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Open Access 01-02-2009 | Research article

Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients

Authors: Katharina Hanke, Claudia S Brückner, Cornelia Dähnrich, Dörte Huscher, Lars Komorowski, Wolfgang Meyer, Anthonia Janssen, Marina Backhaus, Mike Becker, Angela Kill, Karl Egerer, Gerd R Burmester, Falk Hiepe, Wolfgang Schlumberger, Gabriela Riemekasten

Published in: Arthritis Research & Therapy | Issue 1/2009

Abstract

Introduction

Anti-PM/Scl antibodies are present in sera from patients with polymyositis (PM), systemic sclerosis (SSc), and PM/SSc overlap syndromes. The prevalence of antibodies against the 75- and 100-kDa PM/Scl proteins and their clinical associations have not been studied in SSc patients in detail so far but could provide a valuable tool for risk assessment in these patients. Furthermore, it remains speculative whether commercially available test systems detecting only anti-PM/Scl-100 antibodies are sufficient in SSc patients.

Methods

Two hundred eighty sera from SSc patients, patients with other connective tissue diseases (n = 209), and healthy blood donors (n = 50) were analyzed for the presence of anti-PM/Scl-75 and anti-PM/Scl-100 antibodies by means of line immunoblot assay. For the SSc patients, possible associations between both subsets of anti-PM/Scl antibodies with clinical and laboratory findings were studied.

Results

The determination of anti-PM/Scl reactivity revealed a diagnostic sensitivity of 12.5% and a specificity of 96.9% for SSc. Among anti-PM/Scl-positive SSc patients, 10.4% and 7.1% were positive for anti-PM/Scl-75 and anti-PM/Scl-100 antibodies, respectively. The highest prevalences of reactivity to PM/Scl were detected in diffuse SSc (19.8%) and overlap syndromes (17.6%). Patients with diffuse SSc showed mainly an anti-PM/Scl-75 response, whereas most cases of overlap syndromes were characterized by reactivity to both PM/Scl antigens. The presence of anti-PM/Scl-75/100 antibodies was associated with muscular and lung involvements as well as with digital ulcers; pulmonary arterial hypertension was found less frequently. Anti-PM/Scl-75 antibodies were detected more frequently in younger and more active patients with joint contractures. Anti-PM/Scl-100 antibodies were associated with creatine kinase elevation; however, gastrointestinal involvements were observed less frequently.

Conclusions

Anti-PM/Scl antibodies are common in distinct SSc subsets and are associated with several clinical symptoms. They are directed mainly to the PM/Scl-75 antigen. Consequently, the detection of anti-PM/Scl antibodies by tests based only on PM/Scl-100 as an antigen source may miss a relevant number of SSc patients positive for these antibodies.

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Reichlin M, Maddison PJ, Targoff I, Bunch T, Arnett F, Sharp G, Treadwell E, Tan EM: Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes. J Clin Immunol. 1984, 4: 40-44. 10.1007/BF00915286.CrossRefPubMed

Steen VD: Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005, 35: 35-42. 10.1016/j.semarthrit.2005.03.005.CrossRefPubMed

Mahler M, Raijmakers R: Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmun Rev. 2007, 6: 432-437. 10.1016/j.autrev.2007.01.013.CrossRefPubMed

Oddis CV, Okano Y, Rudert WA, Trucco M, Duquesnoy RJ, Medsger TA: Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations. Arthritis Rheum. 1992, 35: 1211-1217. 10.1002/art.1780351014.CrossRefPubMed

Marguerie C, Bunn CC, Copier J, Bernstein RM, Gilroy JM, Black CM, So AK, Walport MJ: The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. Medicine (Baltimore). 1992, 71: 327-336. 10.1097/00005792-199211000-00001.CrossRef

Vandergheynst F, Ocmant A, Sordet C, Humbel RL, Goetz J, Roufosse F, Cogan E, Sibilia J: Anti-pm/scl antibodies in connective tissue disease: clinical and biological assessment of 14 patients. Clin Exp Rheumatol. 2006, 24: 129-133.PubMed

Alderuccio F, Chan EK, Tan EM: Molecular characterization of an autoantigen of PM-Scl in the polymyositis/scleroderma overlap syndrome: a unique and complete human cDNA encoding an apparent 75-kD acidic protein of the nucleolar complex. J Exp Med. 1991, 173: 941-952. 10.1084/jem.173.4.941.CrossRefPubMed

Blüthner M, Bautz FA: Cloning and characterization of the cDNA coding for a polymyositis-scleroderma overlap syndrome-related nucleolar 100-kD protein. J Exp Med. 1992, 176: 973-980. 10.1084/jem.176.4.973.CrossRefPubMed

Raijmakers R, Renz M, Wiemann C, Egberts WV, Seelig HP, van Venrooij WJ, Pruijn GJ: PM-Scl-75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome. Arthritis Rheum. 2004, 50: 565-569. 10.1002/art.20056.CrossRefPubMed

10.

Raijmakers R, Egberts WV, van Venrooij WJ, Pruijn GJ: The association of the human PM/Scl-75 autoantigen with the exosome is dependent on a newly identified N terminus. J Biol Chem. 2003, 278: 30698-30704. 10.1074/jbc.M302488200.CrossRefPubMed

11.

Mahler M, Raijmakers R, Dähnrich C, Blüthner M, Fritzler MJ: Clinical evaluation of autoantibodies to a novel PM/Scl peptide antigen. Arthritis Res Ther. 2005, 7: R704-713. 10.1186/ar1729.PubMedCentralCrossRefPubMed

12.

Hanke K, Dahnrich C, Bruckner C, Huscher D, Becker M, Janssen A, Meyer W, Egerer K, Hiepe F, Burmester G R, Schlumberger W, Riemekasten G: Diagnostic value of anti-topoisomerase I antibodies in a large monocentric cohort. Arthritis Res Ther. 2009, 11: R28-10.1186/ar2622.PubMedCentralCrossRefPubMed

13.

Walker UA, Tyndall A, Czirják L, Denton C, Farge-Bancel D, Kowal-Bielecka O, Müller-Ladner U, Bocelli-Tyndall C, Matucci-Cerinic M: Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Ann Rheum Dis. 2007, 66: 754-763. 10.1136/ard.2006.062901.PubMedCentralCrossRefPubMed

14.

Hunzelmann N, Genth E, Krieg T, Lehmacher W, Melchers I, Meurer M, Moinzadeh P, Müller-Ladner U, Pfeiffer C, Riemekasten G, Schulze-Lohoff E, Sunderkoetter C, Weber M, Worm M, Klaus P, Rubbert A, Steinbrink K, Grundt B, Hein R, Scharffetter-Kochanek K, Hinrichs R, Walker K, Szeimies RM, Karrer S, Müller A, Seitz C, Schmidt E, Lehmann P, Foeldvári I, Reichenberger F, et al: Registry of the German Network for Systemic Scleroderma. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford). 2008, 47: 1185-1192. 10.1093/rheumatology/ken179.CrossRef

15.

Czirják L, Nagy Z, Aringer M, Riemekasten G, Matucci-Cerinic M, Furst DE, EUSTAR: The EUSTAR model for teaching and implementing the modified Rodnan skin score in systemic sclerosis. Ann Rheum Dis. 2007, 66: 966-969. 10.1136/ard.2006.066530.PubMedCentralCrossRefPubMed

16.

LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988, 15: 202-205.PubMed

17.

Bennett RM: Scleroderma overlap syndrome. Rheum Dis Clin North Am. 1990, 16: 185-198.PubMed

18.

Rodnan GP, Fennel RH: Progressive systemic sclerosis sine scleroderma. JAMA. 1962, 180: 665-670.CrossRefPubMed

19.

Mosca M, Neri R, Bombardieri S: Undifferentiated connective tissue diseases (UCTD): a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol. 1999, 17: 615-620.PubMed

20.

Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB, Braga S, Coll J, de Vita S, Drosos AA, Ehrenfeld M, Hatron PY, Hay EM, Isenberg DA, Janin A, Kalden JR, Kater L, Konttinen YT, Maddison PJ, Maini RN, Manthorpe R, Meyer O, Ostuni P, Pennec Y, Prause JU, Richards A, Sauvezie B, Schiødt M, Sciuto M, et al: Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993, 36: 340-347. 10.1002/art.1780360309.CrossRefPubMed

21.

Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982, 25: 1271-1277. 10.1002/art.1780251101.CrossRefPubMed

22.

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002/art.1780310302.CrossRefPubMed

23.

Furst DE, Clements PJ, Steen VD, Medsger TA, Masi AT, D'Angelo WA, Lachenbruch PA, Grau RG, Seibold JR: The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis. J Rheumatol. 1998, 25: 84-88.PubMed

24.

Valentini G, Bencivelli W, Bombardieri S, D'Angelo S, Della Rossa A, Silman AJ, Black CM, Czirjak L, Nielsen H, Vlachoyiannopoulos PG: European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria. Ann Rheum Dis. 2003, 62: 901-903. 10.1136/ard.62.9.901.PubMedCentralCrossRefPubMed

25.

Blüthner M, Mahler M, Müller DB, Dünzl H, Bautz FA: Identification of an alpha-helical epitope region on the PM/Scl-100 autoantigen with structural homology to a region on the heterochromatin p25beta autoantigen using immobilized overlapping synthetic peptides. J Mol Med. 2000, 78: 47-54. 10.1007/s001090050381.CrossRefPubMed

26.

Selva-O'Callaghan A, Labrador-Horrillo M, Solans-Laque R, Simeon-Aznar CP, Martínez-Gómez X, Vilardell-Tarrés M: Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy. Arthritis Rheum. 2006, 55: 791-798. 10.1002/art.22237.CrossRefPubMed

27.

Brouwer R, Vree Egberts WT, Hengstman GJ, Raijmakers R, van Engelen BG, Seelig HP, Renz M, Mierau R, Genth E, Pruijn GJ, van Venrooij WJ: Autoantibodies directed to novel components of the PM/Scl complex, the human exosome. Arthritis Res. 2002, 4: 134-138. 10.1186/ar389.PubMedCentralCrossRefPubMed

28.

Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, Grøndal G, Hietarinta M, Isenberg D, Kalden JR, Lundberg I, Moutsopoulos H, Roux-Lombard P, Vencovsky J, Wikman A, Seelig HP, van Engelen BG, van Venrooij WJ: Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001, 60: 116-123. 10.1136/ard.60.2.116.PubMedCentralCrossRefPubMed

29.

Mahler M, Mierau R, Humbel RL, Fritzler MJ: Anti-PM1-alpha antibodies: analytical evaluation in two centers. Paper presented at: 6th International Congress on Autoimmunity; 10–14 September 2008; Porto, Portugal

30.

Schmidt M, Hoffman DR: Expression systems for production of recombinant allergens. Int Arch Allergy Immunol. 2002, 128: 264-270. 10.1159/000063865.CrossRefPubMed

31.

Hu YC: Baculovirus as a highly efficient expression vector in insect and mammalian cells. Acta Pharmacol Sin. 2005, 26: 405-416. 10.1111/j.1745-7254.2005.00078.x. ReviewCrossRefPubMed

Title: Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients
Authors: Katharina Hanke
Claudia S Brückner
Cornelia Dähnrich
Dörte Huscher
Lars Komorowski
Wolfgang Meyer
Anthonia Janssen
Marina Backhaus
Mike Becker
Angela Kill
Karl Egerer
Gerd R Burmester
Falk Hiepe
Wolfgang Schlumberger
Gabriela Riemekasten
Publication date: 01-02-2009
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2009
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar2614

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Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients

Abstract

Introduction

Methods

Results

Conclusions

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Abstract

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