Mixed connective tissue disease: what is behind the curtain?

Best Practice and Research: Clinical Rheumatology

Volumn 21, Issue 6, 2007, Pages 1037-1049

  Aringer, Martin ^a   Smolen, Josef S ^b  

^a Division of Rheumatology   (Germany)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

anti RNP antibodies; erosive arthritis; mixed connective tissue disease; myositis; overlap syndromes; Raynaud's

Indexed keywords

AUTOANTIBODY; AZATHIOPRINE; BOSENTAN; CALCIUM CHANNEL BLOCKING AGENT; CENTROMERE ANTIBODY; CHLOROQUINE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DNA TOPOISOMERASE; HYDROXYCHLOROQUINE; IMMUNOGLOBULIN; METHOTREXATE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PHOSPHODIESTERASE INHIBITOR; PREDNISONE; PROSTACYCLIN; PROSTAGLANDIN; RIBONUCLEOPROTEIN ANTIBODY; SILDENAFIL; SM ANTIBODY; SYNTHETASE; UNIPROST;

ANTIBODY TITER; ARTHRITIS; COMORBIDITY; DISEASE MODEL; DISEASE SEVERITY; ECHOCARDIOGRAPHY; GENETIC ASSOCIATION; HUMAN; MIXED CONNECTIVE TISSUE DISEASE; MYOSITIS; PATHOPHYSIOLOGY; PATIENT MONITORING; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RAYNAUD PHENOMENON; REVIEW; SEROLOGY; SYSTEMIC SCLEROSIS;

AUTOIMMUNITY; DIAGNOSIS, DIFFERENTIAL; HUMANS; IMMUNITY, CELLULAR; MIXED CONNECTIVE TISSUE DISEASE;

EID: 36649010610     PISSN: 15216942     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.berh.2007.10.002     Document Type: Review

References (80)

1. Sharp G.C., Irvin W.S., Tan E.M., et al. Mixed connective tissue disease - an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). American Journal of Medicine 52 (1972) 148-159
2. Sharp G.C., Irvin W.S., May C.M., et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. The New England Journal of Medicine 295 (1976) 1149-1154
3. Black C., and Isenberg D.A. Mixed connective tissue disease - goodbye to all that. British Journal of Rheumatology 31 (1992) 695-700
4. Alarcon-Segovia D. Shared autoimmunity: a concept for which the time has come. Autoimmunity 38 (2005) 201-203
5. Schellekens G.A., de Jong B.A., van den Hoogen F.H., et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. The Journal of Clinical Investigation 101 (1998) 273-281
6. Targoff I.N. Autoantibodies in polymyositis. Rheumatic Disease Clinics of North America 18 (1992) 455-482
7. Marguerie C., Bunn C.C., Beynon H.L., et al. Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. The Quarterly Journal of Medicine 77 (1990) 1019-1038
8. Hengstman G.J., van Engelen B.G., Vree Egberts W.T., and van Venrooij W.J. Myositis-specific autoantibodies: overview and recent developments. Current Opinion In Rheumatology 13 (2001) 476-482
9. Walker U.A., Tyndall A., Czirjak L., et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database. Annals of the Rheumatic Diseases 66 (2007) 754-763
10. Reimer G., Steen V.D., Penning C.A., et al. Correlates between autoantibodies to nucleolar antigens and clinical features in patients with systemic sclerosis (scleroderma). Arthritis & Rheumatism 31 (1988) 525-532
11. Steen V.D. Autoantibodies in systemic sclerosis. Seminars in Arthritis and Rheumatism 35 (2005) 35-42
12. Sgonc R., Gruschwitz M.S., Dietrich H., et al. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. The Journal of Clinical Investigation 98 (1996) 785-792
13. Baroni S.S., Santillo M., Bevilacqua F., et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. The New England Journal of Medicine 354 (2006) 2667-2676
14. Servettaz A., Tamby M.C., Guilpain P., et al. Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B). Clinical Immunology 120 (2006) 212-219
15. Hu P.Q., Fertig N., Medsger Jr. T.A., and Wright T.M. Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis & Rheumatism 48 (2003) 1363-1373
16. Henault J., Robitaille G., Senecal J.L., and Raymond Y. DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti-topoisomerase I autoantibodies from systemic sclerosis patients. Arthritis & Rheumatism 54 (2006) 963-973
17. Henault J., Tremblay M., Clement I., et al. Direct binding of anti-DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis. Arthritis & Rheumatism 50 (2004) 3265-3274
18. Williams H.J., Alarcon G.S., Joks R., et al. Early undifferentiated connective tissue disease (CTD). VI. An inception cohort after 10 years: disease remissions and changes in diagnoses in well established and undifferentiated CTD. The Journal of Rheumatology 26 (1999) 816-825
19. Bodolay E., Csiki Z., Szekanecz Z., et al. Five-year follow-up of 665 Hungarian patients with undifferentiated connective tissue disease (UCTD). Clinical and Experimental Rheumatology 21 (2003) 313-320
20. Mosca M., Neri R., Bencivelli W., et al. Undifferentiated connective tissue disease: analysis of 83 patients with a minimum follow up of 5 years. The Journal of Rheumatology 29 (2002) 2345-2349
21. Swaak A.J., van de B.H., Smeenk R.J., et al. Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT). Rheumatology (Oxford) 40 (2001) 89-94
22. Grennan D.M., Bunn C., Hughes G.R., et al. Frequency and clinical significance of antibodies to ribonucleoprotein in SLE and other connective tissue disease subgroups. Annals of the Rheumatic Diseases 36 (1977) 442-447
23. Habets W.J., de Rooij D.J., Hoet M.H., et al. Quantitation of anti-RNP and anti-Sm antibodies in MCTD and SLE patients by immunoblotting. Clinical and Experimental Immunology 59 (1985) 457-466
24. Vlachoyiannopoulos P.G., Guialis A., Tzioufas G., and Moutsopoulos H.M. Predominance of IgM anti-U1RNP antibodies in patients with systemic lupus erythematosus. British Journal of Rheumatology 35 (1996) 534-541
25. Frandsen P.B., Kriegbaum N.J., Ullman S., et al. Follow-up of 151 patients with high-titer U1RNP antibodies. Clinical Rheumatology 15 (1996) 254-260
26. Lerner M.R., and Steitz J.A. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proceedings of the National Academy of Sciences of the United States of America 76 (1979) 5495-5499
27. Lundberg I., Nyman U., Pettersson I., and Hedfors E. Clinical manifestations and anti-(U1)snRNP antibodies: a prospective study of 29 anti-RNP antibody positive patients. British Journal of Rheumatology 31 (1992) 811-817
28. Hof D., Cheung K., de Rooij D.J., et al. Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease. Arthritis Research & Therapy 7 (2005) R302-R309
29. Greidinger E.L., Foecking M.F., Ranatunga S., and Hoffman R.W. Apoptotic U1-70 kd is antigenically distinct from the intact form of the U1-70-kd molecule. Arthritis & Rheumatism 46 (2002) 1264-1269
30. Okawa-Takatsuji M., Aotsuka S., Uwatoko S., et al. Endothelial cell-binding activity of anti-U1-ribonucleoprotein antibodies in patients with connective tissue diseases. Clinical and Experimental Immunology 126 (2001) 345-354
31. Okawa-Takatsuji M., Aotsuka S., Uwatoko S., et al. Increase of cytokine production by pulmonary artery endothelial cells induced by supernatants from monocytes stimulated with autoantibodies against U1-ribonucleoprotein. Clinical and Experimental Rheumatology 17 (1999) 705-712
32. Furtado R.N., Pucinelli M.L., Cristo V.V., et al. Scleroderma-like nailfold capillaroscopic abnormalities are associated with anti-U1-RNP antibodies and Raynaud's phenomenon in SLE patients. Lupus 11 (2002) 35-41
33. Reichlin M., and van Venrooij W.J. Autoantibodies to the URNP particles: relationship to clinical diagnosis and nephritis. Clinical and Experimental Immunology 83 (1991) 286-290
34. Greidinger E.L., Zang Y., Jaimes K., et al. A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen. Arthritis & Rheumatism 54 (2006) 661-669
35. Burdt M.A., Hoffman R.W., Deutscher S.L., et al. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis & Rheumatism 42 (1999) 899-909
36. Bodolay E., Szekanecz Z., Devenyi K., et al. Evaluation of interstitial lung disease in mixed connective tissue disease (MCTD). Rheumatology (Oxford) 44 (2005) 656-661
37. Leibfarth J.H., and Persellin R.H. Characteristics of patients with serum antibodies to extractable nuclear antigens. Arthritis & Rheumatism 19 (1976) 851-856
38. Cohen M.L., Dawkins B., Dawkins R.L., and Owen E.T. Clinical significance of antibodies to ribonucleoprotein. Annals of the Rheumatic Diseases 38 (1979) 74-78
39. Smolen J.S., and Steiner G. Mixed connective tissue disease: to be or not to be?. Arthritis & Rheumatism 41 (1998) 768-777
40. Farber S.J., and Bole G.G. Antibodies to components of extractable nuclear antigen. Clinical characteristics of patients. Archives of Internal Medicine 136 (1976) 425-431
41. van den Hoogen F.H., Spronk P.E., Boerbooms A.M., et al. Long-term follow-up of 46 patients with anti-(U1)snRNP antibodies. British Journal of Rheumatology 33 (1994) 1117-1120
42. Prakash U.B. Lungs in mixed connective tissue disease. Journal of Thoracic Imaging 7 (1992) 55-61
43. Ramos-Niembro F., Alarcon-Segovia D., and Hernandez-Ortiz J. Articular manifestations of mixed connective tissue disease. Arthritis & Rheumatism 22 (1979) 43-51
44. Piirainen H.I. Patients with arthritis and anti-U1-RNP antibodies: a 10-year follow-up. British Journal of Rheumatology 29 (1990) 345-348
45. O'Connell D.J., and Bennett R.M. Mixed connective tissue disease - clinical and radiological aspects of 20 cases. British Journal of Radiology 50 (1977) 620-625
46. Takasaki Y., Yamanaka K., Takasaki C., et al. Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease. Modern Rheumatology 14 (2004) 367-375
47. Gendi N.S., Welsh K.I., van Venrooij W.J., et al. HLA type as a predictor of mixed connective tissue disease differentiation. Ten-year clinical and immunogenetic followup of 46 patients. Arthritis & Rheumatism 38 (1995) 259-266
48. Berglin E., Padyukov L., Sundin U., et al. A combination of autoantibodies to cyclic citrullinated peptide (CCP) and HLA-DRB1 locus antigens is strongly associated with future onset of rheumatoid arthritis. Arthritis Research & Therapy 6 (2004) R303-R308
49. Oxenhandler R., Hart M., Corman L., et al. Pathology of skeletal muscle in mixed connective tissue disease. Arthritis & Rheumatism 20 (1977) 985-988
50. Bennett R.M., and O'Connell D.J. Mixed connective tisssue disease: a clinicopathologic study of 20 cases. Seminars in Arthritis and Rheumatism 10 (1980) 25-51
51. Hall S., and Hanrahan P. Muscle involvement in mixed connective tissue disease. Rheumatic Disease of Clinics North America 31 (2005) 509-517 vii
52. Barakat S., Briand J.P., Abuaf N., et al. Mapping of epitopes on U1 snRNP polypeptide A with synthetic peptides and autoimmune sera. Clinical and Experimental Immunology 86 (1991) 71-78
53. Skriner K., Sommergruber W.H., Tremmel V., et al. Anti-A2/RA33 autoantibodies are directed to the RNA binding region of the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. Differential epitope recognition in rheumatoid arthritis, systemic lupus erythematosus, and mixed connective tissue disease. The Journal of Clinical Investigation 100 (1997) 127-135
54. Hassan A.B., Nikitina-Zake L., Padyukov L., et al. MICA4/HLA-DRB1*04/TNF1 haplotype is associated with mixed connective tissue disease in Swedish patients. Human Immunology 64 (2003) 290-296
55. Hoffman R.W., Rettenmaier L.J., Takeda Y., et al. Human autoantibodies against the 70-kd polypeptide of U1 small nuclear RNP are associated with HLA-DR4 among connective tissue disease patients. Arthritis & Rheumatism 33 (1990) 666-673
56. Hameenkorpi R., Ruuska P., Forsberg S., et al. More evidence of distinctive features of mixed connective tissue disease. Scandinavian Journal of Rheumatology 22 (1993) 63-68
57. Dong R.P., Kimura A., Hashimoto H., et al. Difference in HLA-linked genetic background between mixed connective tissue disease and systemic lupus erythematosus. Tissue Antigens 41 (1993) 20-25
58. Ruuska P., Hameenkorpi R., Forsberg S., et al. Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus. Annals of the Rheumatic Diseases 51 (1992) 52-55
59. Kaneoka H., Hsu K.C., Takeda Y., et al. Molecular genetic analysis of HLA-DR and HLA-DQ genes among anti-U1-70-kd autoantibody positive connective tissue disease patients. Arthritis & Rheumatism 35 (1992) 83-94
60. Black C.M., Maddison P.J., Welsh K.I., et al. HLA and immunoglobulin allotypes in mixed connective tissue disease. Arthritis & Rheumatism 31 (1988) 131-134
61. Genth E., Zarnowski H., Mierau R., et al. HLA-DR4 and Gm(1,3;5,21) are associated with U1-nRNP antibody positive connective tissue disease. Annals of the Rheumatic Diseases 46 (1987) 189-196
62. Amigues J.M., Cantagrel A., Abbal M., and Mazieres B. Comparative study of 4 diagnosis criteria sets for mixed connective tissue disease in patients with anti-RNP antibodies. Autoimmunity Group of the Hospitals of Toulouse. The Journal of Rheumatology 23 (1996) 2055-2062
63. Alarcon-Segovia D., and Villareal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R., and Sharp G.C. (Eds). Mixed connective tissue diseases and antinuclear antibodies (1987), Elsevier, Amsterdam 41-47
64. Aringer M., Steiner G., and Smolen J.S. Does mixed connective tissue disease exist? Yes. Rheumatic Disease Clinics of North America 31 (2005) 411-420
65. Grader-Beck T., and Wigley F.M. Raynaud's phenomenon in mixed connective tissue disease. Rheumatic Disease of Clinics North America 31 (2005) 465-481 vi
66. Pope J.E. Other manifestations of mixed connective tissue disease. Rheumatic Disease Clinics of North America 31 (2005) 519-533 vii
67. Bull T.M., Fagan K.A., and Badesch D.B. Pulmonary vascular manifestations of mixed connective tissue disease. Rheumatic Disease Clinics of North America 31 (2005) 451-464 vi
68. Gluck T., Muller-Ladner U., Speicher A., et al. Fatal sinus vein thrombosis in a patient with mixed connective tissue disease and secondary antiphospholipid antibody syndrome. Medizinische Klinik (Munich) 96 (2001) 361-364
69. Mendonca L.L., Amengual O., Atsumi T., et al. Most anticardiolipin antibodies in mixed connective tissue disease are beta2-glycoprotein independent. The Journal of Rheumatology 25 (1998) 189-190
70. Venables P.J. Mixed connective tissue disease. Lupus 15 (2006) 132-137
71. Kitridou R.C., Akmal M., Turkel S.B., et al. Renal involvement in mixed connective tissue disease: a longitudinal clinicopathologic study. Seminars in Arthritis and Rheumatism 16 (1986) 135-145
72. Kim P., and Grossman J.M. Treatment of mixed connective tissue disease. Rheumatic Disease Clinics of North America 31 (2005) 549-565 viii
73. Greenberg S.A., and Amato A.A. Inflammatory myopathy associated with mixed connective tissue disease and scleroderma renal crisis. Muscle & Nerve 24 (2001) 1562-1566
74. Sullivan W.D., Hurst D.J., Harmon C.E., et al. A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine (Baltimore) 63 (1984) 92-107
75. Hammann C., Genton C.Y., Delabays A., et al. Myocarditis of mixed connective tissue disease: favourable outcome after intravenous pulsed cyclophosphamide. Clinical Rheumatology 18 (1999) 85-87
76. Bhinder S., Harbour K., and Majithia V. Transverse myelitis, a rare neurological manifestation of mixed connective tissue disease - a case report and a review of literature. Clinical Rheumatology 26 (2007) 445-447
77. Ulmer A., Kotter I., Pfaff A., and Fierlbeck G. Efficacy of pulsed intravenous immunoglobulin therapy in mixed connective tissue disease. Journal of American Academy of Dermatology 46 (2002) 123-127
78. Matsuda M., Miki J., Oguchi K., et al. Fasciitis in mixed connective tissue disease successfully treated with high-dose intravenous immunoglobulin. Internal Medicine 42 (2003) 910-911
79. Christopher-Stine L., and Wigley F. Tumor necrosis factor-alpha antagonists induce lupus-like syndrome in patients with scleroderma overlap/mixed connective tissue disease. The Journal of Rheumatology 30 (2003) 2725-2727
80. Cohen L.E., Faske I., Fenske N.A., and Greist M.A. Prostaglandin infusion therapy for intermittent digital ischemia in a patient with mixed connective tissue disease. Case report and review of the literature. Journal of American Academy of Dermatology 20 (1989) 893-897