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Erschienen in: Clinical Rheumatology 4/2017

26.01.2017 | Original Article

Human cytomegalovirus (HCMV) UL44 and UL57 specific antibody responses in anti-HCMV-positive patients with systemic sclerosis

verfasst von: Emmanouela Marou, Christos Liaskos, Theodora Simopoulou, Georgios Efthymiou, Efthymios Dardiotis, Christina Katsiari, Thomas Scheper, Wolfgang Meyer, Georgios Hadjigeorgiou, Dimitrios P. Bogdanos, Lazaros I. Sakkas

Erschienen in: Clinical Rheumatology | Ausgabe 4/2017

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Abstract

The role of human cytomegalovirus (HCMV) has been postulated as a trigger of systemic sclerosis (SSc). The aim of the study was to assess the prevalence of antibodies against HCMV UL44 and UL57 antigens not tested in the past. Sixty SSc patients, 40 multiple sclerosis and 17 normal controls (NCs), all anti-HCMV positive, were tested by immunoblotting. Reactivity to HCMV antigens, expressed as arbitrary units (AUs), was assessed for correlation with clinical and immunological parameters, including types of SSc-related autoantibodies. Anti-UL44 and anti-UL57 HCMV antibodies were present in 3/60 (5%) and 58/60 (96.7%) SSc patients, respectively (p < 0.001). Anti-UL57 antibodies were present in 35/40 (87.5%) MS patients and 16/17 (94.1%) NCs (SSc vs MS, MS vs NC, p = ns). Strong (50-75 AU) and very strong (75–100 AU) anti-UL57 immunoreactivity was found in 24 (41.4%) and 22 (37.9%) SSc patients, respectively (p = ns). Dilution experiments showed anti-UL57 antibody persistence in up to 1/5000. Overall, there was no difference in the frequency or the magnitude of anti-UL57 immunoreactivity between diffuse cutaneous systemic sclerosis and limited cutaneous systemic sclerosis patients (96.67 vs 96.67%; 65.45 ± 20.19 vs 64.31 ± 21.11 AU, p > 0.05) but strong anti-UL57 reactivity were more frequent in SSc compared to NCs (p = 0.007). Anti-UL57 reactivity was not inhibited by SSc-specific autoantigens. Anti-UL57 seropositivity did not correlate with demographic, clinical or immunological features of SSc. Anti-HCMV UL57 antibodies are universally present in anti-HCMV-positive patients with SSc, while those against UL44 are rarely seen. Because anti-UL57 lack disease specificity and are not involved in cross-reactive responses, their immunopathogenetic potential is to be questioned.
Literatur
1.
Zurück zum Zitat Sakkas LI, Chikanza IC, Platsoucas CD (2012) Systemic sclerosis: from pathogenesis towards targeted immunotherapies. Curr Rheumatol Rev 8:45–55CrossRef Sakkas LI, Chikanza IC, Platsoucas CD (2012) Systemic sclerosis: from pathogenesis towards targeted immunotherapies. Curr Rheumatol Rev 8:45–55CrossRef
2.
Zurück zum Zitat Chora I, Guiducci S, Manetti M, Romano E, Mazzotta C, Bellando-Randone S, Ibba-Manneschi L, Matucci-Cerinic M, Soares R (2015) Vascular biomarkers and correlation with peripheral vasculopathy in systemic sclerosis. Autoimmun Rev 14(4):314–322. doi:10.1016/j.autrev.2014.12.001 CrossRefPubMed Chora I, Guiducci S, Manetti M, Romano E, Mazzotta C, Bellando-Randone S, Ibba-Manneschi L, Matucci-Cerinic M, Soares R (2015) Vascular biomarkers and correlation with peripheral vasculopathy in systemic sclerosis. Autoimmun Rev 14(4):314–322. doi:10.​1016/​j.​autrev.​2014.​12.​001 CrossRefPubMed
4.
9.
Zurück zum Zitat Riccieri V, Parisi G, Spadaro A, Scrivo R, Barone F, Moretti T, Bernardini G, Strom R, Taccari E, Valesini G (2005) Reduced circulating natural killer T cells and gamma/delta T cells in patients with systemic sclerosis. J Rheumatol 32(2):283–286PubMed Riccieri V, Parisi G, Spadaro A, Scrivo R, Barone F, Moretti T, Bernardini G, Strom R, Taccari E, Valesini G (2005) Reduced circulating natural killer T cells and gamma/delta T cells in patients with systemic sclerosis. J Rheumatol 32(2):283–286PubMed
14.
Zurück zum Zitat Bogdanos DP, Smyk DS, Invernizzi P, Rigopoulou EI, Blank M, Sakkas L, Pouria S, Shoenfeld Y (2013) Tracing environmental markers of autoimmunity: introducing the infectome. Immunol Res 56(2–3):220–240. doi:10.1007/s12026-013-8399-6 CrossRefPubMed Bogdanos DP, Smyk DS, Invernizzi P, Rigopoulou EI, Blank M, Sakkas L, Pouria S, Shoenfeld Y (2013) Tracing environmental markers of autoimmunity: introducing the infectome. Immunol Res 56(2–3):220–240. doi:10.​1007/​s12026-013-8399-6 CrossRefPubMed
15.
Zurück zum Zitat Elisa T, Antonio P, Giuseppe P, Alessandro B, Giuseppe A, Federico C, Marzia D, Ruggero B, Giacomo M, Andrea O, Daniela R, Mariaelisa R, Claudio L (2015) Endothelin receptors expressed by immune cells are involved in modulation of inflammation and in fibrosis: relevance to the pathogenesis of systemic sclerosis. J Immunol Res 2015:147616. doi:10.1155/2015/147616 CrossRefPubMedPubMedCentral Elisa T, Antonio P, Giuseppe P, Alessandro B, Giuseppe A, Federico C, Marzia D, Ruggero B, Giacomo M, Andrea O, Daniela R, Mariaelisa R, Claudio L (2015) Endothelin receptors expressed by immune cells are involved in modulation of inflammation and in fibrosis: relevance to the pathogenesis of systemic sclerosis. J Immunol Res 2015:147616. doi:10.​1155/​2015/​147616 CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Pandey JP (2004) Immunoglobulin GM genes and IgG antibodies to cytomegalovirus in patients with systemic sclerosis. Clin Exp Rheumatol 22(3 Suppl 33):S35–S37PubMed Pandey JP (2004) Immunoglobulin GM genes and IgG antibodies to cytomegalovirus in patients with systemic sclerosis. Clin Exp Rheumatol 22(3 Suppl 33):S35–S37PubMed
19.
Zurück zum Zitat Moinzadeh P, Khan K, Ong VH, Denton CP (2012) Sustained improvement of diffuse systemic sclerosis following human cytomegalovirus infection offers insight into pathogenesis and therapy. Rheumatology (Oxford) 51(12):2296–2298. doi:10.1093/rheumatology/kes137 CrossRef Moinzadeh P, Khan K, Ong VH, Denton CP (2012) Sustained improvement of diffuse systemic sclerosis following human cytomegalovirus infection offers insight into pathogenesis and therapy. Rheumatology (Oxford) 51(12):2296–2298. doi:10.​1093/​rheumatology/​kes137 CrossRef
20.
Zurück zum Zitat Vaughan JH, Shaw PX, Nguyen MD, Medsger TA Jr, Wright TM, Metcalf JS, Leroy EC (2000) Evidence of activation of 2 herpesviruses, Epstein-Barr virus and cytomegalovirus, in systemic sclerosis and normal skins. J Rheumatol 27(3):821–823PubMed Vaughan JH, Shaw PX, Nguyen MD, Medsger TA Jr, Wright TM, Metcalf JS, Leroy EC (2000) Evidence of activation of 2 herpesviruses, Epstein-Barr virus and cytomegalovirus, in systemic sclerosis and normal skins. J Rheumatol 27(3):821–823PubMed
21.
Zurück zum Zitat Dolcino M, Puccetti A, Barbieri A, Bason C, Tinazzi E, Ottria A, Patuzzo G, Martinelli N, Lunardi C (2015) Infections and autoimmunity: role of human cytomegalovirus in autoimmune endothelial cell damage. Lupus 24(4–5):419–432. doi:10.1177/0961203314558677 CrossRefPubMed Dolcino M, Puccetti A, Barbieri A, Bason C, Tinazzi E, Ottria A, Patuzzo G, Martinelli N, Lunardi C (2015) Infections and autoimmunity: role of human cytomegalovirus in autoimmune endothelial cell damage. Lupus 24(4–5):419–432. doi:10.​1177/​0961203314558677​ CrossRefPubMed
22.
Zurück zum Zitat Muryoi T, Kasturi KN, Kafina MJ, Cram DS, Harrison LC, Sasaki T, Bona CA (1992) Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes. J Exp Med 175(4):1103–1109CrossRefPubMed Muryoi T, Kasturi KN, Kafina MJ, Cram DS, Harrison LC, Sasaki T, Bona CA (1992) Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes. J Exp Med 175(4):1103–1109CrossRefPubMed
23.
24.
Zurück zum Zitat Pastano R, Dell’Agnola C, Bason C, Gigli F, Rabascio C, Puccetti A, Tinazzi E, Cetto G, Peccatori F, Martinelli G, Lunardi C (2012) Antibodies against human cytomegalovirus late protein UL94 in the pathogenesis of scleroderma-like skin lesions in chronic graft-versus-host disease. Int Immunol 24(9):583–591. doi:10.1093/intimm/dxs061 CrossRefPubMed Pastano R, Dell’Agnola C, Bason C, Gigli F, Rabascio C, Puccetti A, Tinazzi E, Cetto G, Peccatori F, Martinelli G, Lunardi C (2012) Antibodies against human cytomegalovirus late protein UL94 in the pathogenesis of scleroderma-like skin lesions in chronic graft-versus-host disease. Int Immunol 24(9):583–591. doi:10.​1093/​intimm/​dxs061 CrossRefPubMed
25.
Zurück zum Zitat Namboodiri AM, Rocca KM, Pandey JP (2004) IgG antibodies to human cytomegalovirus late protein UL94 in patients with systemic sclerosis. Autoimmunity 37(3):241–244CrossRefPubMed Namboodiri AM, Rocca KM, Pandey JP (2004) IgG antibodies to human cytomegalovirus late protein UL94 in patients with systemic sclerosis. Autoimmunity 37(3):241–244CrossRefPubMed
26.
Zurück zum Zitat Lunardi C, Bason C, Navone R, Millo E, Damonte G, Corrocher R, Puccetti A (2000) Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells. Nat Med 6(10):1183–1186. doi:10.1038/80533 CrossRefPubMed Lunardi C, Bason C, Navone R, Millo E, Damonte G, Corrocher R, Puccetti A (2000) Systemic sclerosis immunoglobulin G autoantibodies bind the human cytomegalovirus late protein UL94 and induce apoptosis in human endothelial cells. Nat Med 6(10):1183–1186. doi:10.​1038/​80533 CrossRefPubMed
27.
Zurück zum Zitat Lunardi C, Dolcino M, Peterlana D, Bason C, Navone R, Tamassia N, Beri R, Corrocher R, Puccetti A (2006) Antibodies against human cytomegalovirus in the pathogenesis of systemic sclerosis: a gene array approach. PLoS Med 3(1):e2. doi:10.1371/journal.pmed.0030002 CrossRefPubMed Lunardi C, Dolcino M, Peterlana D, Bason C, Navone R, Tamassia N, Beri R, Corrocher R, Puccetti A (2006) Antibodies against human cytomegalovirus in the pathogenesis of systemic sclerosis: a gene array approach. PLoS Med 3(1):e2. doi:10.​1371/​journal.​pmed.​0030002 CrossRefPubMed
28.
Zurück zum Zitat Lunardi C, Dolcino M, Peterlana D, Bason C, Navone R, Tamassia N, Tinazzi E, Beri R, Corrocher R, Puccetti A (2007) Endothelial cells’ activation and apoptosis induced by a subset of antibodies against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis. PLoS One 2(5):e473. doi:10.1371/journal.pone.0000473 CrossRefPubMedPubMedCentral Lunardi C, Dolcino M, Peterlana D, Bason C, Navone R, Tamassia N, Tinazzi E, Beri R, Corrocher R, Puccetti A (2007) Endothelial cells’ activation and apoptosis induced by a subset of antibodies against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis. PLoS One 2(5):e473. doi:10.​1371/​journal.​pone.​0000473 CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT (2002) IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome. Vivo 16(3):153–159 Lerner AM, Beqaj SH, Deeter RG, Fitzgerald JT (2002) IgM serum antibodies to human cytomegalovirus nonstructural gene products p52 and CM2(UL44 and UL57) are uniquely present in a subset of patients with chronic fatigue syndrome. Vivo 16(3):153–159
30.
Zurück zum Zitat Efthymiou G, Dardiotis E, Liaskos C, Marou E, Tsimourtou V, Hadjigeorgiou GM, Scheper T, Meyer W, Daponte A, Sakkas LI, Bogdanos DP (2016) Anti-hsp60 antibody responses based on Helicobacter pylori in patients with multiple sclerosis: (ir)relevance to disease pathogenesis. J Neuroimmunol 298:19–23CrossRefPubMed Efthymiou G, Dardiotis E, Liaskos C, Marou E, Tsimourtou V, Hadjigeorgiou GM, Scheper T, Meyer W, Daponte A, Sakkas LI, Bogdanos DP (2016) Anti-hsp60 antibody responses based on Helicobacter pylori in patients with multiple sclerosis: (ir)relevance to disease pathogenesis. J Neuroimmunol 298:19–23CrossRefPubMed
31.
Zurück zum Zitat Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504. doi:10.1002/art.39437 CrossRefPubMed Mavropoulos A, Simopoulou T, Varna A, Liaskos C, Katsiari CG, Bogdanos DP, Sakkas LI (2016) Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis Rheumatol 68(2):494–504. doi:10.​1002/​art.​39437 CrossRefPubMed
33.
Zurück zum Zitat Barzilai O, Sherer Y, Ram M, Izhaky D, Anaya JM, Shoenfeld Y (2007) Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report. Ann N Y Acad Sci 1108:567–577CrossRefPubMed Barzilai O, Sherer Y, Ram M, Izhaky D, Anaya JM, Shoenfeld Y (2007) Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? A preliminary report. Ann N Y Acad Sci 1108:567–577CrossRefPubMed
35.
Zurück zum Zitat Riccieri V, Alessandri C, Germano V, Guiducci S, Rogai V, Colasanti T, Delunardo F, Margutti P, Ortona E, Cerinic MM, Valesini G (2010) Nedd5, a novel autoantigen in systemic sclerosis: is it a marker of more severe disease? Ann Rheum Dis 69(1):314–315. doi:10.1136/ard.2009.111302 CrossRefPubMed Riccieri V, Alessandri C, Germano V, Guiducci S, Rogai V, Colasanti T, Delunardo F, Margutti P, Ortona E, Cerinic MM, Valesini G (2010) Nedd5, a novel autoantigen in systemic sclerosis: is it a marker of more severe disease? Ann Rheum Dis 69(1):314–315. doi:10.​1136/​ard.​2009.​111302 CrossRefPubMed
36.
Zurück zum Zitat Margutti P, Sorice M, Conti F, Delunardo F, Racaniello M, Alessandri C, Siracusano A, Rigano R, Profumo E, Valesini G, Ortona E (2005) Screening of an endothelial cDNA library identifies the C-terminal region of Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric manifestations. Arthritis Res Ther 7(4):R896–R903. doi:10.1186/ar1759 CrossRefPubMedPubMedCentral Margutti P, Sorice M, Conti F, Delunardo F, Racaniello M, Alessandri C, Siracusano A, Rigano R, Profumo E, Valesini G, Ortona E (2005) Screening of an endothelial cDNA library identifies the C-terminal region of Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric manifestations. Arthritis Res Ther 7(4):R896–R903. doi:10.​1186/​ar1759 CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Riemekasten G, Cabral-Marques O (2016) Antibodies against angiotensin II type 1 receptor (AT1R) and endothelin receptor type A (ETAR) in systemic sclerosis (SSc)-response. Autoimmun Rev. doi:10.1016/j.autrev.2016.04.004 Riemekasten G, Cabral-Marques O (2016) Antibodies against angiotensin II type 1 receptor (AT1R) and endothelin receptor type A (ETAR) in systemic sclerosis (SSc)-response. Autoimmun Rev. doi:10.​1016/​j.​autrev.​2016.​04.​004
Metadaten
Titel
Human cytomegalovirus (HCMV) UL44 and UL57 specific antibody responses in anti-HCMV-positive patients with systemic sclerosis
verfasst von
Emmanouela Marou
Christos Liaskos
Theodora Simopoulou
Georgios Efthymiou
Efthymios Dardiotis
Christina Katsiari
Thomas Scheper
Wolfgang Meyer
Georgios Hadjigeorgiou
Dimitrios P. Bogdanos
Lazaros I. Sakkas
Publikationsdatum
26.01.2017
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 4/2017
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-017-3553-5

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