Beyond the Joint: What’s Happening in the Gut

Aaron Lerner^{1, 2,} , Sandra Neidhöfer² and Torsten Matthias²

¹B. Rappaport School of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

²AESKU.KIPP Institute, Wendelsheim, Germany

Cite this paper:
Aaron Lerner, Sandra Neidhöfer and Torsten Matthias. Beyond the Joint: What’s Happening in the Gut. International Journal of Celiac Disease. 2016; 4(4):127-129. doi: 10.12691/ijcd-4-4-1

Abstract

Rheumatoid arthritis and celiac disease belong to the autoimmune disease family. Despite being separate entities they share multiple serological and genetic aspects. Celiac disease associated serum bio-markers are observed in rheumatoid arthritis. Contrary to their specific HLA pre-disposition, the diseases share multiple non-HLA loci. Those genes are crucial for activation and regulation of adaptive and innate immunity. Recently, light was shed on the interaction between host genetics and microbiota composition in relation to celiac disease and rheumatoid arthritis susceptibility, connecting bugs and us and autoimmunity. The present editorial updates and clarifies those aspects.

Keywords:
celiac disease rheumatoid arthritis serology genetics gut-joint axis bio-marker

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Sur LM, Floca E, Sur G, Rednic S. Serological and Genetic Evidence of Celiac Disease in Juvenile Arthritis and Rheumatoid Arthritis. Internat J of Celiac Dis 2016; 4: 82-83.
[2]	Lerner A, Matthias T. GUT-the Trojan horse in remote organs’ autoimmunity. J Clin Cell Immunol 2016; 7: 401.
[3]	Lerner A, Neidhöfer S, Matthias T. Transglutaminase 2 and anti transglutaminase 2 autoantibodies in celiac disease and beyond. Part B: Anti- Transglutaminase 2 autoantibodies: friends or enemies. Immunome Research 2015; 11: 3-7.
[4]	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.
[5]	Koehne Vde B, Bahia M, Lanna CC, Pinto MR, Bambirra EA, Cunha AS. Prevalence of serological markers for celiac disease (IgA and IgG class antigliadin antibodies and IgA class antiendomysium antibodies) in patients with autoimmune rheumatologic diseases in Belo Horizonte, MG, Brazil. Arq Gastroenterol 2010; 47: 250-256.
[6]	Skare T, Nisihara RM, Utiyama SR. Is it worth investigating coeliac disease in patients with rheumatic disorders? Rheumatology (Oxford) 2013; 52: 217-218.
[7]	Tucker NT, Barghuthy FS, Prihoda TJ, Kumar V, Lerner A, Lebenthal E. Antigliadin antibodies detected by enzyme linked immunosorbent assay (ELISA) as a marker of childhood celiac disease. J Pediatr 1988; 113: 286-289.
[8]	Lerner A, Kumar V, Iancu TC. Immunological diagnosis of childhood celiac disease: comparison between antigliadin, antireticulin and antiendomysial antibodies. Clin Exper Immunol 1994; 95: 78-82.
[9]	Roth EB, Stenberg P, Book C, Sjöberg K. Antibodies against transglutaminases, peptidylarginine deiminase and citrulline in rheumatoid arthritis—new pathways to epitope spreading. Clin Exp Rheumatol 2006; 24: 12-18.
[10]	Stoll ML, Pate AS, Christadoss ML, Punaro M, Olsen NJ. IgA transglutaminase levels in childrenwith Juvenile Idiopathic arthritis. Ann Paediatr Rheumatol 2012; 1: 31-35.
[11]	Song KS, Choi JR. Tissue transglutaminase autoantibodies in patients with IgM rheumatoid factors. Yonsei Med J 2004; 45: 960-962.
[12]	Hällgren J, Knutson F, Lavö B, Hällgren R. Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease. Clin Exp Immunol 1996; 103: 94-98.
[13]	Feighery L, Collins C, Feighery C, Mahmud N, Coughlan G, Willoughby R, et al. Anti-transglutaminase antibodies and the serological diagnosis of coeliac disease. Br J Biomed Sci 2003; 60: 14-18.
[14]	Liao KP, Kurreeman F, Li G, Duclos G. Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls. Arthritis Rheum 2013; 65: 571-581.
[15]	Spadaro A, Sorgi ML, Scrivo R, Picarelli A, Tola MD, Sabbatella L, Taccari E. [Anti-tissue transglutaminase antibodies in inflammatory and degenerative arthropathies].[Article in Italian]. Reumatismo 2002; 54: 344-350.
[16]	Gheita TA, Fawzy SM. Aymptomtic celiac sprue in juvenile rheumatic diseases children. Int J Rheum Dis 2012; 15: 220-226.
[17]	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.
[18]	Lerner A, Matthias T. Rheumatoid arthritis-celiac disease relationship: joints get that gut feeling. Autoimm Rev. 2015: 14: 1038-1047.
[19]	Koning F, Thomas R, Rossjohn J, Toes RE. Coeliac disease and rheumatoid arthritis: common mechanisms, different antigens. Nat Rev Rheumatol 2015; 11: 450-461.
[20]	Richard-Miceli C, Criswell LA. Emerging patterns of genetic overlap across nautoimmune disorders. Genome Med 2014; 4: 6.
[21]	Gutierrez-Achury J, Coutinho de Almeida R,Wijmenga C. Shared genetics in coeliac disease and other immune-mediated diseases. J Intern Med 2011; 269: 591-603.
[22]	Zheng J, Petersen F, Yu X. The role of PTPN22 in autoimmunity: learning from mice. Autoimmun Rev 2014; 13: 266-271.
[23]	Zhernakova A, Stahl EA, Trynka G, Raychaudhuri S, Festen EA, Franke L, et al. Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. PLoS Genet 2011; 7 e1002004.
[24]	Cypers H, Van Praet L, Varkas G, Elewaut D. Relevance of the gut/joint axis for the management of spondyloarthritis in daily clinical practice. Curr Opin Rheumatol 2014; 26: 371-376.
[25]	De Wilde K, Debusschere K, Beeckman S, et al.Integrating the pathogenesis of spondyloarthritis: gut and joint united? Curr Opin Rheumatol. 2015; 27: 189-196.
[26]	Clemente JC, Ursell LK, Parfrey LW, Knight R. The impact of the gut microbiota on human health: an integrative view. Cell 2012; 148: 1258-1270.
[27]	Chen CY, Tsai CY. From endocrine to rheumatism: do gut hormones play roles in rheumatoid arthritis? Rheumatology (Oxford) 2014; 53: 205-212.
[28]	Armaka M, Apostolaki M, Jacques P, et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J Exp Med 2008; 205: 331-337.
[29]	Yoshida K, Korchynskyi O, Tak PP, Isozaki T, Ruth JH, Campbell PL, et al. Citrullination of epithelial neutrophil-activating peptide 78/CXCL5 results in conversion from a non-monocyte-recruiting chemokine to a monocyte-recruiting chemokine. Arthritis Rheum 2014; 66: 2716-2727.
[30]	Ciccia F, Guggino G, Rizzo A, et al. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis 2015; 74: 1739-1747.
[31]	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.
[32]	Lerner A, Matthias T. Possible association between celiac disease and bacterial transglutaminase in food processing: a hypothesis. Nutr Rev 2015; 73: 544-552.
[33]	Hvatum M, Kanerud L, Hällgren R, Brandtzaeg P. The gut-joint axis: cross reactive food antibodies in rheumatoid arthritis. Gut 2006; 55: 1240-1247.