Cutaneous lupus erythematosus: Clinical aspects and molecular pathogenesis

Journal of Internal Medicine

Volumn 273, Issue 6, 2013, Pages 544-554

  Oke, V ^a   Wahren Herlenius, M ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Autoimmunity; Cutaneous lupus erythematosus; Ro52; Systemic lupus erythematosus; Ultraviolet radiation

Indexed keywords

AUTOANTIGEN; HIGH MOBILITY GROUP B1 PROTEIN; INTERLEUKIN 17; INTERLEUKIN 18; INTERLEUKIN 1BETA; RO ANTIBODY; RO52 AUTOANTIGEN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DERMIS; GENE LOCUS; HISTOPATHOLOGY; HUMAN; IMMUNE SYSTEM; NONHUMAN; PHENOTYPE; PHOTOSENSITIVITY; PRIORITY JOURNAL; REVIEW; SKIN LUPUS ERYTHEMATOSUS;

ANIMALS; AUTOANTIBODIES; AUTOANTIGENS; AUTOIMMUNITY; HUMANS; KERATINOCYTES; LUPUS ERYTHEMATOSUS, CUTANEOUS; SKIN;

EID: 84877926859     PISSN: 09546820     EISSN: 13652796     Source Type: Journal    
DOI: 10.1111/joim.12057     Document Type: Review

References (91)

1. Klippel JH, Stone JH, Crofford Le J, White PH, eds. Primer on The Rheumatic Diseases, 13th edn. New York: Springer, 2008; 303-38.
2. Lee HJ, Sinha AA. Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies. Autoimmunity 2006; 39: 433-44.
3. Gilliam JN, Sontheimer RD. Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 1981; 4: 471-5.
4. Kuhn A, Lehmann P, Ruzicka T. Cutaneous Lupus Erythematosus, Heidelberg: Springer-Verlag, 2005.
5. Kuhn A, Bein D, Bonsmann G. The 100th anniversary of lupus erythematosus tumidus. Autoimmun Rev 2009; 8: 441-8.
6. Albrecht J, Berlin JA, Braverman IM et al. Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus 2004; 13: 839-49.
7. Vera-Recabarren MA, Garcia-Carrasco M, Ramos-Casals M, Herrero C. Comparative analysis of subacute cutaneous lupus erythematosus and chronic cutaneous lupus erythematosus: clinical and immunological study of 270 patients. Br J Dermatol 2010; 162: 91-101.
8. Koskenmies S, Jarvinen TM, Onkamo P et al. Clinical and laboratory characteristics of Finnish lupus erythematosus patients with cutaneous manifestations. Lupus 2008; 17: 337-47.
9. Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ. Fitzpatrick's Dermatology in General Medicine, in chapter 156: Lupus Erythematosus: The McGraw-Hill Companies, 2011. http://www.accessmedicine.com/content.aspx?aID=2991998 [accessed 10 June 2012].
10. Gronhagen CM, Gunnarsson I, Svenungsson E, Nyberg F. Cutaneous manifestations and serological findings in 260 patients with systemic lupus erythematosus. Lupus 2010; 19: 1187-94.
11. Sontheimer RD. Subacute cutaneous lupus erythematosus: 25-year evolution of a prototypic subset (subphenotype) of lupus erythematosus defined by characteristic cutaneous, pathological, immunological, and genetic findings. Autoimmun Rev 2005; 4: 253-63.
12. Kuhn A, Sonntag M, Richter-Hintz D et al. Phototesting in lupus erythematosus: a 15-year experience. J Am Acad Dermatol 2001; 45: 86-95.
13. Sontheimer RD, Maddison PJ, Reichlin M, Jordon RE, Stastny P, Gilliam JN. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 1982; 97: 664-71.
14. Provost TT. Lupus band test. Int J Dermatol 1981; 20: 475-81.
15. Dahl MV. Usefulness of direct immunofluorescence in patients with lupus erythematosus. Arch Dermatol 1983; 119: 1010-7.
16. Jimenez S, Cervera R, Font J, Ingelmo M. The epidemiology of systemic lupus erythematosus. Clin Rev Allergy Immunol 2003; 25: 3-12.
17. Ben-Chetrit E, Chan EK, Sullivan KF, Tan EM. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med 1988; 167: 1560-71.
18. Chan EK, Hamel JC, Buyon JP, Tan EM. Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen. J Clin Invest 1991; 87: 68-76.
19. Itoh K, Itoh Y, Frank MB. Protein heterogeneity in the human Ro/SSA ribonucleoproteins. The 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes. J Clin Invest 1991; 87: 177-86.
20. Montano-Loza AJ, Shums Z, Norman GL, Czaja AJ. Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis. Liver Int 2011; 32: 85-92.
21. Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senecal JL. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther 2007; 9: R78.
22. Salomonsson S, Dzikaite V, Zeffer E et al. A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block. Scand J Immunol 2011; 74: 511-7.
23. Popovic K, Brauner S, Ek M, Wahren-Herlenius M, Nyberg F. Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun. Lupus 2007; 16: 10-7.
24. Popovic K, Wahren-Herlenius M, Nyberg F. Clinical follow-up of 102 anti-Ro/SSA-positive patients with dermatological manifestations. Acta Derm Venereol 2008; 88: 370-5.
25. Eriksson C, Kokkonen H, Johansson M, Hallmans G, Wadell G, Rantapaa-Dahlqvist S. Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden. Arthritis Res Ther 2011; 13: R30.
26. Rhodes B, Vyse TJ. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatology (Oxford) 2008; 47: 1603-11.
27. Lipsker D, Hauptmann G. Cutaneous manifestations of complement deficiencies. Lupus 2010; 19: 1096-106.
28. Sanchez E, Nadig A, Richardson BC et al. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. Ann Rheum Dis 2011; 70: 1752-7.
29. Jarvinen TM, Hellquist A, Koskenmies S et al. Tyrosine kinase 2 and interferon regulatory factor 5 polymorphisms are associated with discoid and subacute cutaneous lupus erythematosus. Exp Dermatol 2010; 19: 123-31.
30. Jarvinen TM, Hellquist A, Koskenmies S et al. Polymorphisms of the ITGAM gene confer higher risk of discoid cutaneous than of systemic lupus erythematosus. PLoS ONE 2010; 5: e14212.
31. Nakken B, Jonsson R, Bolstad AI. Polymorphisms of the Ro52 gene associated with anti-Ro 52-kd autoantibodies in patients with primary Sjogren's syndrome. Arthritis Rheum 2001; 44: 638-46.
32. Frank MB, Itoh K, Fujisaku A, Pontarotti P, Mattei MG, Neas BR. The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms. Am J Hum Genet 1993; 52: 183-91.
33. Sontheimer RD, Henderson CL, Grau RH. Drug-induced subacute cutaneous lupus erythematosus: a paradigm for bedside-to-bench patient-oriented translational clinical investigation. Arch Dermatol Res 2009; 301: 65-70.
34. Boeckler P, Milea M, Meyer A et al. The combination of complement deficiency and cigarette smoking as risk factor for cutaneous lupus erythematosus in men; a focus on combined C2/C4 deficiency. Br J Dermatol 2005; 152: 265-70.
35. Kuhn A, Wozniacka A, Szepietowski J et al. Photoprovocation in Cutaneous Lupus Erythematosus: a Multicenter Study Evaluating a Standardized Protocol. J Invest Dermatol 2011; 131: 1622-30.
36. Tan EM, Cohen AS, Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982; 25: 1271-7.
37. Kuhn A, Wozniacka A, Szepietowski JC et al. Photoprovocation in cutaneous lupus erythematosus: a multicenter study evaluating a standardized protocol. J Invest Dermatol 2011; 131: 1622-30.
38. Popovic K, Ek M, Espinosa A et al. Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus. Arthritis Rheum 2005; 52: 3639-45.
39. Wittmann M, Macdonald A, Renne J. IL-18 and skin inflammation. Autoimmun Rev 2009; 9: 45-8.
40. Tanasescu C, Balanescu E, Balanescu P et al. IL-17 in cutaneous lupus erythematosus. Eur J Intern Med 2010; 21: 202-7.
41. Zahn S, Rehkamper C, Kummerer BM et al. Evidence for a pathophysiological role of keratinocyte-derived type III interferon (IFNlambda) in cutaneous lupus erythematosus. J Invest Dermatol 2011; 131: 133-40.
42. Maverakis E, Miyamura Y, Bowen MP, Correa G, Ono Y, Goodarzi H. Light, including ultraviolet. J Autoimmun 2010; 34: J247-57.
43. Bennion SD, Norris DA. Ultraviolet light modulation of autoantigens, epidermal cytokines and adhesion molecules as contributing factors of the pathogenesis of cutaneous LE. Lupus 1997; 6: 181-92.
44. Reefman E, Kuiper H, Limburg PC, Kallenberg CG, Bijl M. Type I interferons are involved in the development of ultraviolet B-induced inflammatory skin lesions in systemic lupus erythaematosus patients. Ann Rheum Dis 2008; 67: 11-18.
45. Loetscher M, Gerber B, Loetscher P et al. Chemokine receptor specific for IP10 and mig: structure, function, and expression in activated T-lymphocytes. J Exp Med 1996; 184: 963-9.
46. Flier J, Boorsma DM, van Beek PJ et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol 2001; 194: 398-405.
47. Meller S, Winterberg F, Gilliet M et al. Ultraviolet radiation-induced injury, chemokines, and leukocyte recruitment: an amplification cycle triggering cutaneous lupus erythematosus. Arthritis Rheum 2005; 52: 1504-16.
48. Wenzel J, Zahn S, Mikus S, Wiechert A, Bieber T, Tuting T. The expression pattern of interferon-inducible proteins reflects the characteristic histological distribution of infiltrating immune cells in different cutaneous lupus erythematosus subsets. Br J Dermatol 2007; 157: 752-7.
49. Kabashima K, Shiraishi N, Sugita K et al. CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells. Am J Pathol 2007; 171: 1249-57.
50. Lacotte S, Brun S, Muller S, Dumortier H. CXCR3, inflammation, and autoimmune diseases. Ann N Y Acad Sci 2009; 1173: 310-7.
51. Blomberg S, Eloranta ML, Cederblad B, Nordlin K, Alm GV, Ronnblom L. Presence of cutaneous interferon-alpha producing cells in patients with systemic lupus erythematosus. Lupus 2001; 10: 484-90.
52. Farkas L, Beiske K, Lund-Johansen F, Brandtzaeg P, Jahnsen FL. Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. Am J Pathol 2001; 159: 237-43.
53. Ronnblom L, Alm GV, Eloranta ML. Type I interferon and lupus. Curr Opin Rheumatol 2009; 21: 471-7.
54. Witte K, Gruetz G, Volk HD et al. Despite IFN-lambda receptor expression, blood immune cells, but not keratinocytes or melanocytes, have an impaired response to type III interferons: implications for therapeutic applications of these cytokines. Genes Immun 2009; 10: 702-14.
55. Kuhn A, Herrmann M, Kleber S et al. Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation. Arthritis Rheum 2006; 54: 939-50.
56. Munoz LE, Lauber K, Schiller M, Manfredi AA, Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010; 6: 280-9.
57. Cals-Grierson MM, Ormerod AD. Nitric oxide function in the skin. Nitric Oxide 2004; 10: 179-93.
58. Kuhn A, Fehsel K, Lehmann P, Krutmann J, Ruzicka T, Kolb-Bachofen V. Aberrant timing in epidermal expression of inducible nitric oxide synthase after UV irradiation in cutaneous lupus erythematosus. J Invest Dermatol 1998; 111: 149-53.
59. Casciola-Rosen L, Rosen A. Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE. Lupus 1997; 6: 175-80.
60. Saegusa J, Kawano S, Koshiba M et al. Oxidative stress mediates cell surface expression of SS-A/Ro antigen on keratinocytes. Free Radic Biol Med 2002; 32: 1006-16.
61. Lawley W, Doherty A, Denniss S et al. Rapid lupus autoantigen relocalization and reactive oxygen species accumulation following ultraviolet irradiation of human keratinocytes. Rheumatology (Oxford) 2000; 39: 253-61.
62. Nobuhara Y, Kawano S, Kageyama G, Sugiyama D, Saegusa J, Kumagai S. Is SS-A/Ro52 a hydrogen peroxide-sensitive signaling molecule? Antioxid Redox Signal 2007; 9: 385-91.
63. Barkauskaite V, Ek M, Popovic K, Harris HE, Wahren-Herlenius M, Nyberg F. Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus. Lupus 2007; 16: 794-802.
64. Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002; 418: 191-5.
65. Andersson UG, Tracey KJ. HMGB1, a pro-inflammatory cytokine of clinical interest: introduction. J Intern Med 2004; 255: 318-9.
66. Urbonaviciute V, Furnrohr BG, Meister S et al. Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med 2008; 205: 3007-18.
67. Reymond A, Meroni G, Fantozzi A et al. The tripartite motif family identifies cell compartments. EMBO J 2001; 20: 2140-51.
68. Espinosa A, Zhou W, Ek M et al. The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death. J Immunol 2006; 176: 6277-85.
69. Kong HJ, Anderson DE, Lee CH et al. Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J Immunol 2007; 179: 26-30.
70. Higgs R, Ni Gabhann J, Ben Larbi N, Breen EP, Fitzgerald KA, Jefferies CA. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J Immunol 2008; 181: 1780-6.
71. Higgs R, Lazzari E, Wynne C et al. Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors. PLoS ONE 2010; 5: e11776.
72. Espinosa A, Dardalhon V, Brauner S et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med 2009; 206: 1661-71.
73. Ishii T, Ohnuma K, Murakami A et al. SS-A/Ro52, an autoantigen involved in CD28-mediated IL-2 production. J Immunol 2003; 170: 3653-61.
74. Yang K, Shi HX, Liu XY et al. TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response. J Immunol 2009; 182: 3782-92.
75. Strandberg L, Ambrosi A, Espinosa A et al. Interferon-alpha induces up-regulation and nuclear translocation of the Ro52 autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies. J Clin Immunol 2008; 28: 220-31.
76. Rhodes DA, Ihrke G, Reinicke AT et al. The 52 000 MW Ro/SS-A autoantigen in Sjogren's syndrome/systemic lupus erythematosus (Ro52) is an interferon-gamma inducible tripartite motif protein associated with membrane proximal structures. Immunology 2002; 106: 246-56.
77. Oke V, Vassilaki I, Espinosa A et al. High Ro52 expression in spontaneous and UV-induced cutaneous inflammation. J Invest Dermatol 2009; 129: 2000-10.
78. Espinosa A, Hennig J, Ambrosi A et al. Anti-Ro52 autoantibodies from patients with Sjogren's syndrome inhibit the Ro52 E3 ligase activity by blocking the E3/E2 interface. J Biol Chem 2011; 286: 36478-91.
79. Graham RR, Kozyrev SV, Baechler EC et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006; 38: 550-5.
80. Fu Q, Zhao J, Qian X et al. Association of a functional IRF7 variant with systemic lupus erythematosus. Arthritis Rheum 2011; 63: 749-54.
81. Keeble AH, Khan Z, Forster A, James LC. TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved. Proc Natl Acad Sci U S A 2008; 105: 6045-50.
82. Munoz LE, Janko C, Grossmayer GE et al. Remnants of secondarily necrotic cells fuel inflammation in systemic lupus erythematosus. Arthritis Rheum 2009; 60: 1733-42.
83. Lee Y, Kim H, Kim S et al. Myeloid differentiation factor 88 regulates basal and UV-induced expressions of IL-6 and MMP-1 in human epidermal keratinocytes. J Invest Dermatol 2009; 129: 460-7.
84. Abbas AK. Cellular and Molecular Immunology, 6th ed. Philadelphia: Saunders Elsevier, 2007.
85. Tian J, Avalos AM, Mao SY et al. Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 2007; 8: 487-96.
86. Yoshimi R, Ishigatsubo Y, Ozato K. Autoantigen TRIM21/Ro52 as a Possible Target for Treatment of Systemic Lupus Erythematosus. Int J Rheumatol 2012; 2012: 718237.
87. Yoshimi R, Chang TH, Wang H, Atsumi T, Morse HC 3rd, Ozato K. Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts. J Immunol 2009; 182: 7527-38.
88. Kuhn A, Lehmann P, Ruzicka T. Cutaneous Lupus Erythematosus. Heidelberg: Springer-Verlag Berlin, 2005.
89. Werth VP, Callen JP, Ang G, Sullivan KE. Associations of tumor necrosis factor alpha and HLA polymorphisms with adult dermatomyositis: implications for a unique pathogenesis. J Invest Dermatol 2002; 119: 617-20.
90. Shapiro M, Sosis AC, Junkins-Hopkins JM, Werth VP. Lupus erythematosus induced by medications, ultraviolet radiation, and other exogenous agents: a review, with special focus on the development of subacute cutaneous lupus erythematosus in a genetically predisposed individual. Int J Dermatol 2004; 43: 87-94.
91. Namjou B, Kothari PH, Kelly JA et al. Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort. Genes Immun 2011; 12: 270-9.