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Heat Shock Proteins as Target Autoantigens in Autoimmune Rheumatic Diseases

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Heat Shock Proteins in Inflammatory Diseases

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Abbreviations

ACPA:

anti-citrullinated peptide antibodies

AECA:

anti-endothelial cell antibodies

aPL:

anti-phospholipid

autoabs:

autoantibodies

BD:

Behçet’s disease

BiP:

immunoglobulin heavy-chain-binding protein

CCP:

cyclic citrullinated peptide

Hsp:

heat shock protein(s)

IL:

interleukin

ILD:

interstitial lung disease

PAH:

pulmonary arterial hypertension

RA:

rheumatoid arthritis

SjS:

Sjogren’s syndrome

SLE:

Systemic lupus erythematosus

SSc:

systemic sclerosis

TNF-α:

tumor necrosis factor α

References

  1. Alard JE, Hillion S, Guillevin L et al (2011) Autoantibodies to endothelial cell surface ATP synthase, the endogenous receptor for hsp60, might play a pathogenic role in vasculatides. PLoS One 6:e14654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Al-Hashimi AA, Caldwell J, Gonzalez-Gronow M et al (2010) Binding of anti-GRP78 autoantibodies to cell surface GRP78 increases tissue factor procoagulant activity via the release of calcium from endoplasmic reticulum stores. J Biol Chem 285:28912–28923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Baird NA, Turnbull DW, Johnson EA (2006) Induction of the heat shock pathway during hypoxia requires regulation of heat shock factor by hypoxia-inducible factor-1. J Biol Chem 281:38675–38681

    Article  CAS  PubMed  Google Scholar 

  4. Baroni SS, Santillo M, Bevilacqua F et al (2006) Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med 354:2667–2676

    Article  CAS  PubMed  Google Scholar 

  5. Birtas-Atesoglu E, Inanc N, Yavuz S, Ergun T, Direskeneli H (2008) Serum levels of free heat shock protein 70 and anti-HSP70 are elevated in Behcet’s disease. Clin Exp Rheumatol 26:S96–S98

    CAS  PubMed  Google Scholar 

  6. Blass S, Union A, Raymackers J et al (2001) The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis. Arthritis Rheum 44:761–771

    Article  CAS  PubMed  Google Scholar 

  7. Bodman-Smith MD, Corrigall VM, Berglin E et al (2004) Antibody response to the human stress protein BiP in rheumatoid arthritis. Rheumatology 43:1283–1287

    Article  CAS  PubMed  Google Scholar 

  8. Boehm J, Orth T, Van Nguyen P, Soling HD (1994) Systemic lupus erythematosus is associated with increased auto-antibody titers against calreticulin and grp94, but calreticulin is not the Ro/SS-A antigen. Eur J Clin Investig 24:248–257

    Article  CAS  Google Scholar 

  9. Cao Y, Ohwatari N, Matsumoto T, Kosaka M, Ohtsuru A, Yamashita S (1999) TGF-beta1 mediates 70-kDa heat shock protein induction due to ultraviolet irradiation in human skin fibroblasts. Pflugers Archiv Eur J Physiol 438:239–244

    Article  CAS  Google Scholar 

  10. Celet B, Akman-Demir G, Serdaroglu P et al (2000) Anti-alpha B-crystallin immunoreactivity in inflammatory nervous system diseases. J Neurol 247:935–939

    Article  CAS  PubMed  Google Scholar 

  11. Chen P, Shi L, Jiang Y et al (2015) Identification of heat shock protein 27 as a novel autoantigen of Behcet’s disease. Biochem Biophys Res Commun 456:866–871

    Article  CAS  PubMed  Google Scholar 

  12. Cheng MY, Hartl FU, Horwich AL (1990) The mitochondrial chaperonin hsp60 is required for its own assembly. Nature 348:455–458

    Article  CAS  PubMed  Google Scholar 

  13. Chizzolini C, Raschi E, Rezzonico R et al (2002) Autoantibodies to fibroblasts induce a proadhesive and proinflammatory fibroblast phenotype in patients with systemic sclerosis. Arthritis Rheum 46:1602–1613

    Article  CAS  PubMed  Google Scholar 

  14. Choy EH, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916

    Article  CAS  PubMed  Google Scholar 

  15. Clarke A, Perry E, Kelly C et al (2017) Heightened autoantibody immune response to citrullinated calreticulin in bronchiectasis: implications for rheumatoid arthritis. Int J Biochem Cell Biol 89:199–206

    Article  CAS  PubMed  Google Scholar 

  16. Conroy SE, Faulds GB, Williams W, Latchman DS, Isenberg DA (1994) Detection of autoantibodies to the 90 kDa heat shock protein in systemic lupus erythematosus and other autoimmune diseases. Br J Rheumatol 33:923–926

    Article  CAS  PubMed  Google Scholar 

  17. Corrigall VM, Bodman-Smith MD, Fife MS et al (2001) The human endoplasmic reticulum molecular chaperone BiP is an autoantigen for rheumatoid arthritis and prevents the induction of experimental arthritis. J Immunol 166:1492–1498

    Article  CAS  PubMed  Google Scholar 

  18. Daugaard M, Rohde M, Jaattela M (2007) The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett 581:3702–3710

    Article  CAS  PubMed  Google Scholar 

  19. de Graeff-Meeder ER, Rijkers GT, Voorhorst-Ogink MM et al (1993) Antibodies to human HSP60 in patients with juvenile chronic arthritis, diabetes mellitus, and cystic fibrosis. Pediatr Res 34:424–428

    Article  PubMed  Google Scholar 

  20. de Smet MD, Ramadan A (2001) Circulating antibodies to inducible heat shock protein 70 in patients with uveitis. Ocul Immunol Inflamm 9:85–92

    Article  PubMed  Google Scholar 

  21. Dieude M, Senecal JL, Raymond Y (2004) Induction of endothelial cell apoptosis by heat-shock protein 60-reactive antibodies from anti-endothelial cell autoantibody-positive systemic lupus erythematosus patients. Arthritis Rheum 50:3221–3231

    Article  CAS  PubMed  Google Scholar 

  22. Dieude M, Correa JA, Neville C et al (2011) Association of autoantibodies to heat-shock protein 60 with arterial vascular events in patients with antiphospholipid antibodies. Arthritis Rheum 63:2416–2424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Direskeneli H, Hasan A, Shinnick T et al (1996) Recognition of B-cell epitopes of the 65 kDa HSP in Behcet’s disease. Scand J Immunol 43:464–471

    Article  CAS  PubMed  Google Scholar 

  24. Doino M, Yokoyama M, Sasaki Y, Kondo K, Yasuda Y, Arakawa S (2017) Evaluation of the relationship between salivary concentration of anti-heat shock protein immunoglobulin and clinical manifestations of Behcet’s disease. Scand J Rheumatol 46:381–387

    Article  CAS  PubMed  Google Scholar 

  25. Dulle JE, Fort PE (2016) Crystallins and neuroinflammation: the glial side of the story. Biochim Biophys Acta 1860:278–286

    Article  CAS  PubMed  Google Scholar 

  26. Eggleton P, Ward FJ, Johnson S et al (2000) Fine specificity of autoantibodies to calreticulin: epitope mapping and characterization. Clin Exp Immunol 120:384–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Faulds G, Conroy S, Madaio M, Isenberg D, Latchman D (1995) Increased levels of antibodies to heat shock proteins with increasing age in Mrl/Mp-lpr/lpr mice. Br J Rheumatol 34:610–615

    Article  CAS  PubMed  Google Scholar 

  28. Fujimoto M, Sato S, Ihn H, Takehara K (1995) Autoantibodies to the heat-shock protein hsp73 in localized scleroderma. Arch Dermatol Res 287:581–585

    Article  CAS  PubMed  Google Scholar 

  29. Fujimoto M, Hamaguchi Y, Yazawa N, Komura K, Takehara K, Sato S (2004) Autoantibodies to a collagen-specific molecular chaperone, heat-shock protein 47, in systemic sclerosis. Clin Exp Immunol 138:534–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Girouard L, Laux DC, Jindal S, Nelson DR (1993) Immune recognition of human Hsp60 by Lyme disease patient sera. Microb Pathog 14:287–297

    Article  CAS  PubMed  Google Scholar 

  31. Goeb V, Thomas-L’Otellier M, Daveau R et al (2009) Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are chaperones and citrullinated glycolytic enzymes. Arthritis Res Ther 11:R38

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Gupta RS (1990) Sequence and structural homology between a mouse T-complex protein TCP-1 and the ‘chaperonin’ family of bacterial (GroEL, 60-65 kDa heat shock antigen) and eukaryotic proteins. Biochem Int 20:833–841

    CAS  PubMed  Google Scholar 

  33. Handley HH, Yu J, Yu DT, Singh B, Gupta RS, Vaughan JH (1996) Autoantibodies to human heat shock protein (hsp)60 may be induced by Escherichia coli groEL. Clin Exp Immunol 103:429–435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Harlow L, Rosas IO, Gochuico BR et al (2013) Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthritis-associated interstitial lung disease. Arthritis Rheum 65:869–879

    Article  CAS  PubMed  Google Scholar 

  35. Harlow L, Gochuico BR, Rosas IO et al (2014) Anti-citrullinated heat shock protein 90 antibodies identified in bronchoalveolar lavage fluid are a marker of lung-specific immune responses. Clin Immunol 155:60–70

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hartl FU (1996) Molecular chaperones in cellular protein folding. Nature 381:571–579

    Article  CAS  PubMed  Google Scholar 

  37. Hirata D, Hirai I, Iwamoto M et al (1997) Preferential binding with Escherichia coli hsp60 of antibodies prevalent in sera from patients with rheumatoid arthritis. Clin Immunol Immunopathol 82:141–148

    Article  CAS  PubMed  Google Scholar 

  38. Horvath L, Czirjak L, Fekete B et al (2001) Levels of antibodies against C1q and 60 kDa family of heat shock proteins in the sera of patients with various autoimmune diseases. Immunol Lett 75:103–109

    Article  CAS  PubMed  Google Scholar 

  39. Iwaki T, Wisniewski T, Iwaki A et al (1992) Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions. Am J Pathol 140:345–356

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Jamin C, Dugue C, Alard JE et al (2005) Induction of endothelial cell apoptosis by the binding of anti-endothelial cell antibodies to Hsp60 in vasculitis-associated systemic autoimmune diseases. Arthritis Rheum 52:4028–4038

    Article  CAS  PubMed  Google Scholar 

  41. Jarjour WN, Jeffries BD, Davis JS, Welch WJ, Mimura T, Winfield JB (1991) Autoantibodies to human stress proteins. A survey of various rheumatic and other inflammatory diseases. Arthritis Rheum 34:1133–1138

    Article  CAS  PubMed  Google Scholar 

  42. Jones DB, Coulson AF, Duff GW (1993) Sequence homologies between hsp60 and autoantigens. Immunol Today 14:115–118

    Article  CAS  PubMed  Google Scholar 

  43. Jorgensen CS, Hansen KB, Jacobsen S et al (2005) Absence of high-affinity calreticulin autoantibodies in patients with systemic rheumatic diseases and coeliac disease. Scand J Clin Lab Invest 65:403–412

    Article  CAS  PubMed  Google Scholar 

  44. Kapsimali VD, Kanakis MA, Vaiopoulos GA, Kaklamanis PG (2010) Etiopathogenesis of Behcet’s disease with emphasis on the role of immunological aberrations. Clin Rheumatol 29:1211–1216

    Article  PubMed  Google Scholar 

  45. Karlsson-Parra A, Soderstrom K, Ferm M, Ivanyi J, Kiessling R, Klareskog L (1990) Presence of human 65 kD heat shock protein (hsp) in inflamed joints and subcutaneous nodules of RA patients. Scand J Immunol 31:283–288

    Article  CAS  PubMed  Google Scholar 

  46. Kaul A, Gordon C, Crow MK et al (2016) Systemic lupus erythematosus. Nat Rev Dis Primers 2:16039

    Article  PubMed  Google Scholar 

  47. Kelly M, Lihua S, Zhe Z et al (2018) Transposable element dysregulation in systemic lupus erythematosus and regulation by histone conformation and Hsp90. Clin Immunol 197:6–18

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kenderov A, Minkova V, Mihailova D et al (2002) Lupus-specific kidney deposits of HSP90 are associated with altered IgG idiotypic interactions of anti-HSP90 autoantibodies. Clin Exp Immunol 129:169–176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kilic A, Mandal K (2012) Heat shock proteins: pathogenic role in atherosclerosis and potential therapeutic implications. Autoimmune Dis 2012:502813

    PubMed  PubMed Central  Google Scholar 

  50. Kimura A, Sakurai T, Tanaka Y et al (2008) Proteomic analysis of autoantibodies in neuropsychiatric systemic lupus erythematosus patient with white matter hyperintensities on brain MRI. Lupus 17:16–20

    Article  CAS  PubMed  Google Scholar 

  51. Kimura A, Sakurai T, Yamada M et al (2012) Elevated anti-heat shock protein 60 antibody titer is related to white matter hyperintensities. J Stroke Cerebrovasc Dis 21:305–309

    Article  PubMed  Google Scholar 

  52. Kindas-Mugge I, Steiner G, Smolen JS (1993) Similar frequency of autoantibodies against 70-kD class heat-shock proteins in healthy subjects and systemic lupus erythematosus patients. Clin Exp Immunol 92:46–50

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kishore U, Sontheimer RD, Sastry KN et al (1997) The systemic lupus erythematosus (SLE) disease autoantigen-calreticulin can inhibit C1q association with immune complexes. Clin Exp Immunol 108:181–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Klemenz R, Frohli E, Steiger RH, Schafer R, Aoyama A (1991) Alpha B-crystallin is a small heat shock protein. Proc Natl Acad Sci U S A 88:3652–3656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Komiya I, Arimura Y, Nakabayashi K et al (2011) Increased concentrations of antibody against heat shock protein in patients with myeloperoxidase anti-neutrophil cytoplasmic autoantibody positive microscopic polyangiitis. Microbiol Immunol 55:531–538

    Article  CAS  PubMed  Google Scholar 

  56. Li Z, Srivastava P (2004) Heat-shock proteins. Curr Protocs Immunol Appendix 1:Appendix 1T

    Google Scholar 

  57. Lu MC, Lai NS, Yu HC, Huang HB, Hsieh SC, Yu CL (2010) Anti-citrullinated protein antibodies bind surface-expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor alpha production. Arthritis Rheum 62:1213–1223

    Article  CAS  PubMed  Google Scholar 

  58. Lu MC, Yu CL, Yu HC, Huang HB, Koo M, Lai NS (2016) Anti-citrullinated protein antibodies promote apoptosis of mature human Saos-2 osteoblasts via cell-surface binding to citrullinated heat shock protein 60. Immunobiology 221:76–83

    Article  CAS  PubMed  Google Scholar 

  59. Makhnevych T, Houry WA (2012) The role of Hsp90 in protein complex assembly. Biochim Biophys Acta 1823:674–682

    Article  CAS  PubMed  Google Scholar 

  60. Mantej J, Polasik K, Piotrowska E, Tukaj S (2019) Autoantibodies to heat shock proteins 60, 70, and 90 in patients with rheumatoid arthritis. Cell Stress Chaperones 24:283–287

    Article  CAS  PubMed  Google Scholar 

  61. Mavragani CP, Sagalovskiy I, Guo Q et al (2016) Expression of long interspersed nuclear element 1 Retroelements and induction of type I interferon in patients with systemic autoimmune disease. Arthritis Rheum 68:2686–2696

    Article  CAS  Google Scholar 

  62. McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219

    Article  CAS  PubMed  Google Scholar 

  63. Meroni PL, D’Cruz D, Khamashta M, Youinou P, Hughes GR (1996) Anti-endothelial cell antibodies: only for scientists or for clinicians too? Clin Exp Immunol 104:199–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Minota S, Cameron B, Welch WJ, Winfield JB (1988a) Autoantibodies to the constitutive 73-kD member of the hsp70 family of heat shock proteins in systemic lupus erythematosus. J Exp Med 168:1475–1480

    Article  CAS  PubMed  Google Scholar 

  65. Minota S, Koyasu S, Yahara I, Winfield J (1988b) Autoantibodies to the heat-shock protein hsp90 in systemic lupus erythematosus. J Clin Invest 81:106–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Mosca M, Tani C, Vagnani S, Carli L, Bombardieri S (2014) The diagnosis and classification of undifferentiated connective tissue diseases. J Autoimmun 48–49:50–52

    Article  PubMed  Google Scholar 

  67. Munroe ME, Lu R, Zhao YD et al (2016) Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification. Ann Rheum Dis 75:2014–2021

    Article  CAS  PubMed  Google Scholar 

  68. Neuhaus-Steinmetz U, Rensing L (1997) Heat shock protein induction by certain chemical stressors is correlated with their cytotoxicity, lipophilicity and protein-denaturing capacity. Toxicology 123:185–195

    Article  CAS  PubMed  Google Scholar 

  69. Panayi GS, Corrigall VM (2014) Immunoglobulin heavy-chain-binding protein (BiP): a stress protein that has the potential to be a novel therapy for rheumatoid arthritis. Biochem Soc Trans 42:1752–1755

    Article  CAS  PubMed  Google Scholar 

  70. Pathak JL, Bakker AD, Verschueren P et al (2015) CXCL8 and CCL20 enhance Osteoclastogenesis via modulation of cytokine production by human primary osteoblasts. PLoS One 10:e0131041

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  71. Pereira I, Laurindo I, Burlingame R et al (2008) Auto-antibodies do not influence development of atherosclerotic plaques in rheumatoid arthritis. Joint Bone Spine 75:416–421

    Article  CAS  PubMed  Google Scholar 

  72. Pervin K, Childerstone A, Shinnick T et al (1993) T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behcet’s disease. J Immunol 151:2273–2282

    CAS  PubMed  Google Scholar 

  73. Renaudineau Y, Dugue C, Dueymes M, Youinou P (2002) Antiendothelial cell antibodies in systemic lupus erythematosus. Autoimmun Rev 1:365–372

    Article  CAS  PubMed  Google Scholar 

  74. Rokeach LA, Haselby JA, Meilof JF et al (1991) Characterization of the autoantigen calreticulin. J Immunol 147:3031–3039

    CAS  PubMed  Google Scholar 

  75. Routsias JG, Tzioufas AG, Sakarellos-Daitsiotis M, Sakarellos C, Moutsopoulos HM (1993) Calreticulin synthetic peptide analogues: anti-peptide antibodies in autoimmune rheumatic diseases. Clin Exp Immunol 91:437–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Rudolphi U, Rzepka R, Batsford S et al (1997) The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat-shock protein 60 or human type II collagen in synovial fluid and tissue. Arthritis Rheum 40:1409–1419

    Article  CAS  PubMed  Google Scholar 

  77. Sakkas LI, Bogdanos DP (2016) The role of B cells in the pathogenesis of systemic sclerosis. Isr Med Assoc J 18:516–519

    PubMed  Google Scholar 

  78. Sakkas LI, Bogdanos DP, Katsiari C, Platsoucas CD (2014) Anti-citrullinated peptides as autoantigens in rheumatoid arthritis-relevance to treatment. Autoimmun Rev 13:1114–1120

    Article  CAS  PubMed  Google Scholar 

  79. Sanchez D, Tuckova L, Sebo P et al (2000) Occurrence of IgA and IgG autoantibodies to calreticulin in coeliac disease and various autoimmune diseases. J Autoimmun 15:441–449

    Article  CAS  PubMed  Google Scholar 

  80. Shaker O, Ay El-Deen MA, El Hadidi H, Grace BD, El Sherif H, Abdel Halim A (2007) The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behcet disease. Br J Dermatol 156:32–37

    Article  CAS  PubMed  Google Scholar 

  81. Shoda H, Fujio K, Shibuya M et al (2011) Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis. Arthritis Res Ther 13:R191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Shoda H, Hanata N, Sumitomo S, Okamura T, Fujio K, Yamamoto K (2016) Immune responses to Mycobacterial heat shock protein 70 accompany self-reactivity to human BiP in rheumatoid arthritis. Sci Rep 6:22486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shovman O, Sherer Y, Gilbourd B et al (2005) Low levels of heat shock proteins-60 and -65 autoantibodies in Sjogren’s syndrome. Isr Med Assoc J 7:778–780

    CAS  PubMed  Google Scholar 

  84. Stephanou A, Conroy S, Isenberg DA et al (1998) Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (hsp90) and the production of anti-hsp90 antibodies. J Autoimmun 11:249–253

    Article  CAS  PubMed  Google Scholar 

  85. Tamby MC, Humbert M, Guilpain P et al (2006) Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur Respir J 28:799–807

    Article  CAS  PubMed  Google Scholar 

  86. Tasab M, Batten MR, Bulleid NJ (2000) Hsp47: a molecular chaperone that interacts with and stabilizes correctly-folded procollagen. EMBO J 19:2204–2211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Terrier B, Tamby MC, Camoin L et al (2008) Identification of target antigens of antifibroblast antibodies in pulmonary arterial hypertension. Am J Respir Crit Care Med 177:1128–1134

    Article  CAS  PubMed  Google Scholar 

  88. Tong L, Koh V, Thong BY (2017) Review of autoantigens in Sjogren’s syndrome: an update. J Inflamm Res 10:97–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Trautinger F, Trautinger I, Kindas-Mugge I, Metze D, Luger TA (1993) Human keratinocytes in vivo and in vitro constitutively express the 72-kD heat shock protein. J Invest Dermatol 101:334–338

    Article  CAS  PubMed  Google Scholar 

  90. Travers TS, Harlow L, Rosas IO et al (2016) Extensive citrullination promotes immunogenicity of HSP90 through protein unfolding and exposure of cryptic epitopes. J Immunol 197:1926–1936

    Article  CAS  PubMed  Google Scholar 

  91. van Eden W, Jansen MAA, Ludwig I, van Kooten P, van der Zee R, Broere F (2017) The enigma of heat shock proteins in immune tolerance. Front Immunol 8:1599

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. van Halm VP, Slot MC, Nurmohamed MT, Tervaert JW, Dijkmans BA, Voskuyl AE (2006) Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis. Ann Rheum Dis 65:590–594

    Article  PubMed  CAS  Google Scholar 

  93. van Paassen P, Duijvestijn A, Debrus-Palmans L, Damoiseaux J, Vroomen M, Tervaert JW (2007) Induction of endothelial cell apoptosis by IgG antibodies from SLE patients with nephropathy: a potential role for anti-endothelial cell antibodies. Ann N Y Acad Sci 1108:147–156

    Article  PubMed  CAS  Google Scholar 

  94. Vidyasagar A, Wilson NA, Djamali A (2012) Heat shock protein 27 (HSP27): biomarker of disease and therapeutic target. Fibrogenesis Tissue Repair 5:7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Weber CK, Haslbeck M, Englbrecht M et al (2010) Antibodies to the endoplasmic reticulum-resident chaperones calnexin, BiP and Grp94 in patients with rheumatoid arthritis and systemic lupus erythematosus. Rheumatology 49:2255–2263

    Article  CAS  PubMed  Google Scholar 

  96. Wick G, Knoflach M, Xu Q (2004) Autoimmune and inflammatory mechanisms in atherosclerosis. Annu Rev Immunol 22:361–403

    Article  CAS  PubMed  Google Scholar 

  97. Yokota S, Fujii N (2010) Immunomodulatory activity of extracellular heat shock proteins and their autoantibodies. Microbiol Immunol 54:299–307

    CAS  PubMed  Google Scholar 

  98. Yokota SI, Hirata D, Minota S et al (2000) Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins. Cell Stress Chaperones 5:337–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Yokota S, Minota S, Fujii N (2006) Anti-HSP auto-antibodies enhance HSP-induced pro-inflammatory cytokine production in human monocytic cells via toll-like receptors. Int Immunol 18:573–580

    Article  CAS  PubMed  Google Scholar 

  100. Yu HC, Lai PH, Lai NS, Huang HB, Koo M, Lu MC (2016) Increased serum levels of anti-carbamylated 78-kDa glucose-regulated protein antibody in patients with rheumatoid arthritis. Int J Mol Sci 17:1510

    Article  PubMed Central  CAS  Google Scholar 

  101. Zampieri S, Iaccarino L, Ghirardello A et al (2005) Systemic lupus erythematosus, atherosclerosis, and autoantibodies. Ann N Y Acad Sci 1051:351–361

    Article  CAS  PubMed  Google Scholar 

  102. Zeidan MJ, Saadoun D, Garrido M, Klatzmann D, Six A, Cacoub P (2016) Behcet’s disease physiopathology: a contemporary review. Autoimmun Highlights 7:4

    Article  CAS  Google Scholar 

  103. Zhou X, Tan FK, Milewicz DM, Guo X, Bona CA, Arnett FC (2005) Autoantibodies to fibrillin-1 activate normal human fibroblasts in culture through the TGF-beta pathway to recapitulate the “scleroderma phenotype”. J Immunol 175:4555–4560

    Article  CAS  PubMed  Google Scholar 

  104. Zhu J, Quyyumi AA, Rott D et al (2001) Antibodies to human heat-shock protein 60 are associated with the presence and severity of coronary artery disease: evidence for an autoimmune component of atherogenesis. Circulation 103:1071–1075

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

G.E. is supported by a PhD scholarship funded by the Hellenic Scholarship Foundation (IKY, Greece). L.I.S. received lecture honoraria from Actelion, Janssen, Novartis, Sanofi Aventis, Abbvie and Roche and a grant from Bristol Meyers Squib to support the educational and research activities of the department. None of this funding relates to the scientific content of this chapter. D.P.B. received lecture honoraria/advisory board participation from Novartis, Fresenius Kabi and Roche and grants from Genesis, Aenorasis and Elpen to support the educational and research activities of the department.

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Efthymiou, G., Sakkas, L.I., Bogdanos, D.P. (2021). Heat Shock Proteins as Target Autoantigens in Autoimmune Rheumatic Diseases. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Inflammatory Diseases. Heat Shock Proteins, vol 22. Springer, Cham. https://doi.org/10.1007/7515_2020_35

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