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Stress proteins in the pathogenesis of spondyloarthritis

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Abstract

Spondyloarthritis is an autoinflammatory rheumatic disease in which arthritis and osteoproliferation lead the patients who suffer from it to chronic disability. This disease is associated with the expression of class I MHC molecule HLA-B27, which tends to be misfolded in the endoplasmic reticulum and, therefore, expressed in aberrant forms. This phenomena lead to endoplasmic reticulum stress, which in time, evokes a whole response to cellular injury. Under these conditions, the molecules involved in restoring cell homeostasis play a key role. Such is the case of the “heat-shock proteins”, which usually regulate protein folding, but also have important immunomodulatory functions, as well as some roles in tissue modeling. In this review, we attempt to summarize the involvement of cell stress and heat-shock proteins in the homeostatic disturbances and pathological conditions associated with this disease.

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References

  1. Dougados M, Baeten D (2011) Spondyloarthritis. Lancet 377:2127–2137. https://doi.org/10.1016/S0140-6736(11)60071-8

    Article  PubMed  Google Scholar 

  2. van der Linden S, van der Heijde D (1998) Ankylosing spondylitis: clinical features. Rheum Dis Clin North Am 24:663–676

    Article  PubMed  Google Scholar 

  3. Rudwaleit M, van der Heijde D, Landewé R et al (2009) The development of assessment of Spondyloarthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 68:777–783. https://doi.org/10.1136/ard.2009.108233

    Article  CAS  PubMed  Google Scholar 

  4. Burgos-Vargas R (2013) Spondyloarthritis: from undifferentiated SpA to ankylosing spondylitis. Nat Rev Rheumatol 9:639–641. https://doi.org/10.1038/nrrheum.2013.146

    Article  PubMed  Google Scholar 

  5. Baeten D, Breban M, Lories R et al (2013) Are spondyloarthritides related but distinct conditions or a single disease with a heterogeneous phenotype? Arthritis Rheum 65:12–20. https://doi.org/10.1002/art.37829

    Article  PubMed  Google Scholar 

  6. Asquith M, Elewaut D, Lin P, Rosenbaum JT (2014) The role of the gut and microbes in the pathogenesis of spondyloarthritis. Best Pract Res Clin Rheumatol 28:687–702. https://doi.org/10.1016/j.berh.2014.10.018

    Article  PubMed  PubMed Central  Google Scholar 

  7. Raychaudhuri SP, Raychaudhuri SK (2016) IL-23/IL-17 axis in spondyloarthritis-bench to bedside. Clin Rheumatol 35:1437–1441. https://doi.org/10.1007/s10067-016-3263-4

    Article  PubMed  Google Scholar 

  8. Speca S, Dubuquoy L (2017) Chronic bowel inflammation and inflammatory joint disease: pathophysiology. Jt Bone Spine. https://doi.org/10.1016/j.jbspin.2016.12.016

    Article  Google Scholar 

  9. Baerlecken NT, Nothdorft S, Stummvoll GH et al (2014) Autoantibodies against CD74 in spondyloarthritis. Ann Rheum Dis 73:1211–1214. https://doi.org/10.1136/annrheumdis-2012-202208

    Article  CAS  PubMed  Google Scholar 

  10. de Winter JJ, van de Sande MG, Baerlecken N et al (2018) Anti-CD74 antibodies have no diagnostic value in early axial spondyloarthritis: data from the spondyloarthritis caught early (SPACE) cohort. Arthritis Res Ther 20:1–8. https://doi.org/10.1186/s13075-018-1535-x

    Article  CAS  Google Scholar 

  11. Lories RJ, Haroon N (2014) Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol 28:765–777. https://doi.org/10.1016/j.berh.2014.10.008

    Article  PubMed  Google Scholar 

  12. Tsui FWL, Tsui HW, Heras F, Las et al (2014) Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spondylitis. Ann Rheum Dis 73:1873–1879. https://doi.org/10.1136/annrheumdis-2013-203630

    Article  CAS  PubMed  Google Scholar 

  13. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045. https://doi.org/10.1146/annurev.iy.12.040194.005015

    Article  CAS  PubMed  Google Scholar 

  14. Schlosstein L, Terasaki P, Bluestone R, Pearson C (1973) High Association of an HL-A Antigen, W27, with Ankylosing Spondylitis. N Engl J Med 288:704–706

    Article  CAS  PubMed  Google Scholar 

  15. Maclean I, Iqball S, Woo P et al (1993) HLA-B27 subtypes in the spondyloarthropathies. Clin Exp Immunol 91:214–219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Stone MA, Payne U, Schentag C et al (2004) Comparative immune responses to candidate arthritogenic bacteria do not confirm a dominant role for Klebsiella pneumonia in the pathogenesis of familial ankylosing spondylitis. Rheumatology 43:148–155. https://doi.org/10.1093/rheumatology/keg482

    Article  CAS  PubMed  Google Scholar 

  17. Cancino-Diaz ME, Pérez-Salazar J, Domínguez-López ML et al (1998) Antibody response to Klebsiella pneumoniae 60 kDa protein in familial and sporadic ankylosing spondylitis: role of HLA-B27 and characterization as a GroEL-like protein. J Rheumatol 25:1756–1764

    CAS  PubMed  Google Scholar 

  18. Rashid T, Ebringer A (2007) Ankylosing spondylitis is linked to Klebsiella—the evidence. Clin Rheumatol 26:858–864. https://doi.org/10.1007/s10067-006-0488-7

    Article  PubMed  Google Scholar 

  19. Ebringer A (1992) Ankylosing spondylitis is caused by Klebsiella, evidence from immunogenic, microbiologic and serologic studies. Rheum Dis Clin North Am 18:105–121

    CAS  PubMed  Google Scholar 

  20. Trull a, Panayi EG et al (1984) HLA-B27 and the immune response to enterobacterial antigens in ankylosing spondylitis. Clin Exp Immunol 55:74–80

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Mäki-Ikola O, Lehtinen K, Granfors K et al (1991) Bacterial antibodies in ankylosing spondylitis. Clin Exp Immunol 84:472–475

    PubMed  PubMed Central  Google Scholar 

  22. Parra-Campos V, Escobar-Gutiérrez A, Dominguez-Lopez ML et al (1996) Antibody response to nitrogenase-positive and negative Klebsiella pneumoniae strains in juvenile-onset ankylosing spondylitis patients and their first degree relatives: lack of differential recognition of the bacterial nitrogenase. Rev Latinoam Microbiol 38:121–127

    CAS  PubMed  Google Scholar 

  23. Hammer RE, Maika SD, Richardson JA et al (1990) Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: An animal model of HLA-B27-associated human disorders. Cell 63:1099–1112. https://doi.org/10.1016/0092-8674(90)90512-D

    Article  CAS  PubMed  Google Scholar 

  24. Bowness P (2015) HLA-B27. Annu Rev Immunol 33:29–48. https://doi.org/10.1146/annurev-immunol-032414-112110

    Article  CAS  PubMed  Google Scholar 

  25. Dangoria NS, Delay ML, Kingsbury DJ et al (2002) HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum. J Biol Chem 277(26):23459–23468

    Article  CAS  PubMed  Google Scholar 

  26. Kollnberger S, Bird L, Sun MY et al (2002) Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum 46:2972–2982. https://doi.org/10.1002/art.10605

    Article  CAS  PubMed  Google Scholar 

  27. Turner MJ, Sowders DP, DeLay ML et al (2005) HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 175:2438–2448. https://doi.org/10.4049/jimmunol.175.4.2438

    Article  CAS  PubMed  Google Scholar 

  28. Ciccia F, Haroon N (2016) Autophagy in the pathogenesis of ankylosing spondylitis. Clin Rheumatol 35:1433–1436. https://doi.org/10.1007/s10067-016-3262-5

    Article  PubMed  Google Scholar 

  29. Bettigole SE, Glimcher LH (2014) Endoplasmic reticulum stress in immunity. Annu Rev Immunol. https://doi.org/10.1146/annurev-immunol-032414-112116

    Article  PubMed  Google Scholar 

  30. Grootjans J, Kaser A, Kaufman RJ, Blumberg RS (2016) The unfolded protein response in immunity and inflammation. Nat Rev Immunol 16:469–484. https://doi.org/10.1038/nri.2016.62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Meusser B, Hirsch C, Jarosch E, Sommer T (2005) ERAD: The long road to destruction. Nat Cell Biol 7:766–772. https://doi.org/10.1038/ncb0805-766

    Article  CAS  PubMed  Google Scholar 

  32. DeLay ML, Turner MJ, Klenk EI et al (2009) HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum 60:2633–2643. https://doi.org/10.1002/art.24763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sherlock JP, Joyce-Shaikh B, Turner SP et al (2012) IL-23 induces spondyloarthropathy by acting on ROR-γt + CD3 + CD4-CD8- entheseal resident T cells. Nat Med 18:1069–1076. https://doi.org/10.1038/nm.2817

    Article  CAS  PubMed  Google Scholar 

  34. Smith JA, Colbert RA (2014) The interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheumatol 66:231–241. https://doi.org/10.1002/art.38291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zeng L, Lindstrom MJ, Smith JA (2011) Ankylosing spondylitis macrophage production of higher levels of interleukin-23 in response to lipopolysaccharide without induction of a significant unfolded protein response 63:3807–3817. https://doi.org/10.1002/art.30593

  36. Ciccia F, Accardo-Palumbo A, Rizzo A et al (2014) Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann Rheum Dis 73:1566–1574. https://doi.org/10.1136/annrheumdis-2012-202925

    Article  CAS  PubMed  Google Scholar 

  37. Dong W, Zhang Y, Yan M et al (2008) Upregulation of 78-kDa glucose-regulated protein in macrophages in peripheral joints of active ankylosing spondylitis. Scand J Rheumatol 37:427–434. https://doi.org/10.1080/03009740802213310

    Article  CAS  PubMed  Google Scholar 

  38. Rezaiemanesh A, Mahmoudi M, Amirzargar AA et al (2016) Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23. Mod Rheumatol 27(5):862–886. https://doi.org/10.1080/14397595.2016.1259716

    Article  CAS  PubMed  Google Scholar 

  39. Neerinckx B, Carter S, Lories R (2014) IL-23 expression and activation of autophagy in synovium and PBMCs of HLA-B27 positive patients with ankylosing spondylitis. Response to:’Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of pati. Ann Rheum Dis 73:e68. https://doi.org/10.1136/annrheumdis-2014-206277

    Article  CAS  PubMed  Google Scholar 

  40. Levine B, Mizushima N, Virgin HW (2011) Autophagy in immunity and inflammation. Nature 469:323–335. https://doi.org/10.1038/nature09782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Dokladny K, Myers OB, Moseley PL (2015) Heat shock response and autophagy. Autophagy 11:200–213

    Article  PubMed  PubMed Central  Google Scholar 

  42. Park MC, Kim HW, Lee SW et al (2017) Defective autophagy activity and its association with spinal damage in patients with ankylosing spondylitis. Jt Bone Spine 84:583–587. https://doi.org/10.1016/j.jbspin.2016.09.005

    Article  CAS  Google Scholar 

  43. Cooney R, Baker J, Brain O et al (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16:90–97. https://doi.org/10.1038/nm.2069

    Article  CAS  PubMed  Google Scholar 

  44. Brain O, Owens BMJ, Pichulik T et al (2013) The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release. Immunity 39:521–536. https://doi.org/10.1016/j.immuni.2013.08.035

    Article  CAS  PubMed  Google Scholar 

  45. Reveille J, Sims A-M, Danoy P et al (2010) Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet 42:123–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Alvarez-Navarro C, López de Castro JA (2014) ERAP1 structure, function and pathogenetic role in ankylosing spondylitis and other MHC-associated diseases. Mol Immunol 57:12–21. https://doi.org/10.1016/j.molimm.2013.06.012

    Article  CAS  PubMed  Google Scholar 

  47. Bettencourt BF, Rocha FL, Alves H et al (2013) Protective effect of an ERAP1 haplotype in ankylosing spondylitis: Investigating non-MHC genes in HLA-B27-positive individuals. Rheumatology 52(12):2168–2176. https://doi.org/10.1093/rheumatology/ket269

    Article  CAS  PubMed  Google Scholar 

  48. Haroon N, Tsui FW, Uchanska-Ziegler B et al (2012) Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interaction with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann Rheum Dis 71:589–595. https://doi.org/10.1136/annrheumdis-2011-200347

    Article  CAS  PubMed  Google Scholar 

  49. Cortes A, Pulit SL, Leo PJ et al (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nat Commun. https://doi.org/10.1038/ncomms8146

    Article  PubMed  PubMed Central  Google Scholar 

  50. Kenna TJ, Lau MC, Keith P et al (2015) Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis. Genes Immun 16:35–42. https://doi.org/10.1038/gene.2014.62

    Article  CAS  PubMed  Google Scholar 

  51. Robinson PC, Lau E, Keith P et al (2015) ERAP2 functional knockout in humans does not alter surface heavy chains or HLA-b27, inflammatory cytokines or endoplasmic reticulum stress markers. Ann Rheum Dis 74:2092–2095. https://doi.org/10.1136/annrheumdis-2015-207467

    Article  CAS  PubMed  Google Scholar 

  52. Zhang Z, Ciccia F, Zeng F et al (2017) Functional interaction of ERAP2 and HLA-B27 activates the unfolded protein response. Arthritis Rheumatol 69:1009–1015. https://doi.org/10.1002/art.40033

    Article  CAS  PubMed  Google Scholar 

  53. Fink AL (1999) Chaperone-mediated protein folding. Physiol Rev 79:425–449. https://doi.org/10.1091/mbc.4.6.647

    Article  CAS  PubMed  Google Scholar 

  54. Liu Y, Chang A (2008) Heat shock response relieves ER stress. EMBO J 27:1049–1059. https://doi.org/10.1038/emboj.2008.42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Van Eden W, Spiering R, Broere F, Van Der Zee R (2012) A case of mistaken identity: HSPs are no DAMPs but DAMPERs. Cell Stress Chaperones 17:281–292. https://doi.org/10.1007/s12192-011-0311-5

    Article  PubMed  Google Scholar 

  56. Srivastava PK (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol. https://doi.org/10.1038/nri749

    Article  PubMed  Google Scholar 

  57. Gaston J (1991) Heat shock proteins and autoimmunity. Semin Immunol 3:35–42

    CAS  PubMed  Google Scholar 

  58. de Graeff-Meeder ER, Voorhorst M, van Eden W et al (1990) Antibodies to the mycobacterial 65-kd heat-shock protein are reactive with synovial tissue of adjuvant arthritic rats and patients with rheumatoid arthritis and osteoarthritis. Am J Pathol 137:1013–1017

    PubMed  PubMed Central  Google Scholar 

  59. Kolb H, Chen W, Syldath U et al (2017) Human 60-kDa heat-shock protein: a danger signal to the innate immune system. J Immunol 162:3212–3219

    Google Scholar 

  60. Cancino-Diaz M, Curiel-Quesada E, García-Latorre E, Jimenez-Zamudio L (1998) Cloning and sequencing of the gene that codes for the Klebsiella pneumoniae GroEL-like protein associated with ankylosing spondylitis. Microb Pathog 25:23–32

    Article  CAS  PubMed  Google Scholar 

  61. Cancino-Diaz M, Ayala-Narvaez H, Burgos-Vargas R et al (2000) Recognition of B cell epitopes of the Klebsiella pneumoniae GroEL-like protein by HLA-B27 positive subjects. Microb Pathog 28:211–220

    Article  CAS  PubMed  Google Scholar 

  62. Scofield R, Kurien B, Gross T et al (1995) HLA-B27 binding of peptide from its own sequence and similar peptides from bacteria: implications for spondyloarthropathies. Lancet 345:1542–1544

    Article  CAS  PubMed  Google Scholar 

  63. Domínguez-López ML, Cancino-Diaz ME, Jiménez-Zamudio L et al (2000) Cellular immune response to Klebsiella pneumoniae antigens in HLA-B27 positive ankylosing spondylitis patients. J Rheumatol 27:1453–1460

    PubMed  Google Scholar 

  64. Zambrano-Zaragoza F, García-Latorre E, Domínguez-López ML et al (2005) CD4 and CD8 T cell response to the rHSP60 from Klebsiella pneumoniae in peripheral blood mononuclear cells from patients with ankylosing spondylitis. Rev Investig Clínica 57:555–562

    CAS  Google Scholar 

  65. Dominguez-Lopez ML, Burgos-Vargas R, Galicia-Serrano H 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 31:260–265. https://doi.org/10.1080/030097402760375133

    Article  CAS  PubMed  Google Scholar 

  66. Domínguez-López ML, Ortega-Ortega Y, Manríquez-Raya J et al (2009) Antibodies against recombinant heat shock proteins of 60 kDa from enterobacteria in the sera and synovial fluid of HLA-B27 positive ankylosing spondylitis patients. Clin Exp Rheumatol 27:626–632

    PubMed  Google Scholar 

  67. Pacheco-Tena C, Alvarado De La Barrera C, López-Vidal Y et al (2001) Bacterial DNA in synovial fluid cells of patients with juvenile onset spondyloarthropathies. Rheumatology 40:920–927

    Article  CAS  PubMed  Google Scholar 

  68. Hjelholt A, Carlsen T, Deleuran B et al (2013) Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis. PLoS One 8:e56210. https://doi.org/10.1371/journal.pone.0056210 doi

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Carlsen T, Hjelholt A, Jurik AG et al (2013) IgG subclass antibodies to human and bacterial HSP60 are not associated with disease activity and progression over time in axial spondyloarthritis. Arthritis Res Ther 15:R61

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Priya S, Sharma SK, Goloubinoff P (2013) Molecular chaperones as enzymes that catalytically unfold misfolded polypeptides. FEBS Lett 587:1981–1987. https://doi.org/10.1016/j.febslet.2013.05.014

    Article  CAS  PubMed  Google Scholar 

  71. Dokladny K, Zuhl MN, Mandell M et al (2013) Regulatory coordination between two major intracellular homeostatic systems: Heat shock response and autophagy. J Biol Chem 288:14959–14972. https://doi.org/10.1074/jbc.M113.462408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kim H, Choi J, Ryu J et al (2009) Activation of autophagy during glutamate-induced HT22 cell death. Biochem Biophys Res Commun 388:339–344. https://doi.org/10.1016/j.bbrc.2009.08.007

    Article  CAS  PubMed  Google Scholar 

  73. Cappelletti C, Galbardi B, Kapetis D et al (2014) Autophagy, inflammation and innate immunity in inflammatory myopathies. PLoS One. https://doi.org/10.1371/journal.pone.0111490

    Article  PubMed  PubMed Central  Google Scholar 

  74. Cheng MY, Hartl FU, Martin J et al (1989) Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 337:620–625

    Article  CAS  PubMed  Google Scholar 

  75. Langer T, Pfeifer G, Martin J et al (1992) Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. EMBO J 11:4757–4765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pfister G, Stroh CM, Perschinka H et al (2005) Detection of HSP60 on the membrane surface of stressed human endothelial cells by atomic force and confocal microscopy. J Cell Sci 118:1587–1594. https://doi.org/10.1242/jcs.02292

    Article  CAS  PubMed  Google Scholar 

  77. Poccia F, Piselli P, Vendetti S et al (1996) Heat-shock protein expression on the membrane of T cells undergoing apoptosis. Immunology 88:6–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Zhu H, Fang X, Zhang D et al (2016) Membrane-bound heat shock proteins facilitate the uptake of dying cells and cross-presentation of cellular antigen. Apoptosis 21:96–109. https://doi.org/10.1007/s10495-015-1187-0

    Article  CAS  PubMed  Google Scholar 

  79. Habich C, Baumgart K, Kolb H, Burkart V (2002) The receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins. J Immunol 168:569–576. https://doi.org/10.4049/jimmunol.168.2.569

    Article  CAS  PubMed  Google Scholar 

  80. Vabulas RM, Ahmad-Nejad P, Da Costa C et al (2001) Endocytosed HSP60s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276:31332–31339. https://doi.org/10.1074/jbc.M103217200

    Article  CAS  PubMed  Google Scholar 

  81. Zanin-Zhorov A, Nussbaum G, Franitza S et al (2003) T cells respond to heat shock protein 60 via TLR2: activation of adhesion and inhibition of chemokine receptors. FASEB J 17:1567–1569. https://doi.org/10.1096/fj.02-1139fje

    Article  CAS  PubMed  Google Scholar 

  82. Quintana FJ, Mimran A, Carmi P et al (2008) HSP60 as a target of anti-ergotypic regulatory T cells. PLoS One. https://doi.org/10.1371/journal.pone.0004026

    Article  PubMed  PubMed Central  Google Scholar 

  83. Tamura Y, Torigoe T, Kukita K et al (2012) Heat-shock proteins as endogenous ligands building a bridge between innate and adaptive immunity. Immunotherapy 4:841–852. https://doi.org/10.2217/imt.12.75

    Article  CAS  PubMed  Google Scholar 

  84. Quintana FJ, Cohen IR (2011) The HSP60 immune system network. Trends Immunol 32:89–95. https://doi.org/10.1016/j.it.2010.11.001

    Article  CAS  PubMed  Google Scholar 

  85. Flohe SB, Bruggemann J, Lendemans S et al (2003) Human heat shock protein 60 induces maturation of dendritic cells versus a Th1-promoting phenotype. J Immunol 170:2340–2348. https://doi.org/10.4049/jimmunol.170.5.2340

    Article  CAS  PubMed  Google Scholar 

  86. Lorenzo N, Cantera D, Barber A et al (2015) APL-2, an altered peptide ligand derived from heat-shock protein 60, induces interleukin-10 in peripheral blood mononuclear cell derived from juvenile idiopathic arthritis patients and downregulates the inflammatory response in collagen-induced arthritis. Clin Exp Med 15:31–39. https://doi.org/10.1007/s10238-014-0273-x

    Article  CAS  PubMed  Google Scholar 

  87. Vargas-Alarcón G, Londoño JD, Hernández-Pacheco G et al (2002) Heat shock protein 70 gene polymorphisms in Mexican patients with spondyloarthropathies. Ann Rheum Dis 61:48–51

    Article  PubMed  PubMed Central  Google Scholar 

  88. Fabian TK, Csermely P, Fabian G, Fejerdy P (2009) Spondyloarthropathies and bone resorption: a possible role of heat shock protein (Hsp70). Acta Physiol Hung 96:149–155. https://doi.org/10.1556/APhysiol.96.2009.2.1

    Article  CAS  PubMed  Google Scholar 

  89. Zauner D, Quehenberger F, Hermann J et al (2014) Whole body hyperthermia treatment increases interleukin 10 and toll-like receptor 4 expression in patients with ankylosing spondylitis: a pilot study. Int J Hyperth 30:393–401. https://doi.org/10.3109/02656736.2014.956810

    Article  CAS  Google Scholar 

  90. Chen Y, Sun W, Li S et al (2015) Preliminary study of high mobility group box chromosomal protein 1(HMGB1) in ankylosing spondylitis patients. Clin Exp Rheumatol 33:187–194

    PubMed  Google Scholar 

  91. Benjamin M, Toumi H, Suzuki D et al (2009) Evidence for a distinctive pattern of bone formation in enthesophytes. Ann Rheum Dis 68:1003–1010

    Article  CAS  PubMed  Google Scholar 

  92. Pacheco-Tena C, Gonzalez-Chavez SA, Quiñones-Flores C, Burgos-Vargas R (2015) Bone proliferation in ankylosing tarsitis might involve mechanical stress, and hormonal and growth factors. J Rheumatol 42:2210–2210. https://doi.org/10.3899/jrheum.150475

    Article  CAS  PubMed  Google Scholar 

  93. Pacheco-tena C, Pérez-tamayo R, Pineda C et al (2014) Bone lineage proteins in the entheses of the midfoot in patients with spondyloarthritis. J Rheumatol 42:630–637. https://doi.org/10.3899/jrheum.140218

    Article  PubMed  Google Scholar 

  94. Xiong Z, Jiang R, Zhang P et al (2015) Transmission of ER stress response by ATF6 promotes endochondral bone growth. J Orthop Surg Res 10:141. https://doi.org/10.1186/s13018-015-0284-7

    Article  PubMed  PubMed Central  Google Scholar 

  95. Wang FS, Wu RW, Ko JY et al (2011) Heat shock protein 60 protects skeletal tissue against glucocorticoid-induced bone mass loss by regulating osteoblast survival. Bone 49:1080–1089. https://doi.org/10.1016/j.bone.2011.08.006

    Article  CAS  PubMed  Google Scholar 

  96. Pei W, Tanaka K, Huang SC et al (2016) Extracellular HSP60 triggers tissue regeneration and wound healing by regulating inflammation and cell proliferation. Npj Regen Med 1:16013. https://doi.org/10.1038/npjregenmed.2016.13

    Article  PubMed  PubMed Central  Google Scholar 

  97. Navid F, Colbert RA (2016) Causes and consequences of endoplasmic reticulum stress in rheumatic disease. Nat Rev Rheumatol. https://doi.org/10.1038/nrrheum.2016.192

    Article  PubMed  Google Scholar 

  98. Robinson PC, Brown MA (2015) ERAP2 is associated with ankylosing spondylitis in HLA-B27 -positive and HLA-B27- negative patients. Ann Rheum Dis 0:9–12. https://doi.org/10.1136/annrheumdis-2015-207416

    Article  CAS  Google Scholar 

  99. Spierings J, van Eden W (2017) Heat shock proteins and their immunomodulatory role in inflammatory arthritis. Rheumatology 56:198–208. https://doi.org/10.1093/rheumatology/kew266

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by the “Consejo Nacional de Ciencia y Tecnología”, José Pablo Romero-López received scholarships from “Consejo Nacional de Ciencia y Tecnología”, and “Beca de Estímulo Institucional de Fomento para Investigadores” from “Instituto Politécnico Nacional”. Ethel García-Latorre, and María Lilia Domínguez-López receive grants from “Comisión de Operación y Fomento de Actividades Académicas”, “Estimulo al Desempeño de Investigadores” of Instituto Politécnico Nacional”, Ethel García-Latorre, Rubén Burgos-Vargas and María Lilia Domínguez López receive a grant from “Sistema Nacional de Investigadores”. We thank Julia Moreno Manjón for her critical review and help with figures. The figures were done using icons taken from https://smart.servier.com/.

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Authors and Affiliations

  1. Laboratorio de Inmunoquímica I, Departmento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación Manuel Carpio y Plan de Ayala SN, CP 11340, Ciudad de México, México

    José Pablo Romero-López, María Lilia Domínguez-López & Ethel García-Latorre

  2. Departamento de Reumatología, Hospital General de México “Dr. Eduardo Liceaga”, Ciudad de México, México

    Rubén Burgos-Vargas

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  1. José Pablo Romero-López
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  2. María Lilia Domínguez-López
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  3. Rubén Burgos-Vargas
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  4. Ethel García-Latorre
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Contributions

All the author contributed equally to the review process. JPRL and MLDL designed the figures. EGL and RBV worked in the organization, scheming and final structure of the manuscript.

Corresponding author

Correspondence to Ethel García-Latorre.

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Romero-López, J.P., Domínguez-López, M.L., Burgos-Vargas, R. et al. Stress proteins in the pathogenesis of spondyloarthritis. Rheumatol Int 39, 595–604 (2019). https://doi.org/10.1007/s00296-018-4070-9

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  • DOI: https://doi.org/10.1007/s00296-018-4070-9

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