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Published in: Clinical Rheumatology 11/2013

01-11-2013 | Original Article

Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity

Authors: Sladjana Andrejevic, Ivica Jeremic, Mirjana Sefik-Bukilica, Milos Nikolic, Biljana Stojimirovic, Branka Bonaci-Nikolic

Published in: Clinical Rheumatology | Issue 11/2013

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Abstract

We assessed the relationship between the serum levels of antibodies against double-stranded DNA (dsDNA), C1q, nucleosomes, histones, C3 and C4 complement components with one another, with organ involvement and overall disease activity in patients with systemic lupus erythematosus (SLE). One hundred seventy-five sera from 99 patients with SLE, 31 sera of patients with other connective tissue diseases, and 20 sera from healthy blood donors were tested. SLE disease activity was assessed by modified SLEDAI-2K (M-SLEDAI-2K), not including complement and anti-dsDNA descriptors. Anti-dsDNA antibodies were measured by indirect immunofluorescence on Crithidia luciliae (CLIFT), standard enzyme-linked immunosorbent assay (ELISA) and ELISA for high-avidity antibodies. The most significant risk factor for renal involvement were anti-C1q antibodies (OR = 3.88, p < 0.05), high-avidity anti-dsDNA antibodies for polyserositis (OR = 7.99, p < 0.01), anti-histone antibodies for joint involvement (OR = 2.75, p < 0.05), and low C3 for cytopenia (OR = 11.96, p < 0.001) and mucocutaneous lesions (OR = 3.32, p < 0.01). Multiple linear regression analysis showed that disease activity in SLE could be predicted by the levels of antibodies against dsDNA determined by standard (p < 0.05) and high-avidity (p < 0.001) ELISA, and inversely associated with concentration of C3 (p < 0.001). Using stepwise method, high-avidity anti-dsDNA antibodies were found to be in the closest association to M-SLEDAI-2K. Moreover, positive test for high-avidity anti-dsDNA antibodies appeared as an independent risk factor for moderately to severely active disease (M-SLEDAI-2K>5) (OR = 5.5, p < 0.01). The presence of high-avidity anti-dsDNA antibodies represented a risk for renal, joint, and most importantly for serosal involvement. Our results suggest that simple and reliable ELISA for high-avidity anti-dsDNA antibodies is the test of good clinical utility for the assessment of global SLE activity.
Literature
1.
go back to reference Kramers C, Hylkema MN, Vanbruggen MCJ, Vandelagemaat R, Dijkman HBPM, Assmann KJM, Smeenk RJT, Berden JHM (1994) Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular-basement-membrane in-vivo. J Clin Invest 94:568–577PubMedCrossRef Kramers C, Hylkema MN, Vanbruggen MCJ, Vandelagemaat R, Dijkman HBPM, Assmann KJM, Smeenk RJT, Berden JHM (1994) Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular-basement-membrane in-vivo. J Clin Invest 94:568–577PubMedCrossRef
3.
go back to reference Amoura Z, Koutouzov S, Piette JC (2000) The role of nucleosomes in lupus. Curr Opin Rheumatol 12:369–373PubMedCrossRef Amoura Z, Koutouzov S, Piette JC (2000) The role of nucleosomes in lupus. Curr Opin Rheumatol 12:369–373PubMedCrossRef
4.
go back to reference Viard JP, Choquette D, Chabre H, Slama FB, Primo J, Letrait M, Venot A, Jacob L (1992) Anti-histone reactivity in systemic lupus erythematosus sera: a disease activity index linked to the presence of DNA: anti-DNA immune complexes. Autoimmunity 12:61–68PubMedCrossRef Viard JP, Choquette D, Chabre H, Slama FB, Primo J, Letrait M, Venot A, Jacob L (1992) Anti-histone reactivity in systemic lupus erythematosus sera: a disease activity index linked to the presence of DNA: anti-DNA immune complexes. Autoimmunity 12:61–68PubMedCrossRef
5.
go back to reference Horák P, Heřmanová Z, Zadražil J, Ciferská H, Ordeltová M, Kusá L, Žurek M, Tichý T (2006) C1q complement component and antibodies reflect SLE activity and kidney involvement. Clin Rheumatol 25:532–536PubMedCrossRef Horák P, Heřmanová Z, Zadražil J, Ciferská H, Ordeltová M, Kusá L, Žurek M, Tichý T (2006) C1q complement component and antibodies reflect SLE activity and kidney involvement. Clin Rheumatol 25:532–536PubMedCrossRef
6.
go back to reference Mok CC, Ho LY, Leung HW, Wong LG (2010) Performance of anti-C1q, antinucleosome, and anti-dsDNA antibodies for detecting concurrent disease activity of systemic lupus erythematosus. Transl Res 156:320–325PubMedCrossRef Mok CC, Ho LY, Leung HW, Wong LG (2010) Performance of anti-C1q, antinucleosome, and anti-dsDNA antibodies for detecting concurrent disease activity of systemic lupus erythematosus. Transl Res 156:320–325PubMedCrossRef
7.
go back to reference Schiffer LE, Hussain N, Wang X, Huang W, Sinha J, Ramanujam M, Davidson A (2002) Lowering anti-dsDNA antibodies–what’s new? Lupus 11:885–894PubMedCrossRef Schiffer LE, Hussain N, Wang X, Huang W, Sinha J, Ramanujam M, Davidson A (2002) Lowering anti-dsDNA antibodies–what’s new? Lupus 11:885–894PubMedCrossRef
8.
go back to reference Isenberg D, Smeenk R (2002) Clinical laboratory assays for measuring anti-dsDNA antibodies. Where are we now? Lupus 11:797–800PubMedCrossRef Isenberg D, Smeenk R (2002) Clinical laboratory assays for measuring anti-dsDNA antibodies. Where are we now? Lupus 11:797–800PubMedCrossRef
9.
go back to reference Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rithfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rithfield NF, Schaller JG, Talal N, Winchester RJ (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRef
10.
go back to reference Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291PubMed
11.
go back to reference Villegas-Zambrano N, Martínez-Taboada VM, Bolívar A, San Martin M, Alvarez L, Marin MJ, López-Hoyos M (2009) Correlation between clinical activity and serological markers in a wide cohort of patients with systemic lupus erythematosus: an eight-year prospective study. Ann NY Acad Sci 1173:60–66PubMedCrossRef Villegas-Zambrano N, Martínez-Taboada VM, Bolívar A, San Martin M, Alvarez L, Marin MJ, López-Hoyos M (2009) Correlation between clinical activity and serological markers in a wide cohort of patients with systemic lupus erythematosus: an eight-year prospective study. Ann NY Acad Sci 1173:60–66PubMedCrossRef
12.
go back to reference Toubi E, Rosner I, Rozenbaum M, Kessel A, Golan TD (2000) The benefit of combining hydroxychloroquine and quinacrine in the treatment of SLE patients. Lupus 9:92–95PubMedCrossRef Toubi E, Rosner I, Rozenbaum M, Kessel A, Golan TD (2000) The benefit of combining hydroxychloroquine and quinacrine in the treatment of SLE patients. Lupus 9:92–95PubMedCrossRef
13.
go back to reference Min D-J, Kim S-J, Park S-H, Seo Y-I, Kang H-J, Kim W-U, Cho C-S, Kim H-Y (2002) Anti-nucleosome antibody: significance in lupus patients lacking anti-double-stranded DNA antibody. Clin Exp Rheum 20:13–18 Min D-J, Kim S-J, Park S-H, Seo Y-I, Kang H-J, Kim W-U, Cho C-S, Kim H-Y (2002) Anti-nucleosome antibody: significance in lupus patients lacking anti-double-stranded DNA antibody. Clin Exp Rheum 20:13–18
14.
go back to reference Petri M, Buyon J, Kim M (1999) Classification and definition of major flares in SLE clinical trials. Lupus 8:685–91PubMedCrossRef Petri M, Buyon J, Kim M (1999) Classification and definition of major flares in SLE clinical trials. Lupus 8:685–91PubMedCrossRef
15.
go back to reference Swaak AJ, Aarden LA, Statius van Eps LW, Feltkamp TE (1979) Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum 22:226–235PubMedCrossRef Swaak AJ, Aarden LA, Statius van Eps LW, Feltkamp TE (1979) Anti-dsDNA and complement profiles as prognostic guides in systemic lupus erythematosus. Arthritis Rheum 22:226–235PubMedCrossRef
16.
go back to reference Reveille JD (2004) Predictive value of autoantibodies for activity of systemic lupus erythematosus. Lupus 13:290–297PubMedCrossRef Reveille JD (2004) Predictive value of autoantibodies for activity of systemic lupus erythematosus. Lupus 13:290–297PubMedCrossRef
17.
go back to reference López-Hoyos M, Cabeza R, Martínez-Taboada VM, Crespo J, SanSegundo D, Blanco R, López-Escribano H, Peña M, Rodrigez-Valverde V (2005) Clinical disease activity and titers of anti-dsDNA antibodies measured by an automated immunofluorescence assay in patients with systemic lupus erythematosus. Lupus 14:505–509PubMedCrossRef López-Hoyos M, Cabeza R, Martínez-Taboada VM, Crespo J, SanSegundo D, Blanco R, López-Escribano H, Peña M, Rodrigez-Valverde V (2005) Clinical disease activity and titers of anti-dsDNA antibodies measured by an automated immunofluorescence assay in patients with systemic lupus erythematosus. Lupus 14:505–509PubMedCrossRef
18.
go back to reference Chen C-Y, Tseng H-M, Chen L-C, Tsao C-H, Kuo M-L, Ou L-S, Huang J-L (2003) Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients. Lupus 12:266–273PubMedCrossRef Chen C-Y, Tseng H-M, Chen L-C, Tsao C-H, Kuo M-L, Ou L-S, Huang J-L (2003) Use of a new fluorescence immunoassay to detect anti-dsDNA antibodies is more correlated with disease activity and complement than the ELISA method in SLE patients. Lupus 12:266–273PubMedCrossRef
19.
go back to reference Winfield JB, Faiferman I, Koffler D (1977) Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest 59:90–96PubMedCrossRef Winfield JB, Faiferman I, Koffler D (1977) Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest 59:90–96PubMedCrossRef
20.
go back to reference Villalta D, Romelli PB, Savina C, Bizzaro N, Tozzoli R, Tonutti E, Ghirardello A, Doria A (2003) Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring. Lupus 12:31–36PubMedCrossRef Villalta D, Romelli PB, Savina C, Bizzaro N, Tozzoli R, Tonutti E, Ghirardello A, Doria A (2003) Anti-dsDNA antibody avidity determination by a simple reliable ELISA method for SLE diagnosis and monitoring. Lupus 12:31–36PubMedCrossRef
21.
go back to reference Ghirardello A, Villalta D, Morozzi G et al (2011) Diagnostic accuracy of currently available anti-double-stranded DNA antibody assays. An Italian multicentre study. Clin Exp Rheum 29:50–56 Ghirardello A, Villalta D, Morozzi G et al (2011) Diagnostic accuracy of currently available anti-double-stranded DNA antibody assays. An Italian multicentre study. Clin Exp Rheum 29:50–56
22.
go back to reference Jaekel HP, Trabandt A, Grobe N, Werle E (2006) Anti-dsDNA antibody subtypes and anti-C1q antibodies: toward a more reliable diagnosis and monitoring of systemic lupus erythematosus and lupus nephritis. Lupus 15:335–345CrossRef Jaekel HP, Trabandt A, Grobe N, Werle E (2006) Anti-dsDNA antibody subtypes and anti-C1q antibodies: toward a more reliable diagnosis and monitoring of systemic lupus erythematosus and lupus nephritis. Lupus 15:335–345CrossRef
23.
go back to reference Kim KH, Han JY, Kim JM, Lee SW, Chung WT (2007) Clinical significance of ELISA positive and immunofluorescence negative anti-dsDNA antibody. Clin Chim Acta 380:182–185PubMedCrossRef Kim KH, Han JY, Kim JM, Lee SW, Chung WT (2007) Clinical significance of ELISA positive and immunofluorescence negative anti-dsDNA antibody. Clin Chim Acta 380:182–185PubMedCrossRef
24.
go back to reference Antico A, Platzgummer S, Bassetti D, Bizzaro N, Tozzoli R, Villalta D (2010) Diagnosing systemic lupus erythematosus: new-generation immunoassays for measurement of anti-dsDNA antibodies are an effective alternative to the Farr technique and the Crithidia luciliae immunofluorescence test. Lupus 19:906–912PubMedCrossRef Antico A, Platzgummer S, Bassetti D, Bizzaro N, Tozzoli R, Villalta D (2010) Diagnosing systemic lupus erythematosus: new-generation immunoassays for measurement of anti-dsDNA antibodies are an effective alternative to the Farr technique and the Crithidia luciliae immunofluorescence test. Lupus 19:906–912PubMedCrossRef
25.
go back to reference Fiegel F, Buhl A, Jaekel HP, Werle E, Schmolke M, Ollert M, Luppa PB (2010) Autoantibodies to double-stranded DNA—intermethod comparison between four commercial immunoassays and a research biosensor-based device. Lupus 19:957–964PubMedCrossRef Fiegel F, Buhl A, Jaekel HP, Werle E, Schmolke M, Ollert M, Luppa PB (2010) Autoantibodies to double-stranded DNA—intermethod comparison between four commercial immunoassays and a research biosensor-based device. Lupus 19:957–964PubMedCrossRef
26.
go back to reference Wasmuth J-C, Grün B, Homrighausen A, Spangler U (2004) ROC analysis comparison of three assays for the detection of antibodies against double-stranded DNA in serum for the diagnosis of systemic lupus erythematosus. Clin Chem 50:2169–2171PubMedCrossRef Wasmuth J-C, Grün B, Homrighausen A, Spangler U (2004) ROC analysis comparison of three assays for the detection of antibodies against double-stranded DNA in serum for the diagnosis of systemic lupus erythematosus. Clin Chem 50:2169–2171PubMedCrossRef
27.
go back to reference Saisoong S, Eiam-Ong S, Hanvivatvong O (2006) Correlations between antinucleosome antibodies and anti-double-stranded DNA antibodies, C3, C4, and clinical activity in lupus patients. Clin Exp Rheumatol 24:51–58PubMed Saisoong S, Eiam-Ong S, Hanvivatvong O (2006) Correlations between antinucleosome antibodies and anti-double-stranded DNA antibodies, C3, C4, and clinical activity in lupus patients. Clin Exp Rheumatol 24:51–58PubMed
28.
go back to reference Su Y, Jia RL, Han I, Li ZG (2007) Role of anti-nucleosome antibody in the diagnosis of systemic lupus erythematosus. Clin Immunol 122:115–120PubMedCrossRef Su Y, Jia RL, Han I, Li ZG (2007) Role of anti-nucleosome antibody in the diagnosis of systemic lupus erythematosus. Clin Immunol 122:115–120PubMedCrossRef
29.
go back to reference Ghirardello A, Doria A, Zampieri S, Tarricone E, Tozzoli R, Villalta D, Bizzaro N, Piccolo A, Gambari PF (2004) Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients. J Autoimmun 22:235–240PubMedCrossRef Ghirardello A, Doria A, Zampieri S, Tarricone E, Tozzoli R, Villalta D, Bizzaro N, Piccolo A, Gambari PF (2004) Antinucleosome antibodies in SLE: a two-year follow-up study of 101 patients. J Autoimmun 22:235–240PubMedCrossRef
30.
go back to reference Manson JJ, Ma A, Rogers P, Mason LJ, Berden JH, van der Vlag J, D’Cruz DP, Isenberg DA, Rahman A (2009) Relationship between anti-dsDNA, anti-nucleosome and anti-alpha-actinin antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res Ther 11:R154PubMedCrossRef Manson JJ, Ma A, Rogers P, Mason LJ, Berden JH, van der Vlag J, D’Cruz DP, Isenberg DA, Rahman A (2009) Relationship between anti-dsDNA, anti-nucleosome and anti-alpha-actinin antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res Ther 11:R154PubMedCrossRef
31.
go back to reference Shabana AA, El-Ghawet AE, Machaly SA, Abu Hashim EM (2009) Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus. Clin Rheumatol 28:673–678PubMedCrossRef Shabana AA, El-Ghawet AE, Machaly SA, Abu Hashim EM (2009) Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus. Clin Rheumatol 28:673–678PubMedCrossRef
32.
go back to reference Ravirajan CT, Rowse L, MacGowan JR, Isenberg DA (2001) An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: a cross-sectional study. Rheumatology (Oxford) 40:1405–1412CrossRef Ravirajan CT, Rowse L, MacGowan JR, Isenberg DA (2001) An analysis of clinical disease activity and nephritis-associated serum autoantibody profiles in patients with systemic lupus erythematosus: a cross-sectional study. Rheumatology (Oxford) 40:1405–1412CrossRef
33.
go back to reference Schett G, Smolen J, Zimmermman C, Hiesberger H, Hoefler E, Fournel S, Muller S, Rubin RL, Steiner G (2002) The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are highly specific marker for SLE associated with increased disease activity. Lupus 11:704–715PubMedCrossRef Schett G, Smolen J, Zimmermman C, Hiesberger H, Hoefler E, Fournel S, Muller S, Rubin RL, Steiner G (2002) The autoimmune response to chromatin antigens in systemic lupus erythematosus: autoantibodies against histone H1 are highly specific marker for SLE associated with increased disease activity. Lupus 11:704–715PubMedCrossRef
34.
go back to reference Nauta AJ, Trouw LA, Daha MR, Tijsma O, Nieuwland R, Schwaeble WJ, Gingras AR, Mantovani A, Hack EC, Roos A (2002) Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 32:1726–1736PubMedCrossRef Nauta AJ, Trouw LA, Daha MR, Tijsma O, Nieuwland R, Schwaeble WJ, Gingras AR, Mantovani A, Hack EC, Roos A (2002) Direct binding of C1q to apoptotic cells and cell blebs induces complement activation. Eur J Immunol 32:1726–1736PubMedCrossRef
35.
go back to reference Flierman R, Daha MR (2007) Pathogenic role of anti-C1q autoantibodies in the development of lupus nephritis—a hypothesis. Mol Immunol 44:133–138PubMedCrossRef Flierman R, Daha MR (2007) Pathogenic role of anti-C1q autoantibodies in the development of lupus nephritis—a hypothesis. Mol Immunol 44:133–138PubMedCrossRef
36.
go back to reference Trouw LA, Groeneveld TW, Seelen MA, Dujis JM, Bajema IM, Prins FA, Kishore U, Salant DJ, Verebeek JS, van Kooten C, Daha MR (2004) Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest 114:679–688PubMed Trouw LA, Groeneveld TW, Seelen MA, Dujis JM, Bajema IM, Prins FA, Kishore U, Salant DJ, Verebeek JS, van Kooten C, Daha MR (2004) Anti-C1q autoantibodies deposit in glomeruli but are only pathogenic in combination with glomerular C1q-containing immune complexes. J Clin Invest 114:679–688PubMed
37.
go back to reference Tsirogianni A, Pipi E, Soufleros K (2009) Relevance of anti-C1q autoantibodies to lupus nephritis. Ann NY Acad Sci 1173:243–251PubMedCrossRef Tsirogianni A, Pipi E, Soufleros K (2009) Relevance of anti-C1q autoantibodies to lupus nephritis. Ann NY Acad Sci 1173:243–251PubMedCrossRef
38.
go back to reference Oelzner P, Deliyska B, Fünfstück R, Hein G, Herrmann D, Stein G (2003) Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus—relationship with disease activity and renal involvement. Clin Rheumatol 22:271–278PubMedCrossRef Oelzner P, Deliyska B, Fünfstück R, Hein G, Herrmann D, Stein G (2003) Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus—relationship with disease activity and renal involvement. Clin Rheumatol 22:271–278PubMedCrossRef
39.
go back to reference O’Flynn J, Flierman R, van der Pol P, Rops A, Satchell SC, Mathieson PW, van Kooten C, van der Vlag J, Berden JH, Daha MR (2011) Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for autoantibodies and determine complement activation. Mol Immunol 49:75–83PubMedCrossRef O’Flynn J, Flierman R, van der Pol P, Rops A, Satchell SC, Mathieson PW, van Kooten C, van der Vlag J, Berden JH, Daha MR (2011) Nucleosomes and C1q bound to glomerular endothelial cells serve as targets for autoantibodies and determine complement activation. Mol Immunol 49:75–83PubMedCrossRef
40.
go back to reference Mayer OC, Nicaise-Roland P, Cadoudal N, Grootenboer-Mignot S, Palazzo E, Hayem G, Dieudé P, Chollet-Martin S (2009) Anti-C1q antibodies antedate patient active glomerulonephritis in patients with systemic lupus erythematosus. Arthritis Res Ter 11:R87CrossRef Mayer OC, Nicaise-Roland P, Cadoudal N, Grootenboer-Mignot S, Palazzo E, Hayem G, Dieudé P, Chollet-Martin S (2009) Anti-C1q antibodies antedate patient active glomerulonephritis in patients with systemic lupus erythematosus. Arthritis Res Ter 11:R87CrossRef
41.
go back to reference Kavanaugh AF, Solomon DH (2002) Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-DNA antibody tests. Arthritis Rheum (Arthritis Care and Research) 47:546–555CrossRef Kavanaugh AF, Solomon DH (2002) Guidelines for immunologic laboratory testing in the rheumatic diseases: anti-DNA antibody tests. Arthritis Rheum (Arthritis Care and Research) 47:546–555CrossRef
Metadata
Title
Immunoserological parameters in SLE: high-avidity anti-dsDNA detected by ELISA are the most closely associated with the disease activity
Authors
Sladjana Andrejevic
Ivica Jeremic
Mirjana Sefik-Bukilica
Milos Nikolic
Biljana Stojimirovic
Branka Bonaci-Nikolic
Publication date
01-11-2013
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 11/2013
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-013-2330-3

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