PANEL 555

Inflammatory Myopathies (Myositis) without ANA and ENA screen

Indication

Suspicion of inflammatory myopathies, myositis (polymyositis - PM, dermatomyositis - DM, overlap syndrome, inclusion body myositis - IBM or immune-mediated necrotizing myopathy - IMNM).

Clinical background

Idiopathic inflammatory myopathies (myositis) constitute a heterogeneous group of diseases of which many have a presumed autoimmune origin. Dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM) are the main representatives of this group including the anti-synthetase syndrom. Myositis can also be seen in association with rheumatic disorders. Myositis is most often characterized by muscle weakness but involvement of joints, skin and lungs may also occur and even dominate the clinical picture. An elevation of creatine kinase in blood is a typical laboratory finding but can be discrete.

The diseases are in some cases considered immune mediated by infiltration of T-cells in the affected tissue while others are dominated by humoral immunity and/or activation of macrophages. In recent years, several autoantibodies have been identified as useful markers for subtypes of myositis. This is of great importance for diagnosing as well as prognosing and choosing optimal therapy. Myositis can be associated with underlying cancer (i. e. paraneoplastic origin) and occur years before the tumor is diagnostically detectable. Myositis-specific autoantibodies are directed against cytoplasmic or nuclear components involved in key regulatory intracellular processes such as protein synthesis and gene transcription.

Myositis-specific autoantibodies (MSAs): Jo-1 (Histidyl-tRNA-Synthetase), PL-7 (Threonyl-tRNA-Synthetase), PL-12 (Alanyl-tRNA-Synthetase), EJ (Glycyl-tRNA-Synthetase), OJ (Isoleucyl-tRNA-Synthetase), Mi-2, SRP (Signal Recognition Particle), KS (Asparaginyl-tRNA-Synthetase), TIF1γ/α, TIF1β, MJ/NXP2, MDA5/CADM140, SAE (SUMO-1)

Myositis-associated autoantibodies (MAAs): PM-Scl75, PM-Scl100, Ku, U1RNP, U1/U2RNP, U3RNP

Other autoantibodies often found in myositis: Ro52, Ro60, Su/Ago2.

Fig.1 Overview of the association of MSAs with the spectrum of muscle and skin involvements in different subsets of PM/DM. It varies from muscle disease without skin disease (PM), involvement of both muscle and skin with different degree of each (DM) to skin disease with minimal muscle involvement (CADM), or no muscle involvement (ADM). Anti-ARS (aminoacyl tRNA synthetase) is detected in both PM and DM and occasionally in ADM. Figure from Satoh M. et al. Clinic Rev Allerg Immunol (2017) 52:1-19. PMID: 26424665.

References

  • Satoh M. et al. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy, Clinic Rev Allerg Immunol (2017) 52:1-19. PMID: 26424665
  • Fujimoto M et al. Recent advances in dermatomyositis-specific autoantibodies. Curr Opin Rheumatol. 2016 Nov;28(6):636-44. PMID: 27533321
  • Nakashima R Et al. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease, Lupus (2016) 25, 925-933. PMID: 27252271
  • Trallero Arguas E et al. Semin Arthritis Rheum. Clinical manifestations and long-term outcome of anti-Jo1 antisynthetase patients in a large cohort of Spanish patients from the GEAS-IIM group. 2016 Oct;46(2):225-31. PMID: 27139168
  • Allenbach Y, Benveniste O. Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases, Journal of Neuromuscular Diseases 2 (2015) 13-25. PMID: 28198709
  • Ghirardello A. et al. Myositis autoantibodies and clinical phenotypes, Autoimmun Highlights (2014) 5:69-7. PMID: 26000158
  • Beneviste et al, Arthritis Rheum 2011;63(7):1961. Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy. PMID: 21400483 (SRP artikel)
  • Belizna C. et al. Anti-Ku antibodies: Clinical, genetic and diagnostic insights. Autoimmunity Reviews 2010;9:691. PMID: 20621654 (bra översiktsartikel om anti-Ku)
  • Gunawardena H, Betteridge ZE, McHugh NJ. Myositis-specific autoantibodies: their clinical and pathogenic significance in disease expression, Rheumatology 2009;48:607-612. PMID: 19439503
  • Mahler M et al. Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmunity Reviews 2007;6:432. PMID: 17643929 (bra översiktsartikel om anti-PM-Scl)

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Autoimmune diagnostics
Neurology

PAKET 555

Inflammatoriska Myopatier (Myositer) utan ANA och ENA

Indikation

Misstanke om inflammatoriska myopatier, myositer (polymyosit - PM, dermatomyosit - DM, overlap syndrom, inklusionskroppsmyosit - IBM eller immunmedierade nekrotiserande myopati - IMNM).

Klinik

Idiopatiska inflammatoriska myopatier utgör ett spektrum av inflammatoriska sjukdomar med förmodad autoimmun genes. De mest väldefinierade diagnosgrupperna utgörs av polymyosit (PM), dermatomyosit (DM), inklusionskroppsmyosit (IBM), immunmedierad nekrotiserande myopati och olika varianter av anti-syntetas-syndrom. Myosit kan också vara del av vissa reumatiska sjukdomar. I första hand drabbas muskelvävnad, men även leder, hud och lungor kan involveras och dominera sjukdomsbilden. Muskelsvaghet är ett vanligt debutsymtom, men i vissa fall kan muskelsymtom vara mycket diskreta eller t.o.m. saknas. CK (creatine kinase)-stegring är typiskt men kan vara diskret.

Sjukdomarna betraktas som immunmedierade med infiltration av T-celler i den drabbade vävnaden i vissa fall medan andra domineras av humoral immunitet och/eller aktivering av makrofager. På senare år har flera autoantikroppsspecificiteter identifierats och utgör viktiga diagnostiska redskap för att identifiera olika varianter av dessa sjukdomar. Detta är viktigt ur såväl ett diagnostiskt som ett behandlings- och prognostiskt perspektiv. Vissa av subtyperna är starkt associerade med bakomliggande malignitet och kan föregå malignitet med flera år. Myosit-relaterade autoantikroppar är riktade mot olika cellulära proteiner som är involverade i olika intracellulära processer som t.ex. proteinsyntes och transkription.

Myosit-specifika autoantikroppar: Jo-1 (Histidyl-tRNA-Synthetase), PL-7 (Threonyl-tRNA-Synthetase), PL-12 (Alanyl-tRNA-Synthetase), EJ (Glycyl-tRNA-Synthetase), OJ (Isoleucyl-tRNA-Synthetase), Mi-2, SRP (Signal Recognition Particle), KS (Asparaginyl-tRNA-Synthetase), TIF1γ/α, TIF1β, MJ/NXP2, MDA5/CADM140, SAE (SUMO-1)

Myosit-associerade autoantikroppar: PM-Scl75, PM-Scl100, Ku, U1RNP, U1/U2RNP, U3RNP

Andra autoantikroppsspecificiteter som ofta påvisas vid myosit: Ro52, Ro60, Su/Ago2



Fig. 1 Översikt över associeringen av Myosit-specifika autoantikroppar med spektrumet av muskel- och hud-involveringar i olika typer av PM / DM. Det varierar från muskelsjukdomar utan hudsjukdom (PM), inblandning av både muskler och hud med olika grader av varje (DM) mot hudsjukdomar med minimalt muskelpåverkan (CADM) eller ingen muskelpåverkan (ADM). Anti-ARS (aminoacyl-tRNA-syntetas) detekteras i både PM och DM och ibland i ADM. Figur från Satoh M. et al. Clinic Rev Allerg Immunol (2017) 52:1-19. PMID: 26424665

References

Satoh M. et al. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy, Clinic Rev Allerg Immunol (2017) 52:1-19. PMID: 26424665

Fujimoto M et al. Recent advances in dermatomyositis-specific autoantibodies. Curr Opin Rheumatol. 2016 Nov;28(6):636-44. PMID: 27533321

Nakashima R Et al. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease, Lupus (2016) 25, 925-933. PMID: 27252271

Trallero Arguas E et al. Semin Arthritis Rheum. Clinical manifestations and long-term outcome of anti-Jo1 antisynthetase patients in a large cohort of Spanish patients from the GEAS-IIM group. 2016 Oct;46(2):225-31. PMID: 27139168

Allenbach Y, Benveniste O. Diagnostic Utility of Auto-Antibodies in Inflammatory Muscle Diseases, Journal of Neuromuscular Diseases 2 (2015) 13-25. PMID: 28198709

Ghirardello A. et al. Myositis autoantibodies and clinical phenotypes, Autoimmun Highlights (2014) 5:69-7. PMID: 26000158

Beneviste et al, Arthritis Rheum 2011;63(7):1961. Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy. PMID: 21400483 (SRP artikel)

Belizna C. et al. Anti-Ku antibodies: Clinical, genetic and diagnostic insights. Autoimmunity Reviews 2010;9:691. PMID: 20621654 (bra översiktsartikel om anti-Ku)

Gunawardena H, Betteridge ZE, McHugh NJ. Myositis-specific autoantibodies: their clinical and pathogenic significance in disease expression, Rheumatology 2009;48:607-612. PMID: 19439503

Mahler M et al. Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmunity Reviews 2007;6:432. PMID: 17643929 (bra översiktsartikel om anti-PM-Scl)

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Autoimmun diagnostik
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