gastroenterol Hepatol Bed Bench. 2018; 11: 244-249.
[34]  Bodis G, Toth V, Schwarting A. Role of Human Leukocyte Antigens (HLA) in Autoimmune Diseases. Rheumatol Ther. 2018; 5: 5-20.
[35]  Koning F. Recent insight in the pathophysiology of coeliac disease: relevance to rheumatoid arthritis. Clin Exp Rheumatol. 2015; 33(4 Suppl 92): S8-10.
[36]  Gutierrez-Achury J, Zorro MM, Ricaño-Ponce I, Zhernakova DV; Coeliac Disease Immunochip Consortium, RACI Consortium, Diogo D, et al. Functional implications of disease-specific variants in loci jointly associated with coeliac disease and rheumatoid arthritis. Hum Mol Genet. 2016; 25: 180-90.
[37]  Márquez A, Kerick M, Zhernakova A, Gutierrez-Achury J, Chen WM, Onengut-Gumuscu S, et al. Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations. Genome Med. 2018; 10: 97.
[38]  Koning F, Thomas R, Rossjohn J, Toes RE. Coeliac disease and rheumatoid arthritis: similar mechanisms, different antigens. Nat Rev Rheumatol. 2015; 11: 450-61.
[39]  Trollmo C, Sollerman C, Carlsten H, Tarkowski A.The gut as an inductive site for synovial and extra-articular immune responses in rheumatoid arthritis. Ann Rheum Dis. 1994; 53: 377-382.
[40]  Phillips R. Rheumatoid arthritis: Microbiome reflects status of RA and response to therapy. Nat Rev Rheumatol. 2015; 11: 502.
[41]  Podas T, Nightingale JM, Oldham R, Roy S, Sheehan NJ, Mayberry JF. Is rheumatoid arthritis a disease that starts in the intestine? A pilot study comparing an elemental diet with oral prednisolone. Postgrad Med J. 2007; 83: 128-131.
[42]  Lerner A, Matthias T. GUT-the Trojan horse in remote organs’ autoimmunity. Journal of Clinical & Cellular Immunology, 2016; 7: 401.
[43]  Lerner A, Aminov R, Matthias T. Dysbiosis may trigger autoimmune diseases via inappropriate posttranslational modification of host proteins. Frontiers in Microbiology. 2016; 7: Article 84.
[44]  Lerner A, Aminov R, Matthias T. Intestinal dysbiotic transglutaminases are potential environmental drivers of systemic autoimmunogenesis. Frontiers in Microbiology, 2017; 8; article 66.
[45]  Lerner A, Aminov R, Matthias T. Potential effects of horizontal gene exchange in the human gut. Front Immunol. 2017; 8: 1630.
[46]  Lerner A, Neidhöfer S, Matthias T. The gut microbiome feelings of the brain: perspective for Non-Microbiologists. Microorganisms. 2017; 5(4): 66.
[47]  Guerreiro CS, Calado Â, Sousa J, Fonseca JE. Diet, Microbiota, and Gut Permeability-The Unknown Triad in Rheumatoid Arthritis. Front Med (Lausanne). 2018; 5: 349.
[48]  De Filippis F, Pasolli E, Tett A, Tarallo S, Naccarati A, De Angelis M, et al. Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets. Cell Host Microbe. 2019; 25: 444-453.e3.
[49]  Girbovan A, Sur G, Samasca G, Lupan I. Dysbiosis a risk factor for celiac disease. Med Microbiol Immunol. 2017; 206: 83-91.
[50]  Krishnareddy S. The Microbiome in Celiac Disease. Gastroenterol Clin North Am. 2019; 48: 115-126.
[51]  Lerner A, Neidhöfer S, Matthias T. Serological markers and/or intestinal biopsies in the case-finding of celiac disease. Editorial, Internat. J Celiac dis. 2015; 3: 53-55.
[52]  Lerner A, Jeremias P, Neidhöfer S, Matthias T. Antibodies against neo-epitope tTg complexed to gliadin are different and more reliable then anti-tTg for the diagnosis of pediatric celiac disease. J Immunol Methods. 2016; 429: 15-20.
[53]  Lerner A. Serological Diagnosis of Celiac Disease –Moving Beyond the Tip of the Iceberg. International Journal of Celiac Disease. 2014; 2: 64-66.
[54]  Lerner A, Matthias T. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis. Nutr Rev. 2015; 73: 544-552.
[55]  Matthias T, Jeremias P, Neidhöfer S, Lerner A. The industrial food additive microbial transglutaminase, mimics the tissue transglutaminase and is immunogenic in celiac disease patients. Autoimmun Rev, 2016; 15: 1111-1119.
[56]  Matthias T, Lerner A. Microbial transglutaminase is immunogenic and potentially pathogenic in pediatric celiac disease. Front. In Pediatr. 2018; 6: 389.
[57]  Lerner A, Matthias T. Microbial transglutaminase: a new potential player in celiac disease. Clin Immunol. 2019; 199: 37-43. pii: S1521-6616(18)30717-4.
[58]  Lerner A, Matthias T. Microbial Transglutaminase is Beneficial to Food Industries but a Caveat to Public Health. Med One. 2019; 4: e190001.
[59]  Żylińska B, Silmanowicz P, Sobczyńska-Rak A, Jarosz Ł, Szponder T. Treatment of Articular Cartilage Defects: Focus on Tissue Engineering. In Vivo. 2018; 32: 1289-1300.
[60]  Madry H, Orth P, Cucchiarini M. Gene Therapy for Cartilage Repair. Cartilage. 2011; 2: 201-25.
[61]  Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012; 42: 71-8.
[62]  Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016; 4: e1251384.
[63]  Ajamian M, Steer D, Rosella G, Gibson PR. Serum zonulin as a marker of intestinal mucosal barrier function: May not be what it seems. PLoS One. 2019; 14: e0210728.
[64]  Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015; 7: 1565-1576.
[65]  Gurol G, Ciftci IH, Harman H, Karakece E, Kamanli A, Tekeoglu I. Roles of claudin-5 and von Willebrand factor in patients with rheumatoid arthritis. Int J Clin Exp Pathol. 2015; 8: 1979-1984.
[66]  Lerner A, Matthias T. Extraintestinal manifestations of CD: Common pathways in the gut-remote organs’ axes. Internat J Celiac Dis. 2017; 5: 24-27.
[67]  Lerner A, Matthias T, Wusterhausen P. Autoimmunity in celiac disease: extra-intestinal manifestations. Autoimm. Rev. 2019; 18: 241-246.
[68]  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: 479-489.
[69]  Hafstrom I, Ringertz B, Spangberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001; 40: 1175-1179.
[70]  Elkan AC, Sjoberg B, Kolsrud B, et al. Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Res Ther. 2008; 10: R34-R41.