Advertisement

Immunologic Research

, Volume 64, Issue 3, pp 677–686 | Cite as

Heterogeneous clinical spectrum of anti-SRP myositis and importance of the methods of detection of anti-SRP autoantibodies: a multicentric study

  • Cécile Picard
  • Thierry Vincent
  • Jean-Christophe Lega
  • Sophie Hue
  • Françoise Fortenfant
  • Daniela Lakomy
  • René-Louis Humbel
  • Joelle Goetz
  • Nicolas Molinari
  • Nathalie Bardin
  • Daniel Bertin
  • Catherine Johanet
  • Pascale Chretien
  • Sylvain Dubucquoi
  • Nathalie Streichenberger
  • Sophie Desplat-Jégo
  • Xavier Bossuyt
  • Jean Sibilia
  • Isabelle Abreu
  • Alain Chevailler
  • Nicole FabienEmail author
Original Article

Abstract

Anti-signal recognition particle (SRP) antibodies are important serological markers for the diagnosis and the prognosis of idiopathic inflammatory myopathy (IIM), especially to distinguish immune-mediated necrotizing myopathy (IMNM). This study was set up to investigate the phenotype associated with anti-SRP antibodies and to evaluate the methods for detecting these antibodies. Clinical and biological data were retrospectively obtained from 60 adult patients with anti-SRP antibodies detected by a dot immunoassay from 12 centers. Thirty-six (60 %) out of these 60 patients suffered from an IIM, and among them, 21 patients were diagnosed as IMNM. Among patients with a definite IIM, proximal weakness and myalgia were prominent symptoms at the time of diagnosis. Only few patients displayed severe extra-muscular symptoms such as cardiac involvement or severe myositis. Mean creatine kinase levels were high for all patients except for two of them. When testing by indirect immunofluorescence (IIF) on HEp2 cells, the fraction of patients displaying the typical anti-SRP fine speckled staining of the cytoplasm was higher in patients with IIM (30/36) (83 %) than in patients with non-IIM (3/24) (12.5 %) (p < 0.0001). Thirty (91 %) out of 33 patients with a positive immunodot and a characteristic IIF cytoplasmic staining suffered from a clinical definite myositis, whereas only 6 (22 %) out of 27 patients with a positive immunodot but a negative cytoplasmic pattern suffered from a myositis (p < 0.00001). This series highlights the strong heterogeneity of anti-SRP positivity that encompassed IMNM and non-IMNM and supports the necessity of considering both IIF and dot immunoassay to confirm the diagnosis of anti-SRP-associated myositis.

Keywords

Anti-SRP antibodies Immune-mediated necrotizing myopathy Immunodot Indirect immunofluorescence 

Notes

Acknowledgments

We gratefully acknowledge the patients and the contributions made by the clinicians of all hospitals for the clinical data and especially: Pr JF Cordier JF, Pr. V. Cottin, Dr C. Khouatra, Dr J. Traclet, Pr J. Tebib, Pr J. Ninet, Dr G. Devouassoux, Dr B. Coppéré, Dr H. Gervais-Bernard, Dr E. Monard; Hospices Civils de Lyon; Dr C. Doche, CHG Chambéry, France; Pr J. Authier, neurology department, hôpital Henri Mondor, APHP, Créteil, France; Dr Steven Vanderschueren Catholic University of Leuven, University Hospitals Leuven; Belgique. We acknowledge Immunobiotec, CRB, HCL Lyon BB003300046.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004;14:337–45.CrossRefPubMedGoogle Scholar
  2. 2.
    Mammen AL. Necrotizing myopathies: beyond statins. Curr Opin Rheumatol. 2014;26:679–83.CrossRefPubMedGoogle Scholar
  3. 3.
    Miller T, Al-Lozi MT, Lopate G, Pestronk A. Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry. 2002;73:420–8.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Basnayake SK, Blumbergs P, Tan JA, Roberts-Thompson PJ, Limaye V. Inflammatory myopathy with anti-SRP antibodies: case series of a South Australian cohort. Clin Rheumatol. 2014;34:603–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Rider LG, Miller FW. Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies. JAMA. 2011;305:183–90.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Petiot P, Choumert A, Hamelin L, Devic P, Streichenberger N. Necrotizing autoimmune myopathies. Rev Neurol (Paris). 2013;169:650–5.CrossRefGoogle Scholar
  7. 7.
    Fernandez C, Bardin N, De Paula AM, Salort-Campana E, Benyamine A, Franques J, et al. Correlation of clinicoserologic and pathologic classifications of inflammatory myopathies: study of 178 cases and guidelines for diagnosis. Medicine (Baltimore). 2013;92:15–24.CrossRefGoogle Scholar
  8. 8.
    Valiyil R, Casciola-Rosen L, Hong G, Mammen A, Christopher-Stine L. Rituximab therapy for myopathy associated with anti-signal recognition particle antibodies: a case series. Arthritis Care Res (Hoboken). 2010;62:1328–34.CrossRefGoogle Scholar
  9. 9.
    Reeves WH, Nigam SK, Blobel G. Human autoantibodies reactive with the signal-recognition particle. Proc Natl Acad Sci USA. 1986;83:9507–11.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62:2757–66.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Benveniste O, Drouot L, Jouen F, Charuel JL, Bloch-Queyrat C, Behin A, et al. Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy. Arthritis Rheum. 2011;63:1961–71.CrossRefPubMedGoogle Scholar
  13. 13.
    Lega JC, Fabien N, Reynaud Q, Durieu I, Durupt S, Dutertre M, et al. The clinical phenotype associated with myositis-specific and associated autoantibodies: A meta-analysis revisiting the so-called antisynthetase syndrome. Autoimmun Rev. 2014;13:883–91.CrossRefPubMedGoogle Scholar
  14. 14.
    Hengstman GJ, ter Laak HJ, Vree Egberts WT, Lundberg IE, Moutsopoulos HM, Vencovsky J, et al. Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis. 2006;65:1635–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR, et al. Inclusion body myositis and myopathies. Ann Neurol. 1995;38:705–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Suzuki S, Nishikawa A, Kuwana M, Nishimura H, Watanabe Y, Nakahara J, et al. Inflammatory myopathy with anti-signal recognition particle antibodies: case series of 100 patients. Orphanet J Rare Dis. 2015;10:61.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372:1734–47.CrossRefPubMedGoogle Scholar
  18. 18.
    Hengstman GJ, Brouwer R, Egberts WT, Seelig HP, Jongen PJ, van Venrooij WJ, et al. Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific autoantibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol. 2002;249:69–75.CrossRefPubMedGoogle Scholar
  19. 19.
    Hirakata M, Mimori T, Akizuki M, Craft J, Hardin JA, Homma M. Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease. Arthritis Rheum. 1992;35:449–56.CrossRefPubMedGoogle Scholar
  20. 20.
    Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, et al. Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis. 2001;60:116–23.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Milisenda JC, Selva-O’Callaghan A, Grau JM. The diagnosis and classification of polymyositis. J Autoimmun. 2014;48–49:118–21.CrossRefPubMedGoogle Scholar
  22. 22.
    Ronnelid J, Barbasso Helmers S, Storfors H, Grip K, Ronnblom L, Franck-Larsson K, et al. Use of a commercial line blot assay as a screening test for autoantibodies in inflammatory myopathies. Autoimmun Rev. 2009;9:58–61.CrossRefPubMedGoogle Scholar
  23. 23.
    De Bleecker JL, De Paepe B, Aronica E, de Visser M, Amato A, Benveniste O, et al. 205th ENMC International Workshop: pathology diagnosis of idiopathic inflammatory myopathies part II 28-30 March 2014, Naarden, The Netherlands. Neuromuscul Disord. 2015;25:268–72.CrossRefPubMedGoogle Scholar
  24. 24.
    Targoff IN, Johnson AE, Miller FW. Antibody to signal recognition particle in polymyositis. Arthritis Rheum. 1990;33:1361–70.CrossRefPubMedGoogle Scholar
  25. 25.
    Troyanov Y, Targoff IN, Tremblay JL, Goulet JR, Raymond Y, Senecal JL. Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients. Medicine (Baltimore). 2005;84:231–49.CrossRefGoogle Scholar
  26. 26.
    Kao AH, Lacomis D, Lucas M, Fertig N, Oddis CV. Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum. 2004;50:209–15.CrossRefPubMedGoogle Scholar
  27. 27.
    Aggarwal R, Oddis CV, Goudeau D, Fertig N, Metes I, Stephens C, et al. Anti-signal recognition particle autoantibody ELISA validation and clinical associations. Rheumatology (Oxford). 2015;54:1194–9.CrossRefGoogle Scholar
  28. 28.
    Wang L, Liu L, Hao H, Gao F, Liu X, Wang Z, et al. Myopathy with anti-signal recognition particle antibodies: clinical and histopathological features in Chinese patients. Neuromuscul Disord. 2014;24:335–41.CrossRefPubMedGoogle Scholar
  29. 29.
    Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, et al. A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore). 1991;70:360–74.CrossRefGoogle Scholar
  30. 30.
    Dimitri D, Andre C, Roucoules J, Hosseini H, Humbel RL, Authier FJ. Myopathy associated with anti-signal recognition peptide antibodies: clinical heterogeneity contrasts with stereotyped histopathology. Muscle Nerve. 2007;35:389–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Arbuckle MR, McClain MT, Rubertone MV, Scofield RH, Dennis GJ, James JA, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526–33.CrossRefPubMedGoogle Scholar
  32. 32.
    Kokkonen H, Mullazehi M, Berglin E, Hallmans G, Wadell G, Ronnelid J, et al. Antibodies of IgG, IgA and IgM isotypes against cyclic citrullinated peptide precede the development of rheumatoid arthritis. Arthritis Res Ther. 2011;13:R13.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Cécile Picard
    • 1
  • Thierry Vincent
    • 2
    • 3
  • Jean-Christophe Lega
    • 4
  • Sophie Hue
    • 2
    • 5
  • Françoise Fortenfant
    • 2
    • 6
  • Daniela Lakomy
    • 2
    • 7
  • René-Louis Humbel
    • 2
    • 8
  • Joelle Goetz
    • 2
    • 9
  • Nicolas Molinari
    • 10
  • Nathalie Bardin
    • 2
    • 11
  • Daniel Bertin
    • 12
  • Catherine Johanet
    • 2
    • 13
  • Pascale Chretien
    • 2
    • 14
  • Sylvain Dubucquoi
    • 2
    • 15
  • Nathalie Streichenberger
    • 16
  • Sophie Desplat-Jégo
    • 2
    • 12
  • Xavier Bossuyt
    • 2
    • 17
    • 18
  • Jean Sibilia
    • 2
    • 19
  • Isabelle Abreu
    • 2
    • 20
  • Alain Chevailler
    • 2
    • 21
  • Nicole Fabien
    • 1
    • 2
    Email author
  1. 1.Department of Immunology, Centre Hospitalier Lyon-SudHospices Civils de LyonPierre-Benite CedexFrance
  2. 2.Groupe d’Etude de l’Auto-Immunité (GEAI)AngersFrance
  3. 3.Department of Immunology, St Eloi HospitalMontpellier University, CHRU de MontpellierMontpellier Cedex 5France
  4. 4.Department of Internal and Vascular Medicine, Centre Hospitalier Lyon-Sud, Hospices Civils de LyonUniversité Lyon-1Pierre-Benite CedexFrance
  5. 5.Department of ImmunologyCHU Henri Mondor - Service d’Immunologie BiologiqueCréteilFrance
  6. 6.Department of ImmunologyHôpital RangueilToulouse, Cedex 9France
  7. 7.Department of ImmunologyCHU DijonDijon, CedexFrance
  8. 8.Laboratoire Luxembourgeois d’Immuno-PathologieEsch-SuralzetteLuxembourg
  9. 9.Department of ImmunologyNouvel Hôpital CivilStrasbourgFrance
  10. 10.Department of Medical InformationCHU de Montpellier, UMR MisteaMontpellierFrance
  11. 11.Department of Biological Immunology, UMR-S 1076, Faculté de PharmacieLBM AP-HM et Aix-Marseille-UniversitéMarseilleFrance
  12. 12.Department of Biological Immunology, UMR CNRS/AMU 7259LBM AP-HM et Aix-Marseille-UniversitéMarseilleFrance
  13. 13.Department of Immunology, AP-HP hôpital Saint-Antoine, UFR 967, Faculté de medecineUniversité Pierre et Marie CurieParis Cedex 12France
  14. 14.Department of ImmunologyCHU BicetreKremlin BicêtreFrance
  15. 15.Department of ImmunologyUniv Lille Nord de FranceLilleFrance
  16. 16.Hôpital Cardiovasculaire et pneumologique, Hospices Civils de LyonBronFrance
  17. 17.Department of Microbiology and ImmunologyCatholic University of LeuvenLouvainBelgium
  18. 18.Department of Laboratory MedicineUniversity Hospitals LeuvenLouvainBelgium
  19. 19.Department of Rheumatology, Centre national de référence des maladies auto-immunes systémiques rares, CHU HautepierreUniversité de StrasbourgStrasbourgFrance
  20. 20.Departamento Universitário de ImunologiaUniversidade Nova de Lisboa - Faculdade de Ciências MédicasLisbonPortugal
  21. 21.Department of Immunology and AllergologyCHU Hôpital Larrey, Institut de Biologie en SantéAngers Cedex 9France

Personalised recommendations