Muscle inflammatory processes and their clinical manifestations in patients with polymyositis and dermatomyositis


Authors: J. Tomasová Studýnková
Authors‘ workplace: Revmatologický ústav, Praha
Published in: Čes. Revmatol., 15, 2007, No. 1, p. 34-46.
Category: Summaries of Doctoral Dissertations

Overview

Idiopathic inflammatory myopathies (IIM) include dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM), which are clinically characterized by symmetrical proximal muscle weakness. The etiology and pathogenesis are unknown although immunological mechanisms appear to be involved. The hallmark and the basic histopathological criterion is an infiltrate with inflammatory cells. This muscle inflammation is often focal and heterogeneous. Not all of the muscles are affected at the same time with the same patient. Cases with persistent muscle weakness exist while at the same time the inflammatory infiltrate is only minimal or can no longer be found. The cause of the weakness appears to be largely unknown. The aim of our project was to find out and describe mechanisms that lead to the infiltration of inflammatory cells in the muscle tissue, muscle edema and the tissue damage, and subsequently to the clinical symptoms in patients with PM and DM. There is not much known about the factors that contribute to the persistence of inflammatory cells in muscle tissues and for the formation of edema in the muscle tissue. We searched for the contribution of COX and LOX enzymes production in the muscle during the evolution of myositis to understand the role that COX, LOX and their products might play in the pathogenesis of this disease. We observed for the first time the expression of COX-1, COX-2 and 5-LOX mRNA in muscle tissues from IIM patients. This expression of mRNA for these enzymes was increased in affected tissues and this was seen not only in inflammatory or vascular cells but also in muscle cells. The fact that COX and LOX enzymes are induced in myositis suggests their contribution to pathologic processes during the disease. The expression of IP-10-CXCR3 system in the muscle tissue samples points towards significant participation in the disease pathogenesis. The fact that CCR5 is not present in the infiltrating cells shows small representation of Th1 cells and it attributes the reaction between IP-10 and CXCR3 the role rather in activation of the muscle cells. The reason for hyperexpression of HLA class I molecules can be constituted by frequent expression of IFN-β. Acute inflammation in IIM causes edema that can be visualized by magnetic resonance imaging (MRI). The inflammatory infiltrate in IIM is thought to be frequent in a focal distribution. We tried to better evaluate the relationship of MR image of thigh muscles to clinical and histological parameters in patients with IIM. Assessment of the global and muscle disease activity correlated best with the intensity of MR image. Biopsies guided by positive MRI findings detect significantly more inflammatory infiltrate than the biopsies taken from MRI non-affected sites. The intensity of MRI oedema decreased significantly after the treatment, however, the improvement in the histologically detected inflammation has not been seen. This suggests that MRI could be a preferable parameter to histology in evaluation of clinical status and treatment effect in PM and DM patients. In our clinical study we attempted to determine the effectiveness and tolerance of treatment with cyclosporine A (CyA) or methotrexate (MTX) added to corticosteroids in patients with severe, active PM and DM. Significant improvement in muscle endurance and functional test (MEFT), clinical assessment (CA), global patient’s assessment (GPA) and muscle MRI was found in both groups MTX and CyA. Patients treated with MTX showed insignificantly better response than patients with CyA. CK levels in MTX group decreased significantly after 1, 3 and 6 months, whereas significant reduction in CyA group was first observed after 6 months. IL-1Ra serum levels significantly dropped in CyA group after two weeks, whereas in MTX group the significant decrease was first seen after 3 months of treatment. Good correlation was found between each of the clinical parameters (MEFT, CA and GPA), none of them showed any correlation with CK or IL-1Ra levels. Administration of MTX or CyA added to corticosteroids was associated with clinical and laboratory improvement. Changes in CK and IL-1Ra levels were not associated with parameters of clinical disease severity measured in this study.


Sources

1. Bohan A, Peter JB. Polymyositis and dermatomyositis (First of two parts). N Engl J Med 1975; 292: 344–347.

2. Bohan A, Peter JB. Polymyositis and dermatomyositis (Second of two parts). N Engl J Med 1975; 292: 403–407.

3. Dalakas M. Polymyositis, dermatomyositis, and inclusion body myositis. N Engl J Med 1991; 325: 1487–98.

4. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet 2003; 362: 71–82.

5. Nagaraju K. Update on immunopathogenesis in inflammatory myopathies. Curr Opin Rheumatol 2001; 13: 461–8.

6. Lundberg I, Kratz AK, Alexanderson H, Patarroyo M. Decreased expression of interleukin-1alpha, interleukin-1beta, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis. Arthritis Rheum 2000; 43(2): 336–48.

7. Hohlfeld R, Engel AG, Goebels N, Behrens L. Cellular immune mechanisms in inflammatory myopathies. Curr Opin Rheumatol 1997; 9: 520–6.

8. Messner RP. Pathogenesis of Idiopathic Inflammatory Myopathies. Diseases of Sceletal Muscle. Edited by Wortmann RL. Philadelphia, Lippincott Williams & Wilkins, 2000, 111–128.

9. Englund P, Lindroos E, Nennesmo I, Klareskog L, Lundberg IE. Skeletal muscle fibers express major histocompatibility complex class II antigens independently of inflammatory infiltrates in inflammatory myopathies. Am J Pathol 2001; 159: 1263–73.

10. Nyberg P, Wikman AL, Nennesmo I, Lundberg I. Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis. J Rheumatol 2000; 27: 940–8.

11. Inukai A, Kuru S, Liang Y, et al. Expression of HLA–DR and its enhancing molecules in muscle fibers in polymyositis. Muscle Nerve 2000; 23: 385–92.

12. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001; 294: 1871–5.

13. Smith WL, Garavito RM, De Witt DL. Prostaglandin endoperoxide H synthase (cyclooxygenase)-1 and –J Biol Chem 1996; 271: 33157–60.

14. Parker CW. Leukotrienes and prostaglandins in the immune system. Adv Prostaglandin Thromboxane Leukot Res 1986; 16: 113–34.

15. Smith WL, Langenbach R. Why there are two cyclooxygenase isozymes. J Clin Invest 2001; 107: 1491–5.

16. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063–73.

17. Crofford LJ. COX-1 and COX-2 tissue expression: implications and predictions. J Rheum 1997;24:S15–19.

18. Pablos JL, Santiago B, Carreira PE, Galindo M, Gomez-Reino JJ. Cyclooxygenase-1 and -2 are expressed by human T cells. Clin Exp Immunol 1999; 115: 86–90.

19. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 1990;323:645–55.

20. Rocca B, Spain LM, Pure E, Langenbach R, Patrono C, FitzGerald GA. Distinct roles of prostaglandin H synthases 1 and 2 in T-cell development. J Clin Invest 1999; 103: 1469–77.

21. Sheng H, Shao J, Morow JD, Beauchamp RD, DuBois RN. Modulation of apoptosis and Bcl-2 expression prostaglandin E2 in human colon cancer cells. Cancer Res 1998; 58: 362–6.

22. Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 1997;367:620–4.

23. Szekanecz Z, Szucs G, Szanto S, Koch AE. Chemokines in rheumatic diseases. Curr Drug Targets. 2006;7(1):91–102.

24. Rollins BJ. Chemokines. Blood 1997; 90: 909–28.

25. Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines-CXC and CC chemokines. Adv Immunol 1994;55:97–179.

26. Narumi S, Takeuchi T, Kobayashi Y, Konishi K. Serum levels of IFN-inducible protein-10 relating to the activity of systemic lupus erythematosus. Cytokine 2000; 12: 1561–5.

27. Loetscher M, Gerber B, Loetscher P, et al. Chemokine receptor specific for IP1O and Mig: structure, function and expression in activated T lymphocytes. J Exp Med 1996; 184: 963–9.

28. Confalonieri P, Bernasconi P, Megna P, Galbiati S, Cornelio F, Mantegazza R. Increased expression of beta-chemokines in muscle of patients with inflammatory myopathies. J Neuropathol Exp Neurol 2000; 59: 164–169.

29. Adams EM, Kirkley J, Eidelman G, Dohlman J, Plotz PH. The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory muscle diseases. Proc Assoc Am Physicians. 1997; 109(3): 275–85.

30. Goldberg SH, van der Meer P, Hesselgesser J, et al. CXCR3 expression in human central nervous systém diseases. Neuropathol Appl Neurobiol 2001; 27: 127–38.

31. Doly J, Civas A, Navarro S, Uze G. Type I interferons: expression and signalization. Cell Mol Life Sci 1998; 54:1109–21.

32. Young VW, Chabot S, Stuve O, Williams G. Interferon beta in the treatment of multiple sclerosis. Mechanisms of action. Neurology 1998;51:682–9.

33. Jungo F, Dayer JM, Modoux C, Hyka N, Burger D. IFN-beta inhibits the ability of T lymphocytes to induce TNF-alpha and IL-1beta production in monocytes upon direct cell-cell contact. Cytokine 2001; 14: 272–82.

34. Ossege LM, Sindern E, Patzold T, Malin J-P. Immunomodulatory effects of interferon-beta-1b in vivo: induction of expression of transforming growth factor-beta1 and its receptor type II. J Neuroimmunol 1998; 91: 73–81.

35. Stuve O, Chabot S, Jung SS, Williams G, Yong VW. Chemokine-enhanced migration of human peripheral blood mononuclear cells is antagonized by interferon beta-1b through an effect on matrix metalloproteinase-9. J Neuroimmunol 1997; 80: 38–46.

36. Pilling D, Akbar AN, Girdlestone J, et al. Interferon-beta mediates stromal cell rescue of T cells from apoptosis. Eur J Immunol 1999; 29: 1041–1050.

37. Nagaraju K, Raben N, Loeffler L, et al. Conditional up-regulation of MHC class I in skeletal muscle leads to self-sustaining autoimmune myositis and myositis-specific autoantibodies. Proc Natl Acad Sci U S A. 2000; 97(16): 9209–14.

38. Confalonieri P, Bernasconi P, Cornelio F, Mantegaya R. Transforming growth factor-beta 1 in polymyositis and dermatomyositis correlates with fibrosis but not with mononuclear cell infiltrate. J Neuropathol Exp Neurol 1997; 56: 479–84.

39. Amemiya K, Semino-Mora C, Granger RP, Dalakas MC. Downregulation of TGF-beta1 mRNA and protein in the muscles of patients with inflammatory myopathies after treatment with high-dose intravenous immunoglobulin. Clin Immunol 2000; 94: 99–104.

40. Tawil R, Griggs R, Jackson C, et al. Randomized pilot trial of beta IFN1a (Avonex) in patients with inclusion body myositis. Neurology 2001; 57: 1566–1570.

41. Iguchi H, Kishi M, Fujioka T, Wakata N, Kinoshita M. Polymyositis after interferon beta treatment of chronic hepatitis type C. Rinsho Shinkeigaku 1996; 36: 22–4.

42. Lunemann JD, Kassim N, Zschenderlein R, Zipp F, Schwarzenberger B. Rhabdomyolysis during interferon-beta 1a treatment. J Neurol Neurosurg Psychiatry 2002; 72: 274.

43. Iarlori C, Reale M, Lugaresi A, et al. RANTES production and expression is reduced in relapsing-remitting multiple sclerosis patients treated with interferon-beta-1b. J Neuroimmunol 2000; 107: 100–7.

44. Isenberg, D.A, Allen E, Farewell V, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 2004; 41: 49–54.

45. Rider LG, Giannini EH, Brunner HI, et al. International consensus on preliminary definitions of improvement in adult and juvenile myositis. Arthritis Rheum 2004; 50: 2281–90.

46. Hoogendijk JE, Amato AA, Lecky BR, 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.

47. Fleckenstein JL. Re: Cost-effectivness of MR imaging in evaluating polymyositis. AJR 1996; 167: 531–2.

48. Studynkova JT, Kuchen S, Jeisy E, et al. The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis. Clin Exp Rheumatol. 2004; 22(4): 395–402.

49. Lampa J, Nennesmo I, Einarsdottir H, Lundberg I. MRI guided muscle biopsy confirmed polymyositis diagnosis in a patient with interstitial lung disease. Ann Rheum Dis 2001; 60(4): 423–6.

50. Adams EM, Chow CK, Premkumar A, Plotz PH. The idiopathic inflammatory myopathies: spectrum of MR imaging findings. Radiographics 1995; 15(3): 563–74.

51. Yosipovitch G, Beniaminov O, Rousso I, David M. STIR magnetic resonance imaging: a noninvasive method for detection and follow-up of dermatomyositis. Arch Dermatol 1999; 135(6): 721–3.

52. Oddis CV. Idiopathic inflammatory myopathies: a treatment update. Curr Rheumatol Rep 2003; 5: 431–6.

53. Villaba L, Hicks JE, Adams EM, Sherman JB, Gourley MF, Leff RL, et al. Treatment of refractory myositis. Arthritis Rheum 1998; 41: 392–9.

54. Riley P, Maillard SM, Wedderburn LR, Woo P, Murray KJ, Pilkington CA. Intravenous cyclophosphamide pulse therapy in juvenile dermatomyositis. A review of efficacy and safety. Rheumatology (Oxford) 2004; 43: 491–6.

55. Chaudhry V, Cornblath DR, Griffin JW, O’Brien R, Drachman DB. Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases. Neurology 2001; 56: 94–6.

56. Tausche A-K, Meurer M. Mycophenolate mofetil for dermatomyositis. Dermatology 2001; 202: 341–3.

57. Labioche I, Liozon E, Weschler B, Loustaud-Ratti V, Soria P, Vidal E. Refractory polymyositis responding to infliximab: extended follow-up. Rheumatology 2004; 43: 531–2.

58. Musial J, Undas A, Celinska-Lowenhoff M. Polymyositis associated with infliximab treatment for rheumatoid arthritis. Rheumatology 2003; 42: 1566–8.

59. Sprott H, Glatzel M, Michel BA. Treatment of myositis with etanercept (Enbrel), a recombinant human soluble fusion protein of TNF-alpha type II receptor and IgG1. Rheumatology 2004; 43: 524–6.

60. Takada K, Bookbinder S, Furie R, et al. A pilot study of eculizumab in patients with dermatomyositis. Arthritis Rheum 2002; 46(Suppl): S489 (abstrakt 1300).

61. Levine TD. A pilot study of rituximab therapy for refractory dermatomyositis. Arthritis Rheum 2002; 46(Suppl): S488 (abstrakt 1299).

62. Bingham S, Griffiths B, McGonagle D, Snowden JA, Morgan G, Emery P. Autologous stem cell transplantation for rapidly progressive Jo-1 positive polymyositis with long-term follow-up. Br J Haematol 2001; 113: 840–1.

63. Tomasová Studýnková J, Kuchen S, Jeisy E, Schedel J, Charvát F, Jarošová K, Sprott H, Matucci-64. Cerinic M, Gay RE,. Michel BA, Pavelka K, Vencovský J, Gay S. The expression of cyclooxygenase–1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis. Clin Exp Rheumatol 2004; 22(4): 395–402.

64. Tomasová Studýnková J, Niederlová J, Jarošová K, Charvát F, Lacman J, Cimburek Z, Vencovský J. Imunohistologická analýza svalů nemocných s polymyozitidou a dermatomyozitidou. Exprese chemokinů, jejich receptorů a cytokinů v postižených a nepostižených svalech rozeznávaných pomocí magnetické rezonance. Rheumatologia 2002; 3: 107–16.

65. Tomasová Studýnková J, Charvát F, Jarošová K, Vencovský J. The role of MRI investigation in the assessment of polymyositis and dermatomyositis. Rheumatology (Oxford). V tisku.

66. Vencovský J, Jarošová K, Macháček S, Studýnková J, Kafková J, Bartůňková J, Němcová D, Charvát F. Cyclosporin A versus methotrexate in the treatment of polymyositis and dermatomyositis. Scand J Rheumatol 2000; 29: 95–10.

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