Abstract
Spondyloarthritis (SpA) is a group of chronic, immune-mediated, inflammatory diseases affecting the bone, synovium, and enthesis. Microbiome, the community of microorganisms that has co-evolved with human hosts, plays a pivotal role in human health and disease. This invisible “essential organ” supplies the host with a myriad of chemicals and molecules. In turn, microbial metabolites can serve as messengers for microbes to communicate with each other and in the cross-talk with host cells. Gut dysbiosis in SpA is associated with altered microbial metabolites, and an accumulated body of research has contributed to the understanding that changes in intestinal microbiota can modulate disease pathogenesis. We review the novel findings from human and animal studies to provide an overview of the contribution of individual microbial metabolites and antigens to SpA.
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References
Terenzi R, Monti S, Tesei G, Carli L (2018) One year in review 2017: spondyloarthritis. Clin Exp Rheumatol 36(1):1–14
Smith JA, Colbert RA (2014) Review: the interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheumatol 66(2):231–241
Siebert S, Millar NL, McInnes IB (2019) Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation? Ann Rheum Dis 78(8):1015–1018
Salvucci E (2019) The human-microbiome superorganism and its modulation to restore health. Int J Food Sci Nutr 70(7):781–795
Wilkins LJ, Monga M, Miller AW (2019) Defining dysbiosis for a cluster of chronic diseases. Sci Rep 9(1):12918
Fragoulis GE, Liava C, Daoussis D, Akriviadis E, Garyfallos A, Dimitroulas T (2019) Inflammatory bowel diseases and spondyloarthropathies: from pathogenesis to treatment. World J Gastroenterol 25(18):2162–2176
Klingberg E, Magnusson MK, Strid H, Deminger A, Ståhl A, Sundin J, Simrén M, Carlsten H, Öhman L, Forsblad-d’Elia H (2019) A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin. Arthritis Res Ther 21(1):248
Stebbings S, Munro K, Simon MA, Tannock G, Highton J, Harmsen H, Welling G, Seksik P, Dore J, Grame G, Tilsala-Timisjarvi A (2002) Comparison of the faecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology (Oxford) 41(12):1395–1401
Kuberski TT et al (1983) Increased recovery of Klebsiella from the gastrointestinal tract of Reiter’s syndrome and ankylosing spondylitis patients. Rheumatol XXII(suppl_2):85–90
Li M et al (2019) Altered bacterial-fungal interkingdom networks in the guts of ankylosing spondylitis patients. mSystems 4(2):e00176–e00118
Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB (2015) Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol 67(1):128–139
Manasson J, Shen N, Garcia Ferrer HR, Ubeda C, Iraheta I, Heguy A, von Feldt JM, Espinoza LR, Garcia Kutzbach A, Segal LN, Ogdie A, Clemente JC, Scher JU (2018) Gut microbiota perturbations in reactive arthritis and postinfectious spondyloarthritis. Arthritis Rheumatol 70(2):242–254
Sanges M, Valente G, Rea M, Della Gatta R, de Franchis G, Sollazzo R, D'Arienzo A (2009) Probiotics in spondyloarthropathy associated with ulcerative colitis: a pilot study. Eur Rev Med Pharmacol Sci 13(3):233–234
Yang L, Liu B, Zheng J, Huang J, Zhao Q, Liu J, Su Z, Wang M, Cui Z, Wang T, Zhang W, Li Q, Lu H (2019) Rifaximin alters intestinal microbiota and prevents progression of ankylosing spondylitis in mice. Front Cell Infect Microbiol 9:44
Rath HC, Wilson KH, Sartor RB (1999) Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun 67(6):2969–2974
Gill T, Asquith M, Brooks SR, Rosenbaum JT, Colbert RA (2018) Effects of HLA–B27 on gut microbiota in experimental spondyloarthritis implicate an ecological model of dysbiosis. Arthritis & Rheumatology 70(4):555–565
Jadon DR (2018) Psoriatic arthritis and seronegative spondyloarthropathies. Med 46(4):237–242
Chen B, Li J, He C, Li D, Tong W, Zou Y, Xu W (2017) Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review). Mol Med Rep 15(4):1943–1951
Sheehan NJ (2004) The ramifications of HLA-B27. J R Soc Med 97(1):10–14
Akassou A, Bakri Y (2018) Does HLA-B27 status influence ankylosing spondylitis phenotype? Clin Med Insights Arthritis Musculoskelet Disord 11:1179544117751627
Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 63(5):1099–1112
Jadon DR, Sengupta R, Nightingale A, Lindsay M, Korendowych E, Robinson G, Jobling A, Shaddick G, Bi J, Winchester R, Giles JT, McHugh NJ (2017) Axial disease in psoriatic arthritis study: defining the clinical and radiographic phenotype of psoriatic spondyloarthritis. Ann Rheum Dis 76(4):701–707
van der Linden SM et al (1984) The risk of developing ankylosing spondylitis in HLA-B27 positive individuals. A comparison of relatives of spondylitis patients with the general population. Arthritis Rheum 27(3):241–249
Cortes A et al (2013) Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 45(7):730–738
FitzGerald O, Haroon M, Giles JT, Winchester R (2015) Concepts of pathogenesis in psoriatic arthritis: genotype determines clinical phenotype. Arthritis Res Ther 17(1):115
Busch R, Kollnberger S, Mellins ED (2019) HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications. Nat Rev Rheumatol 15(6):364–381
Fujinami RS, von Herrath MG, Christen U, Whitton JL (2006) Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev 19(1):80–94
Rashid T, Wilson C, Ebringer A (2013) The link between ankylosing spondylitis, Crohn’s disease, <i > Klebsiella</i>, and starch consumption. Clin Dev Immunol 2013:872632
Tiwana H, Wilson C, Walmsley RS, Wakefield AJ, Smith MSN, Cox NL, Hudson MJ, Ebringer A (1997) Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn’s disease and ulcerative colitis. Rheumatol Int 17(1):11–16
Zhu W, He X, Cheng K, Zhang L, Chen D, Wang X, Qiu G, Cao X, Weng X (2019) Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res 7:22
Kollnberger S, Chan A, Sun MY, Ye Chen L, Wright C, di Gleria K, McMichael A, Bowness P (2007) Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur J Immunol 37(5):1313–1322
Ridley A, Hatano H, Wong-Baeza I, Shaw J, Matthews KK, al-Mossawi H, Ladell K, Price DA, Bowness P, Kollnberger S (2016) Activation-induced killer cell immunoglobulin-like receptor 3DL2 binding to HLA-B27 licenses pathogenic T cell differentiation in spondyloarthritis. Arthritis Rheumatol 68(4):901–914
DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA (2009) HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum 60(9):2633–2643
Svenungsson B (1995) Reactive arthritis. Int J STD AIDS 6(3):156–160
Banicioiu-Covei S, Vreju FA, Ciurea P (2015) Predictive factors for the evolution of reactive arthritis to ankylosing spondylitis. Curr Health Sci J 41(2):104–108
Pacheco-Tena C, Alvarado de la Barrera C, López-Vidal Y, Vázquez-Mellado J, Richaud-Patin Y, Amieva RI, Llorente L, Martínez A, Zúñiga J, Cifuentes-Alvarado M, Burgos-Vargas R (2001) Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathies. Rheumatol (Oxford) 40(8):920–927
Granfors K, Jalkanen S, von Essen R, Lahesmaa-Rantala R, Isomäki O, Pekkola-Heino K, Merilahti-Palo R, Saario R, Isomäki H, Toivanen A (1989) Yersinia antigens in synovial-fluid cells from patients with reactive arthritis. N Engl J Med 320(4):216–221
Granfors K, Jalkanen S, Mäki-Ikola O, Lahesmaa-Rantala R, Saario R, Toivanen A, Lindberg AA, von Essen R, Isomaki H, Arnold WJ (1990) Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis. Lancet 335(8691):685–688
Kaeley N, Kumar M, Bhardwaj BB, Nagasubramanyam V (2019) Shigella flexneri associated reactive arthritis - GI transmitted or sexually transmitted? J Family Med Prim Care 8(3):1250–1252
Kumar P, Khanna G, Batra S, Sharma VK, Rastogi S (2016) Chlamydia trachomatis elementary bodies in synovial fluid of patients with reactive arthritis and undifferentiated spondyloarthropathy in India. Int J Rheum Dis 19(5):506–511
Elwell C, Mirrashidi K, Engel J (2016) Chlamydia cell biology and pathogenesis. Nat Rev Microbiol 14(6):385–400
Saxena S, Aggarwal A, Misra R (2005) Outer membrane protein of salmonella is the major antigenic target in patients with salmonella induced reactive arthritis. J Rheumatol 32(1):86–92
Mertz AK et al (1998) Characterization of the synovial T cell response to various recombinant Yersinia antigens in Yersinia enterocolitica-triggered reactive arthritis. Heat-shock protein 60 drives a major immune response. Arthritis Rheum 41(2):315–326
Thiel A, Wu P, Lauster R, Braun J, Radbruch A, Sieper J (2000) Analysis of the antigen-specific T cell response in reactive arthritis by flow cytometry. Arthritis Rheum 43(12):2834–2842
Chaurasia S, Shasany AK, Aggarwal A, Misra R (2016) Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy. Clin Exp Immunol 185(2):210–218
Mäki-Ikola O, Lehtinen K, Granfors K, Vainionpää R, Toivanen P (1991) Bacterial antibodies in ankylosing spondylitis. Clin Exp Immunol 84(3):472–475
Dominguez-López ML et al (2002) IgG antibodies to enterobacteria 60 kDa heat shock proteins in the sera of HLA-B27 positive ankylosing spondylitis patients. Scand J Rheumatol 31(5):260–265
Zambrano-Zaragoza JF, de Jesus Duran-Avelar M, Rodriguez-Ocampo AN, Garcia-Latorre E, Burgos-Vargas R, Dominguez-Lopez ML, Pena-Virgen S, Vibanco-Perez N (2009) The 30-kDa band from Salmonella typhimurium: IgM, IgA and IgG antibody response in patients with ankylosing spondylitis. Rheumatol (Oxford) 48(7):748–754
Durán-Avelar MJ, Vibanco-Pérez N, Rodríguez-Ocampo AN, Peña-Virgen S, Zambrano-Zaragoza JF (2013) Lymphoproliferative response to the 30-kDa protein and a crude lysate from Salmonella typhimurium in patients with ankylosing spondylitis. Scand J Rheumatol 42(3):232–234
Sahin N, Salli A, Enginar AU, Ugurlu H (2009) Reactive arthritis following tetanus vaccination: a case report. Mod Rheumatol 19(2):209–211
Logan D, McKee PJ (2006) Poststreptococcal reactive arthritis. J Am Podiatr Med Assoc 96(4):362–366
Chou YS, Horng CT, Huang HS, Hu SC, Chen JT, Tsai ML (2010) Reactive arthritis following Streptococcus viridans urinary tract infection. Ocul Immunol Inflamm 18(1):52–53
Haapasalo K et al (2018) The psoriasis risk allele HLA-C*06:02 shows evidence of association with chronic or recurrent streptococcal tonsillitis. Infect Immun 86(10)
Sigurdardottir SL, Thorleifsdottir RH, Valdimarsson H, Johnston A (2013) The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells. Clin Exp Immunol 174(1):139–151
Dagan A, Dahan S, Shemer A, Langevitz P, Hellou T, Davidson T, Shoenfeld Y, Shovman O (2019) Acute onset of psoriatic spondyloarthritis as a new manifestation of post-streptococcal reactive arthritis: a case series. Clin Rheumatol 38(9):2367–2372
Muto M, Fujikura Y, Hamamoto Y, Ichimiya M, Ohmura A, Sasazuki T, Fukumoto T, Asagami C (1996) Immune response to Streptococcus pyogenes and the susceptibility to psoriasis. Australas J Dermatol 37(Suppl 1):S54–S55
Muto M, Date Y, Ichimiya M, Moriwaki Y, Mori K, Kamikawaji N, Kimura A, Sasazuki T, Asagami C (1996) Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207. Tissue Antigens 48(6):645–650
Carrasco S, Neves FS, Fonseca MH, Gonçalves CR, Saad CG, Sampaio-Barros PD, Goldenstein-Schainberg C (2011) Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a gram-positive inflammatory trigger? Clin Exp Rheumatol 29(6):958–962
Candia L et al (2007) Toll-like receptor-2 expression is upregulated in antigen-presenting cells from patients with psoriatic arthritis: a pathogenic role for innate immunity? J Rheumatol 34(2):374
Yang X, Xie L, Li Y, Wei C (2009) More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body. PLoS One 4(6):e6074
Joice R, Yasuda K, Shafquat A, Morgan XC, Huttenhower C (2014) Determining microbial products and identifying molecular targets in the human microbiome. Cell Metab 20(5):731–741
Roager HM, Dragsted LO (2019) Diet-derived microbial metabolites in health and disease. Nutr Bull 44(3):216–227
Kaur, A., Alterations in the amounts of microbial metabolites in different regions of the mouse large intestine using variably fermentable fibres. Bioact carbohydr Diet Fibre, 2018. v. 13: p. pp. 7-13-2018 v.13.
Fardina Malik, J.M., Alberto Herrera, Malavika Attur, Soumya M. Reddy, Lu Yang, Sergei Koralov and Jose U. Scher, Effects of fatty acid supplementation in modulation of gut microbiome and T-regulatory cells in health and psoriatic disease, in American College of Rheumatology. 2018.
Asquith M, Davin S, Stauffer P, Michell C, Janowitz C, Lin P, Ensign-Lewis J, Kinchen JM, Koop DR, Rosenbaum JT (2017) Intestinal metabolites are profoundly altered in the context of HLA-B27 expression and functionally modulate disease in a rat model of spondyloarthritis. Arthritis Rheumatol 69(10):1984–1995
Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS (2013) The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 341(6145):569–573
Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, Rudensky AY (2013) Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 504(7480):451–455
Chen G, Ran X, Li B, Li Y, He D, Huang B, Fu S, Liu J, Wang W (2018) Sodium butyrate inhibits inflammation and maintains epithelium barrier integrity in a TNBS-induced inflammatory bowel disease mice model. EBioMed 30:317–325
Chen L, Sun M, Wu W, Yang W, Huang X, Xiao Y, Ma C, Xu L, Yao S, Liu Z, Cong Y (2019) Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells’ differentiation and function in induction of colitis. Inflamm Bowel Dis 25(9):1450–1461
Nastasi C, Fredholm S, Willerslev-Olsen A, Hansen M, Bonefeld CM, Geisler C, Andersen MH, Ødum N, Woetmann A (2017) Butyrate and propionate inhibit antigen-specific CD8(+) T cell activation by suppressing IL-12 production by antigen-presenting cells. Sci Rep 7(1):14516
Qiu J et al (2019) Acetate promotes T cell effector function during glucose restriction. Cell Rep 27(7):2063–2074.e5
Ulven T (2012) Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets. Front Endocrinol (Lausanne) 3:111
Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, Nakanishi Y, Uetake C, Kato K, Kato T, Takahashi M, Fukuda NN, Murakami S, Miyauchi E, Hino S, Atarashi K, Onawa S, Fujimura Y, Lockett T, Clarke JM, Topping DL, Tomita M, Hori S, Ohara O, Morita T, Koseki H, Kikuchi J, Honda K, Hase K, Ohno H (2013) Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature 504(7480):446–450
Briot K, Roux C (2015) Inflammation, bone loss and fracture risk in spondyloarthritis. RMD Open 1(1):e000052
Frediani B, Allegri A, Falsetti P, Storri L, Bisogno S, Baldi F, Filipponi P, Marcolongo R (2001) Bone mineral density in patients with psoriatic arthritis. J Rheumatol 28(1):138–143
Lucas S, Omata Y, Hofmann J, Böttcher M, Iljazovic A, Sarter K, Albrecht O, Schulz O, Krishnacoumar B, Krönke G, Herrmann M, Mougiakakos D, Strowig T, Schett G, Zaiss MM (2018) Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun 9(1):55
Yang L, Fanok MH, Mediero-Munoz A, Fogli LK, Corciulo C, Abdollahi S, Cronstein BN, Scher JU, Koralov SB (2018) Augmented Th17 differentiation leads to cutaneous and synovio-entheseal inflammation in a novel model of psoriatic arthritis. Arthritis Rheumatol 70(6):855–867
Tyagi AM et al (2018) The microbial metabolite butyrate stimulates bone formation via T regulatory cell-mediated regulation of WNT10B expression. Immun 49(6):1116–1131.e7
Stoll ML, Kumar R, Lefkowitz EJ, Cron RQ, Morrow CD, Barnes S (2016) Fecal metabolomics in pediatric spondyloarthritis implicate decreased metabolic diversity and altered tryptophan metabolism as pathogenic factors. Genes Immun 17(7):400–405
Senna MK, Olama SM, El-Arman M (2012) Serum melatonin level in ankylosing spondylitis: is it increased in active disease? Rheumatol Int 32(11):3429–3433
Klavdianou K, Liossis SN, Papachristou DJ, Theocharis G, Sirinian C, Kottorou A, Filippopoulou A, Andonopoulos AP, Daoussis D (2016) Decreased serotonin levels and serotonin-mediated osteoblastic inhibitory signaling in patients with ankylosing spondylitis. J Bone Miner Res 31(3):630–639
Aylward M, Maddock J (1974) Plasma l-tryptophan concentrations in chronic rheumatic diseases and the effects of some antirheumatic drugs on the binding of the amino-acid to plasma proteins in vivo and in vitro*. Rheumatol 13(2):62–74
Bertazzo A et al (1999) Tryptophan catabolism in synovial fluid of various arthropathies and its relationship with inflammatory cytokines. Adv Exp Med Biol 467:565–570
Auckland G (1969) Psoriasis and arthritis: treatment with low tryptophan diet. Br J Dermatol 81(5):388–389
Mellor AL, Munn DH (2003) Tryptophan catabolism and regulation of adaptive immunity. J Immunol 170(12):5809–5813
Sorgdrager FJH, Naudé PJW, Kema IP, Nollen EA, Deyn PPD (2019) Tryptophan metabolism in inflammaging: from biomarker to therapeutic target. Front Immunol 10:2565
Coras R, Kavanaugh A, Boyd T, Huynh D, Lagerborg KA, Xu YJ, Rosenthal SB, Jain M, Guma M (2019) Choline metabolite, trimethylamine N-oxide (TMAO), is associated with inflammation in psoriatic arthritis. Clin Exp Rheumatol 37(3):481–484
Ierardi E, Sorrentino C, Principi M, Giorgio F, Losurdo G, di Leo A (2015) Intestinal microbial metabolism of phosphatidylcholine: a novel insight in the cardiovascular risk scenario. Hepatobiliary Surg Nutr 4(4):289–292
Wu K, Yuan Y, Yu H, Dai X, Wang S, Sun Z, Wang F, Fei H, Lin Q, Jiang H, Chen T (2020) Gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice. Blood 136:501–515
Sitaraman R (2013) Phospholipid catabolism by gut microbiota and the risk of cardiovascular disease. J Med Microbiol 62(6):948–950
Tofalo R, Cocchi S, Suzzi G (2019) Polyamines and gut microbiota. Front Nutr 6:16
Wang, C., et al., Metabolic and epigenomic regulation of Th17/Treg balance by the polyamine pathway. bioRxiv, 2020: p. 2020.01.23.911966.
Lou F, Sun Y, Xu Z, Niu L, Wang Z, Deng S, Liu Z, Zhou H, Bai J, Yin Q, Cai X, Sun L, Wang H, Li Q, Wu Z, Chen X, Gu J, Shi YL, Tao W, Ginhoux F, Wang H (2020) Excessive polyamine generation in keratinocytes promotes self-RNA sensing by dendritic cells in psoriasis. Immun 53:204–216.e10
Scher JU, Ogdie A, Merola JF, Ritchlin C (2019) Preventing psoriatic arthritis: focusing on patients with psoriasis at increased risk of transition. Nat Rev Rheumatol 15(3):153–166
Liu B, Jiang X, Cai L, Zhao X, Dai Z, Wu G, Li X (2019) Putrescine mitigates intestinal atrophy through suppressing inflammatory response in weanling piglets. J Animal Sci Biotechnol 10(1):69
Li G et al (2020) Spermidine suppresses inflammatory DC function by activating the FOXO3 pathway and counteracts autoimmunity. iSci 23(1):100807
Funding
Work in the Koralov and Scher laboratories was supported by joint grants from the Judith and Stewart Colton Center for Autoimmunity and NPF Psoriatic Arthritis Diagnostic Test Grant. Research in the Koralov laboratory is further supported by NIH R01HL125816, funding from Drs. Martin and Dorothy Spatz Foundation, LEO Foundation (LF-OC-20-000351), and the Irma T. Hirschl and Monique Weill-Caulier Trust. Work in the Chang Lab is supported by NIH R01AR070131 and R01AR073851 grants. Research in the Scher laboratory is further supported by NIH/NIAMS R01AR074500, the Snyder Family Foundation, and the Riley Family Foundation.
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Drs. Scher and Koralov are co-authors on US Patent 10,226,443 “Methods for treating psoriatic arthritis.” The other authors declare no competing interests.
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This article is a contribution to the Special issue on: Spondyloarthritis - Guest Editors: Robert Inman & Nigil Haroon
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Yang, K.L., Lejeune, A., Chang, G. et al. Microbial-derived antigens and metabolites in spondyloarthritis. Semin Immunopathol 43, 163–172 (2021). https://doi.org/10.1007/s00281-021-00844-1
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DOI: https://doi.org/10.1007/s00281-021-00844-1