Lupus erythematosus revisited

Seminars in Immunopathology

Volumn 38, Issue 1, 2016, Pages 97-112

  Kuhn, Annegret ^a,b   Wenzel, Joerg ^c   Bijl, Marc ^d  

^a UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c UNIVERSITY HOSPITAL BONN   (Germany)

^d MARTINI HOSPITAL   (Netherlands)

Author keywords

Apoptosis; Cutaneous lupus erythematosus; Interferons; Necrosis; Pathogenesis; Photoprovocation; Photosensitivity; Systemic lupus erythematosus; UV light

Indexed keywords

AUTOANTIBODY; INTERFERON; HIGH MOBILITY GROUP B1 PROTEIN;

ADAPTIVE IMMUNITY; ANTIGEN ANTIBODY COMPLEX; APOPTOSIS; CELL DEATH; CHILBLAIN LUPUS ERYTHEMATOSUS; CLINICAL FEATURE; DISCOID LUPUS ERYTHEMATOSUS; DISEASE CLASSIFICATION; DISEASE SEVERITY; ENVIRONMENTAL FACTOR; GENETIC PREDISPOSITION; HISTOPATHOLOGY; HUMAN; IMMUNOPATHOLOGY; INNATE IMMUNITY; LUPUS ERYTHEMATOSUS; LUPUS ERYTHEMATOSUS PANNICULITIS; LUPUS ERYTHEMATOSUS TUMIDUS; NONHUMAN; PATHOGENESIS; PHOTOSENSITIVITY; PRIORITY JOURNAL; PROVOCATION TEST; REVIEW; SKIN LUPUS ERYTHEMATOSUS; ULTRAVIOLET RADIATION; ADVERSE EFFECTS; ANIMAL; COMPLICATION; GENETICS; IMMUNOLOGY; LUPUS ERYTHEMATOSUS, CUTANEOUS; LUPUS ERYTHEMATOSUS, SYSTEMIC; METABOLISM; PATHOLOGY; PHOTOSENSITIVITY DISORDER; SKIN;

ANIMALS; CELL DEATH; HMGB1 PROTEIN; HUMANS; INTERFERONS; LUPUS ERYTHEMATOSUS, CUTANEOUS; LUPUS ERYTHEMATOSUS, SYSTEMIC; PHOTOSENSITIVITY DISORDERS; SKIN; ULTRAVIOLET RAYS;

EID: 84953637386     PISSN: 18632297     EISSN: 18632300     Source Type: Journal    
DOI: 10.1007/s00281-015-0550-0     Document Type: Review

References (168)

1. Avihingsanon Y, Hirankarn N (2010) Major lupus organ involvement: severe lupus nephritis. Lupus 19:1391–1398. doi:10.1177/0961203310376522
2. Kuhn A, Bonsmann G, Anders HJ, Herzer P, Tenbrock K, Schneider M (2015) The diagnosis and treatment of systemic lupus erythematosus. Dtsch Arztebl Int 112:423–432. doi:10.3238/arztebl.2015.0423
3. Naleway AL, Davis ME, Greenlee RT, Wilson DA, McCarty DJ (2005) Epidemiology of systemic lupus erythematosus in rural Wisconsin. Lupus 14:862–866. doi:10.1191/0961203305lu2182xx
4. Uramoto KM, Michet CJ Jr, Thumboo J, Sunku J, O’Fallon WM, Gabriel SE (1999) Trends in the incidence and mortality of systemic lupus erythematosus, 1950–1992. Arthritis Rheum 42:46–50. doi:10.1002/1529-0131(199901)
5. Balluz L, Philen R, Ortega L, Rosales C, Brock J, Barr D et al (2001) Investigation of systemic lupus erythematosus in Nogales, Arizona. Am J Epidemiol 154:1029–1036
6. Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L, Cooper GS (2010) Understanding the epidemiology and progression of systemic lupus erythematosus. Semin Arthritis Rheum 39:257–268. doi:10.1016/j.semarthrit.2008.10.007
7. Arnaud L, Fagot JP, Mathian A, Paita M, Fagot-Campagna A, Amoura Z (2014) Prevalence and incidence of systemic lupus erythematosus in France: a 2010 nation-wide population-based study. Autoimmun Rev 13:1082–1089. doi:10.1016/j.autrev.2014.08.034
8. Chehab G, Fischer-Betz R, Schneider M (2011) Changes in mortality and morbidity in systemic lupus erythematosus. Z Rheumatol 70:480–485. doi:10.1007/s00393-011-0758-x
9. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P et al (2003) Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 82:299–308. doi:10.1097/01.md.0000091181.93122.55
10. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P et al (1999) Morbidity and mortality in systemic lupus erythematosus during a 5-year period. A multicenter prospective study of 1,000 patients. European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 78:167–175
11. Jimenez S, Cervera R, Ingelmo M, Font J (2004) The epidemiology of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Berlin, pp 45–52
12. Gronhagen CM, Fored CM, Granath F, Nyberg F (2011) Cutaneous lupus erythematosus and the association with systemic lupus erythematosus: a population-based cohort of 1088 patients in Sweden. Br J Dermatol 164:1335–1341. doi:10.1111/j.1365-2133.2011.10272.x
13. Lin JH, Dutz JP, Sontheimer RD, Werth VP (2007) Pathophysiology of cutaneous lupus erythematosus. Clin Rev Allergy Immunol 33:85–106. doi:10.1007/s12016-007-0031-x
14. Kuhn A, Wenzel J, Weyd H (2014) Photosensitivity, apoptosis, and cytokines in the pathogenesis of lupus erythematosus: a critical review. Clin Rev Allergy Immunol 47:148–162. doi:10.1007/s12016-013-8403-x
15. Kuhn A, Böhm M, Luger TA (2010) Tissue injury and the skin. In: Lahita R, Buyon J, Koike T (eds) Systemic lupus erythematosus, 5th edn. Elsevier, New York, pp 475–490
16. Mikita N, Ikeda T, Ishiguro M, Furukawa F (2011) Recent advances in cytokines in cutaneous and systemic lupus erythematosus. J Dermatol 38:839–849. doi:10.1111/j.1346-8138.2011.01237.x
17. Ghoreishi M, Dutz JP (2010) Cutaneous lupus erythematosus: recent lessons from animal models. Lupus 19:1029–1035. doi:10.1177/0961203310370045
18. Wenzel J, Zahn S, Tuting T (2010) Pathogenesis of cutaneous lupus erythematosus: common and different features in distinct subsets. Lupus 19:1020–1028. doi:10.1177/0961203310370046
19. Colonna L, Lood C, Elkon KB (2014) Beyond apoptosis in lupus. Curr Opin Rheumatol 26:459–466. doi:10.1097/BOR.0000000000000083
20. Gilliam JN, Sontheimer RD (1981) Distinctive cutaneous subsets in the spectrum of lupus erythematosus. J Am Acad Dermatol 4:471–475
21. Obermoser G, Sontheimer RD, Zelger B (2010) Overview of common, rare and atypical manifestations of cutaneous lupus erythematosus and histopathological correlates. Lupus 19:1050–1070. doi:10.1177/0961203310370048
22. Provost TT (2004) Nonspecific cutaneous manifestations of systemic lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Heidelberg, pp 93–106
23. Kuhn A, Bein D, Bonsmann G (2009) The 100th anniversary of lupus erythematosus tumidus. Autoimmun Rev 8:441–448. doi:10.1016/j.autrev.2008.12.010
24. Kuhn A, Ruzicka T (2004) Classification of cutaneous lupus erythematosus. In: Kuhn A, Lehmann P, Ruzicka T (eds) Cutaneous lupus erythematosus. Springer, Berlin, pp 53–58
25. Wenzel J, Tuting T (2008) An IFN-associated cytotoxic cellular immune response against viral, self-, or tumor antigens is a common pathogenetic feature in “interface dermatitis”. J Investig Dermatol 128:2392–2402. doi:10.1038/jid.2008.96
26. Wenzel J, Worenkamper E, Freutel S, Henze S, Haller O, Bieber T et al (2005) Enhanced type I interferon signalling promotes Th1-biased inflammation in cutaneous lupus erythematosus. J Pathol 205:435–442. doi:10.1002/path.1721
27. Wenzel J, Proelss J, Wiechert A, Zahn S, Bieber T, Tuting T (2007) CXCR3-mediated recruitment of cytotoxic lymphocytes in lupus erythematosus profundus. J Am Acad Dermatol 56:648–650. doi:10.1016/j.jaad.2006.08.014
28. Lipsker D (2006) Classification of specific cutaneous manifestations in patients with lupus erythematosus: a time for change? The concept of dermal lupus erythematosus. Dermatology 212:324–326. doi:10.1159/000092282
29. Gonzalez EG, Selvi E, Lorenzini S, Maggio R, Mannucci S, Galeazzi M et al (2007) Subcutaneous panniculitis-like T-cell lymphoma misdiagnosed as lupus erythematosus panniculitis. Clin Rheumatol 26:244–246. doi:10.1007/s10067-005-0125-x
30. Cardinali C, Caproni M, Fabbri P (1999) The composition of the lupus band test (LBT) on the sun-protected non-lesional (SPNL) skin in patients with cutaneous lupus erythematosus (CLE). Lupus 8:755–760. doi:10.1191/096120399678840945
31. George R, Kurian S, Jacob M, Thomas K (1995) Diagnostic evaluation of the lupus band test in discoid and systemic lupus erythematosus. Int J Dermatol 34:170–173
32. Williams RE, Mackie RM, O’Keefe R, Thomson W (1989) The contribution of direct immunofluorescence to the diagnosis of lupus erythematosus. J Cutan Pathol 16:122–125. doi:10.1111/j.1600-0560.1989.tb00025.x
33. Lazaridou E, Apalla Z, Sotiraki S, Ziakas NG, Fotiadou C, Ioannides D (2010) Clinical and laboratory study of rosacea in northern Greece. J Eur Acad Dermatol Venereol 24:410–414. doi:10.1111/j.1468-3083.2009.03424.x
34. Jablonska S, Chorzelski T, Maciejowska E (1970) The scope and limitations of the immunofluorescence method in the diagnosis of lupus erythematosus. Br J Dermatol 83:242–247. doi:10.1111/j.1365-2133.1970.tb15694.x
35. Costner MI, Sontheimer RD, Provost TT (2003) Lupus erythematosus. In: Sontheimer RD, Provost TT (eds) Cutaneous manifestations of rheumatic diseases. Williams & Wilkins, Philadelphia, pp 15–64
36. Kuhn A, Landmann A (2014) The classification and diagnosis of cutaneous lupus erythematosus. J Autoimmun 48–49:14–19. doi:10.1016/j.jaut.2014.01.021
37. Baltaci M, Fritsch P (2009) Histologic features of cutaneous lupus erythematosus. Autoimmun Rev 8:467–473. doi:10.1016/j.autrev.2008.12.014
38. Sontheimer RD (2005) 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 4:253–263
39. Milde P, Goerz G (1994) Depigmentierung bei Lupus erythematodes (LE) - Klinischer “Clue” zum subakut kutanen Lupus erythematodes (SCLE). Z Hautkr 69:123–126
40. Sontheimer RD, Thomas JR, Gilliam JN (1979) Subacute cutaneous lupus erythematosus: a cutaneous marker for a distinct lupus erythematosus subset. Arch Dermatol 115:1409–1415. doi:10.1001/archderm.1979.04010120007006
41. Chang YH, Wang SH, Chi CC (2006) Discoid lupus erythematosus presenting as acneiform pitting scars. Int J Dermatol 45:944–945. doi:10.1111/j.1365-4632.2006.02899.x
42. Helm TN, Jones CM (2002) Chilblain lupus erythematosus lesions precipitated by the cold. Cutis 69:183–184
43. Aringer M, Lee-Kirsch MA, Kuhn A (2012) Chilblain lupus erythematosus. In: Matucci-Cerinic M, Warren P (eds) Rheumatic diseases and the skin. Elsevier, New York, pp 13–19
44. Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P (2000) Lupus erythematosus tumidus-a neglected subset of cutaneous Lupus erythematosus: report of 40 cases. Arch Dermatol 136:1033–1041. doi:10.1001/archderm.136.8.1033
45. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T et al (2001) Phototesting in lupus erythematosus tumidus-review of 60 patients. Photochem Photobiol 73:532–536. doi:10.1562/0031-8655(2001)
46. Schmitt V, Meuth AM, Amler S, Kuehn E, Haust M, Messer G et al (2010) Lupus erythematosus tumidus is a separate subtype of cutaneous lupus erythematosus. Br J Dermatol 162:64–73. doi:10.1111/j.1365-2133.2009.09401.x
47. Tomasini D, Mentzel T, Hantschke M, Cerri A, Paredes B, Rutten A et al (2010) Plasmacytoid dendritic cells: an overview of their presence and distribution in different inflammatory skin diseases, with special emphasis on Jessner’s lymphocytic infiltrate of the skin and cutaneous lupus erythematosus. J Cutan Pathol 37:1132–1139. doi:10.1111/j.1600-0560.2010.01587.x
48. Rekvig OP, Van der Vlag J (2014) The pathogenesis and diagnosis of systemic lupus erythematosus: still not resolved. Semin Immunopathol 36:301–311. doi:10.1007/s00281-014-0428-6
49. Yu C, Chang C, Zhang J (2013) Immunologic and genetic considerations of cutaneous lupus erythematosus: a comprehensive review. J Autoimmun 41:34–45. doi:10.1016/j.jaut.2013.01.007
50. Kuhn A, Ruland V, Bonsmann G (2010) Photosensitivity, phototesting, and photoprotection in cutaneous lupus erythematosus. Lupus 19:1036–1046. doi:10.1177/0961203310370344
51. Maverakis E, Miyamura Y, Bowen MP, Correa G, Ono Y, Goodarzi H (2010) Light, including ultraviolet. J Autoimmun 34:J247–J257. doi:10.1016/j.jaut.2009.11.011
52. Balogh TS, Velasco MV, Pedriali CA, Kaneko TM, Baby AR (2011) Ultraviolet radiation protection: current available resources in photoprotection. An Bras Dermatol 86:732–742. doi:10.1590/S0365-05962011000400016
53. Furukawa F, Kashihara-Sawami M, Lyons MB, Norris DA (1990) Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus. J Investig Dermatol 94:77–85
54. Golan TD, Elkon KB, Gharavi AE, Krueger JG (1992) Enhanced membrane binding of autoantibodies to cultured keratinocytes of systemic lupus erythematosus patients after ultraviolet B/ultraviolet A irradiation. J Clin Invest 90:1067–1076. doi:10.1172/JCI115922
55. LeFeber WP, Norris DA, Ryan SR, Huff JC, Lee LA, Kubo M et al (1984) Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest 74:1545–1551. doi:10.1172/JCI111569
56. Cazenave P (1851) Lupus erythematoux (erytheme centrifuge). Ann Mal Peau Syph 3:297–299
57. Freund H (1929) Inwiefern ist der Lupus erythematodes von allgemeinen Faktoren abhängig? Dermatol Wochenschr 89:1939–1946
58. Fuhs E (1922) Lupus erythematodes subacutus mit ausgesprochener Überempfindlichkeit gegen Quarzlicht. Z Hautkr 30:308–309
59. Hutchinson J (1888) Harveian lectures on lupus. Lecture III. On the various form of lupus vulgaris and erythematosus. Br Med J 1:113–118
60. Pusey W (1915) Attacks of lupus erythematosus following exposure to sunlight or weather factors. Arch Dermatol Syph 33:388
61. Reed BR, Huff JC, Jones SK, Orton PW, Lee LA, Norris DA (1985) Subacute cutaneous lupus erythematosus associated with hydrochlorothiazide therapy. Ann Intern Med 103:49–51. doi:10.7326/0003-4819-103-1-49
62. Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40:1725. doi:10.1002/art.1780400928
63. Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277. doi:10.1002/art.1780251101
64. Nyberg F, Hasan T, Puska P, Stephansson E, Hakkinen M, Ranki A et al (1997) Occurrence of polymorphous light eruption in lupus erythematosus. Br J Dermatol 136:217–221. doi:10.1111/j.1365-2133.1997.tb14899.x
65. Albrecht J, Berlin JA, Braverman IM, Callen JP, Connolly MK, Costner MI et al (2004) Dermatology position paper on the revision of the 1982 ACR criteria for systemic lupus erythematosus. Lupus 13:839–849. doi:10.1191/0961203304lu2020oa
66. Petri M, Orbai AM, Alarcon GS, Gordon C, Merrill JT, Fortin PR et al (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677–2686. doi:10.1002/art.34473
67. Jong CT, Finlay AY, Pearse AD, Kerr AC, Ferguson J, Benton EC et al (2008) The quality of life of 790 patients with photodermatoses. Br J Dermatol 159:192–197. doi:10.1111/j.1365-2133.2008.08581.x
68. Morison WL (2004) Clinical practice. Photosensitivity. N Engl J Med 350:1111–1117. doi:10.1056/NEJMcp022558
69. Tzaneva S, Volc-Platzer B, Kittler H, Honigsmann H, Tanew A (2008) Antinuclear antibodies in patients with polymorphic light eruption: a long-term follow-up study. Br J Dermatol 158:1050–1054. doi:10.1111/j.1365-2133.2008.08500.x
70. Hasan T, Stephansson E, Ranki A (1999) Distribution of naive and memory T-cells in photoprovoked and spontaneous skin lesions of discoid lupus erythematosus and polymorphous light eruption. Acta Derm Venereol 79:437–442. doi:10.1080/000155599750009861
71. Foering K, Chang AY, Piette EW, Cucchiara A, Okawa J, Werth VP (2013) Characterization of clinical photosensitivity in cutaneous lupus erythematosus. J Am Acad Dermatol 69:205–213. doi:10.1016/j.jaad.2013.03.015
72. Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T et al (2001) Phototesting in lupus erythematosus: a 15-year experience. J Am Acad Dermatol 45:86–95. doi:10.1067/mjd.2001.114589
73. Foering K, Goreshi R, Klein R, Okawa J, Rose M, Cucchiara A et al (2012) Prevalence of self-report photosensitivity in cutaneous lupus erythematosus. J Am Acad Dermatol 66:220–228. doi:10.1016/j.jaad.2010.12.006
74. Schmidt E, Tony HP, Brocker EB, Kneitz C (2007) Sun-induced life-threatening lupus nephritis. Ann N Y Acad Sci 1108:35–40. doi:10.1196/annals.1422.004
75. Klein RS, Sayre RM, Dowdy JC, Werth VP (2009) The risk of ultraviolet radiation exposure from indoor lamps in lupus erythematosus. Autoimmun Rev 8:320–324. doi:10.1016/j.autrev.2008.10.003
76. Klein RS, Werth VP, Dowdy JC, Sayre RM (2009) Analysis of compact fluorescent lights for use by patients with photosensitive conditions. Photochem Photobiol 85:1004–1010. doi:10.1111/j.1751-1097.2009.00540.x
77. Kuhn A, Beissert S (2005) Photosensitivity in lupus erythematosus. Autoimmunity 38:519–529
78. Epstein JH, Tuffanelli D, Dubois EL (1965) Light sensitivity and lupus erythematosus. Arch Dermatol 91:483–485
79. Lehmann P, Hölzle E, von Kries R, Plewig G (1986) Lichtdiagnostische Verfahren bei Patienten mit Verdacht auf Photodermatosen. Zentrbl Hug 152:667–682. doi:10.1007/978-3-642-72828-0_8
80. Lehmann P, Hölzle E, Kind P, Goerz G, Plewig G (1990) Experimental reproduction of skin lesions in lupus erythematosus by UVA and UVB radiation. J Am Acad Dermatol 22:181–187
81. Ruland V, Haust M, Stilling RM, Amler S, Ruzicka T, Kuhn A (2013) Updated analysis of standardised photoprovocation in patients with cutaneous lupus erythematosus. Arthritis Care Res 65:767–776. doi:10.1002/acr.21867
82. Kuhn A, Wozniacka A, Szepietowski JC, Glaser R, Lehmann P, Haust M et al (2011) Photoprovocation in cutaneous lupus erythematosus: a multicenter study evaluating a standardized protocol. J Investig Dermatol 131:1622–1630. doi:10.1038/jid.2011.101
83. Zahn S, Graef M, Patsinakidis N, Landmann A, Surber C, Wenzel J et al (2014) Ultraviolet light protection by a sunscreen prevents interferon-driven skin inflammation in cutaneous lupus erythematosus. Exp Dermatol 23:516–518. doi:10.1111/exd.12428
84. Patsinakidis N, Wenzel J, Landmann A, Koch R, Gerss J, Luger TA et al (2012) Suppression of UV-induced damage by a liposomal sunscreen: a prospective, open-label study in patients with cutaneous lupus erythematosus and healthy controls. Exp Dermatol 21:958–961. doi:10.1111/exd.12035
85. Golstein P, Kroemer G (2007) Cell death by necrosis: towards a molecular definition. Trends Biochem Sci 32:37–43. doi:10.1016/j.tibs.2006.11.001
86. Courtney PA, Crockard AD, Williamson K, Irvine AE, Kennedy RJ, Bell AL (1999) Increased apoptotic peripheral blood neutrophils in systemic lupus erythematosus: relations with disease activity, antibodies to double stranded DNA, and neutropenia. Ann Rheum Dis 58:309–314
87. Kuhn A, Herrmann M, Kleber S, Beckmann-Welle M, Fehsel K, Martin-Villalba A et al (2006) Accumulation of apoptotic cells in the epidermis of patients with cutaneous lupus erythematosus after ultraviolet irradiation. Arthritis Rheum 54:939–950. doi:10.1002/art.21658
88. Baumann I, Kolowos W, Voll RE, Manger B, Gaipl U, Neuhuber WL et al (2002) Impaired uptake of apoptotic cells into tangible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 46:191–201. doi:10.1002/1529-0131(200201)46:1<191::AID-ART10027>3.0.CO;2-K
89. Reefman E, de Jong MC, Kuiper H, Jonkman MF, Limburg PC, Kallenberg CG et al (2006) Is disturbed clearance of apoptotic keratinocytes responsible for UVB-induced inflammatory skin lesions in systemic lupus erythematosus? Arthritis Res Ther 8:R156. doi:10.1186/ar2051
90. Biermann MH, Veissi S, Maueroder C, Chaurio R, Berens C, Herrmann M et al (2014) The role of dead cell clearance in the etiology and pathogenesis of systemic lupus erythematosus: dendritic cells as potential targets. Expert Rev Clin Immunol 10:1151–1164. doi:10.1586/1744666X.2014.944162
91. Khan TN, Wong EB, Soni C, Rahman ZS (2013) Prolonged apoptotic cell accumulation in germinal centers of Mer-deficient mice causes elevated B cell and CD4+ Th cell responses leading to autoantibody production. J Immunol 190:1433–1446. doi:10.4049/jimmunol.1200824
92. Botto M, Dell’Agnola C, Bygrave AE, Thompson EM, Cook HT, Petry F et al (1998) Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies. Nat Genet 19:56–59. doi:10.1038/ng0598-56
93. Botto M, Walport MJ (2002) C1q, autoimmunity and apoptosis. Immunobiology 205:395–406. doi:10.1078/0171-2985-00141
94. Pieterse E, van der Vlag J (2014) Breaking immunological tolerance in systemic lupus erythematosus. Front Immunol 5:164. doi:10.3389/fimmu.2014.00164
95. Yu Y, Su K (2013) Neutrophil extracellular traps and systemic lupus erythematosus. J Clin Cell Immunol 4. doi:10.4172/2155-9899.1000139
96. Douda DN, Yip L, Khan MA, Grasemann H, Palaniyar N (2014) Akt is essential to induce NADPH-dependent NETosis and to switch the neutrophil death to apoptosis. Blood 123:597–600. doi:10.1182/blood-2013-09-526707
97. Hakkim A, Furnrohr BG, Amann K, Laube B, Abed UA, Brinkmann V et al (2010) Impairment of neutrophil extracellular trap degradation is associated with lupus nephritis. Proc Natl Acad Sci U S A 107:9813–9818. doi:10.1073/pnas.0909927107
98. Schorn C, Janko C, Latzko M, Chaurio R, Schett G, Herrmann M (2012) Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells. Front Immunol 3:277. doi:10.3389/fimmu.2012.00277
99. Knight JS, Carmona-Rivera C, Kaplan MJ (2012) Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases. Front Immunol 3:380. doi:10.3389/fimmu.2012.00380
100. Obermoser G, Pascual V (2010) The interferon-alpha signature of systemic lupus erythematosus. Lupus 19:1012–1019. doi:10.1177/0961203310371161
101. Warde N (2011) Autoimmunity: the role of neutrophils in SLE: untangling the NET. Nat Rev Rheumatol 7:252. doi:10.1038/nrrheum.2011.41
102. Clarke AJ, Ellinghaus U, Cortini A, Stranks A, Simon AK, Botto M et al (2015) Autophagy is activated in systemic lupus erythematosus and required for plasmablast development. Ann Rheum Dis 74:912–920. doi:10.1136/annrheumdis-2013-204343
103. Li B, Yue Y, Dong C, Shi Y, Xiong S (2014) Blockade of macrophage autophagy ameliorates activated lymphocytes-derived DNA induced murine lupus possibly via inhibition of proinflammatory cytokine production. Clin Exp Rheumatol 32:705–714
104. Cook KL, Warri A, Soto-Pantoja DR, Clarke PA, Cruz MI, Zwart A et al (2014) Hydroxychloroquine inhibits autophagy to potentiate antiestrogen responsiveness in ER+ breast cancer. Clin Cancer Res 20:3222–3232. doi:10.1158/1078-0432.CCR-13-3227
105. Monneaux F, Hoebeke J, Sordet C, Nonn C, Briand JP, Maillere B et al (2005) Selective modulation of CD4+ T cells from lupus patients by a promiscuous, protective peptide analog. J Immunol 175:5839–5847
106. Alessandri C, Barbati C, Vacirca D, Piscopo P, Confaloni A, Sanchez M et al (2012) T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy. FASEB J 26:4722–4732. doi:10.1096/fj.12-206060
107. Linkermann A, Green DR (2014) Necroptosis. N Engl J Med 370:455–465. doi:10.1056/NEJMra1310050
108. Ch’en IL, Tsau JS, Molkentin JD, Komatsu M, Hedrick SM (2011) Mechanisms of necroptosis in T cells. J Exp Med 208:633–641. doi:10.1084/jem.20110251
109. Fan H, Liu F, Dong G, Ren D, Xu Y, Dou J et al (2014) Activation-induced necroptosis contributes to B-cell lymphopenia in active systemic lupus erythematosus. Cell Death Dis 5, e1416. doi:10.1038/cddis.2014.375
110. Mohan C, Putterman C (2015) Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis. Nat Rev Nephrol 11:329–341. doi:10.1038/nrneph.2015.33
111. Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Moroy T (2000) Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet 25:177–181
112. Andersson U, Rauvala H (2011) Introduction: HMGB1 in inflammation and innate immunity. J Intern Med 270:296–300. doi:10.1111/j.1365-2796.2011.02430.x
113. Chen GY, Tang J, Zheng P, Liu Y (2009) CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science 323:1722–1725. doi:10.1126/science.1168988
114. van Zoelen MA, Yang H, Florquin S, Meijers JC, Akira S, Arnold B et al (2009) Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo. Shock 31:280–284. doi:10.1097/SHK.0b013e318186262d
115. Schiraldi M, Raucci A, Munoz LM, Livoti E, Celona B, Venereau E et al (2012) HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209:551–563. doi:10.1084/jem.20111739
116. Tadie JM, Bae HB, Jiang S, Park DW, Bell CP, Yang H et al (2013) HMGB1 promotes neutrophil extracellular trap formation through interactions with Toll-like receptor 4. Am J Physiol Lung Cell Mol Physiol 304:L342–L349. doi:10.1152/ajplung.00151.2012
117. Venereau E, Casalgrandi M, Schiraldi M, Antoine DJ, Cattaneo A, De Marchis F et al (2012) Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med 209:1519–1528. doi:10.1084/jem.20120189
118. Yang H, Wang H, Ju Z, Ragab AA, Lundback P, Long W et al (2015) MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J Exp Med 212:5–14. doi:10.1084/jem.20141318
119. Tian J, Avalos AM, Mao SY, Chen B, Senthil K, Wu H et al (2007) Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496. doi:10.1038/ni1457
120. Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M et al (2003) High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 48:971–981. doi:10.1002/art.10859
121. Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J et al (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251
122. Johnson KE, Wulff BC, Oberyszyn TM, Wilgus TA (2013) Ultraviolet light exposure stimulates HMGB1 release by keratinocytes. Arch Dermatol Res 305:805–815. doi:10.1007/s00403-013-1401-2
123. Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Lopez-Ramos D et al (2014) Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507:109–113. doi:10.1038/nature13111
124. Schierbeck H, Lundback P, Palmblad K, Klevenvall L, Erlandsson-Harris H, Andersson U et al (2011) Monoclonal anti-HMGB1 (high mobility group box chromosomal protein 1) antibody protection in two experimental arthritis models. Mol Med 17:1039–1044. doi:10.2119/molmed.2010.00264
125. Shimazaki J, Matsumoto N, Ogura H, Muroya T, Kuwagata Y, Nakagawa J et al (2012) Systemic involvement of high-mobility group box 1 protein and therapeutic effect of anti-high-mobility group box 1 protein antibody in a rat model of crush injury. Shock 37:634–638. doi:10.1097/SHK.0b013e31824ed6b7
126. Yang H, Hreggvidsdottir HS, Palmblad K, Wang H, Ochani M, Li J et al (2010) A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci U S A 107:11942–11947. doi:10.1073/pnas.1003893107
127. Wen Z, Xu L, Chen X, Xu W, Yin Z, Gao X et al (2013) Autoantibody induction by DNA-containing immune complexes requires HMGB1 with the TLR2/microRNA-155 pathway. J Immunol 190:5411–5422. doi:10.4049/jimmunol.1203301
128. Abdulahad DA, Westra J, Horst G (2011) HMGB1 is an important mediator in cutaneous inflammation in systemic lupus erythematosus (SLE). Arthritis Rheum 63:S649
129. Abdulahad DA, Westra J, Bijzet J, Dolff S, van Dijk MC, Limburg PC et al (2012) Urine levels of HMGB1 in systemic lupus erythematosus patients with and without renal manifestations. Arthritis Res Ther 14:R184. doi:10.1186/ar4015
130. Li J, Xie H, Wen T, Liu H, Zhu W, Chen X (2010) Expression of high mobility group box chromosomal protein 1 and its modulating effects on downstream cytokines in systemic lupus erythematosus. J Rheumatol 37:766–775. doi:10.3899/jrheum.090663
131. Ma CY, Jiao YL, Zhang J, Yang QR, Zhang ZF, Shen YJ et al (2012) Elevated plasma level of HMGB1 is associated with disease activity and combined alterations with IFN-alpha and TNF-alpha in systemic lupus erythematosus. Rheumatol Int 32:395–402. doi:10.1007/s00296-010-1636-6
132. Zickert A, Palmblad K, Sundelin B, Chavan S, Tracey KJ, Bruchfeld A et al (2012) Renal expression and serum levels of high mobility group box 1 protein in lupus nephritis. Arthritis Res Ther 14:R36. doi:10.1186/ar3747
133. Urbonaviciute V, Meister S, Furnrohr BG, Frey B, Guckel E, Schett G et al (2009) Oxidation of the alarmin high-mobility group box 1 protein (HMGB1) during apoptosis. Autoimmunity 42:305–307. doi:10.1080/08916930902831803
134. Popovic K, Ek M, Espinosa A, Padyukov L, Harris HE, Wahren-Herlenius M et al (2005) Increased expression of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in skin lesions of patients with lupus erythematosus. Arthritis Rheum 52:3639–3645. doi:10.1002/art.21398
135. Barkauskaite V, Ek M, Popovic K, Harris HE, Wahren-Herlenius M, Nyberg F (2007) 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 16:794–802. doi:10.1177/0961203307081895
136. de Souza AW, van der Geest KS, Brouwer E, Pinheiro FA, Oliveira AC, Sato EI et al (2015) High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins. Arthritis Res Ther 17:158. doi:10.1186/s13075-015-0672-8
137. Ronnblom L, Eloranta ML, Alm GV (2006) The type I interferon system in systemic lupus erythematosus. Arthritis Rheum 54:408–420. doi:10.1002/art.21571
138. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ et al (2003) Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100:2610–2615. doi:10.1073/pnas.0337679100
139. Bennett L, Palucka AK, Arce E, Cantrell V, Borvak J, Banchereau J et al (2003) Interferon and granulopoiesis signatures in systemic lupus erythematosus blood. J Exp Med 197:711–723. doi:10.1084/jem.20021553
140. Dall’era MC, Cardarelli PM, Preston BT, Witte A, Davis JC Jr (2005) Type I interferon correlates with serological and clinical manifestations of SLE. Ann Rheum Dis 64:1692–1697. doi:10.1136/ard.2004.033753
141. Kalunian KC, Merrill JT, Maciuca R, McBride JM, Townsend MJ, Wei X et al (2015) A phase II study of the efficacy and safety of rontalizumab (rhuMAb interferon-alpha) in patients with systemic lupus erythematosus (ROSE). Ann Rheum Dis. doi:10.1136/annrheumdis-2014-206090
142. Petri M, Wallace DJ, Spindler A, Chindalore V, Kalunian K, Mysler E et al (2013) Sifalimumab, a human anti-interferon-alpha monoclonal antibody, in systemic lupus erythematosus: a phase I randomized, controlled, dose-escalation study. Arthritis Rheum 65:1011–1021. doi:10.1002/art.37824
143. Wenzel J, Tuting T (2007) Identification of type I interferon-associated inflammation in the pathogenesis of cutaneous lupus erythematosus opens up options for novel therapeutic approaches. Exp Dermatol 16:454–463. doi:10.1111/j.1600-0625.2007.00556.x
144. Arrue I, Saiz A, Ortiz-Romero PL, Rodriguez-Peralto JL (2007) Lupus-like reaction to interferon at the injection site: report of five cases. J Cutan Pathol 34(Suppl 1):18–21. doi:10.1111/j.1600-0560.2007.00715.x
145. Conroy M, Sewell L, Miller OF, Ferringer T (2008) Interferon-beta injection site reaction: review of the histology and report of a lupus-like pattern. J Am Acad Dermatol 59:S48–S49
146. Braunstein I, Klein R, Okawa J, Werth VP (2012) The interferon-regulated gene signature is elevated in subacute cutaneous lupus erythematosus and discoid lupus erythematosus and correlates with the cutaneous lupus area and severity index score. Br J Dermatol 166:971–975. doi:10.1111/j.1365-2133.2012.10825.x
147. Zahn S, Rehkamper C, Ferring-Schmitt S, Bieber T, Tuting T, Wenzel J (2011) Interferon-alpha stimulates TRAIL expression in human keratinocytes and peripheral blood mononuclear cells: implications for the pathogenesis of cutaneous lupus erythematosus. Br J Dermatol 165:1118–1123. doi:10.1111/j.1365-2133.2011.10479.x
148. Wenzel J, Zahn S, Mikus S, Wiechert A, Bieber T, Tuting T (2007) 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 157:752–757. doi:10.1111/j.1365-2133.2007.08137.x
149. Vallin H, Perers A, Alm GV, Ronnblom L (1999) Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-alpha inducer in systemic lupus erythematosus. J Immunol 163:6306–6313
150. Means TK, Latz E, Hayashi F, Murali MR, Golenbock DT, Luster AD (2005) Human lupus autoantibody-DNA complexes activate DCs through cooperation of CD32 and TLR9. J Clin Invest 115:407–417. doi:10.1172/JCI200523025
151. Lovgren T, Eloranta ML, Bave U, Alm GV, Ronnblom L (2004) Induction of interferon-alpha production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG. Arthritis Rheum 50:1861–1872. doi:10.1002/art.20254
152. Barrat FJ, Meeker T, Gregorio J, Chan JH, Uematsu S, Akira S et al (2005) Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202:1131–1139. doi:10.1084/jem.20050914
153. Gaipl US, Voll RE, Sheriff A, Franz S, Kalden JR, Herrmann M (2005) Impaired clearance of dying cells in systemic lupus erythematosus. Autoimmun Rev 4:189–194. doi:10.1016/j.autrev.2004.10.007
154. Herrmann M, Winkler T, Gaipl U, Lorenz H, Geiler T, Kalden JR (2000) Etiopathogenesis of systemic lupus erythematosus. Int Arch Allergy Immunol 123:28–35. doi:10.1159/000024421
155. Gunther C, Meurer M, Stein A, Viehweg A, Lee-Kirsch MA (2009) Familial chilblain lupus-a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1. Dermatology 219:162–166. doi:10.1159/000222430
156. Ablasser A, Hemmerling I, Schmid-Burgk JL, Behrendt R, Roers A, Hornung V (2014) TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. J Immunol 192:5993–5997. doi:10.4049/jimmunol.1400737
157. Gehrke N, Mertens C, Zillinger T, Wenzel J, Bald T, Zahn S et al (2013) Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity 39:482–495. doi:10.1016/j.immuni.2013.08.004
158. Wenzel J, Bauer R, Bieber T, Boehm I (2000) Presence of antinuclear antibodies in patients with lupus erythematosus is correlated with diminished T-helper cells. Br J Dermatol 143:1100–1101. doi:10.1046/j.1365-2133.2000.03861.x
159. Casciola-Rosen LA, Anhalt G, Rosen A (1994) Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med 179:1317–1330
160. Toberer F, Sykora J, Gottel D, Hartschuh W, Werchau S, Enk A et al (2013) Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus: analysis using tissue microarray. Exp Dermatol 22:656–659. doi:10.1111/exd.12216
161. Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P et al (2009) Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum 60:1785–1796. doi:10.1002/art.24557
162. Lauwerys BR, Ducreux J, Houssiau FA (2014) Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatology (Oxford) 53:1369–1376. doi:10.1093/rheumatology/ket403
163. Chan ES, Herlitz LC, Jabbari A (2015) Ruxolitinib attenuates cutaneous lupus development in a mouse lupus model. J Investig Dermatol 135:1912–1915. doi:10.1038/jid.2015.107
164. Hornung T, Janzen V, Heidgen FJ, Wolf D, Bieber T, Wenzel J (2014) Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 371:2537–2538. doi:10.1056/NEJMc1412997
165. Hornung T, Wolf D, Wenzel J (2015) More on remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 372:1274. doi:10.1056/NEJMc1500688
166. Zaba LC, Fiorentino DF (2012) Skin disease in dermatomyositis. Curr Opin Rheumatol 24:597–601. doi:10.1097/BOR.0b013e3283585748
167. Ching KH, Burbelo PD, Tipton C, Wei C, Petri M, Sanz I et al (2012) Two major autoantibody clusters in systemic lupus erythematosus. PLoS One 7, e32001. doi:10.1371/journal.pone.0032001
168. Liu Z, Davidson A (2012) Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med 18:871–882. doi:10.1038/nm.2752