Skip to main content
SpringerLink
Log in

Clinical profiles of patients with antibodies to nuclear ribonucleoprotein

  • Originals
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Summary

Currently there are no widely accepted criteria for the diagnosis of MCTD. In this work we attempted to define the clinical profile of a group of 68 patients with anti nRNP antibodies, detected by immunoprecipitation in 0.6% agarose. The diagnosis of each collagen vascular disease was established in every patient, who met with the strict diagnostic criteria either at clinical presentation or during the follow-up period. Twenty-eight patients had SLE, 9 had classical erosive RA, three had PSS and one had PM. The only distinctive features in the group of SLE with anti nRNP was an increased incidence of anti Sm antibodies (p<0.05). In the RA group there was a trend towards a high frequency of Raynaud's phenomenon and swollen hands. At clinical presentation twenty-seven patients did not fulfil enough criteria to be diagnosed of any of the well-defined collagen vascular disease. They presented an undifferentiated syndrome, characterized clinically by Raynaud's phenomenon (100%), swollen hands (88.9%) and joint symptoms (88.9%), with scarce tendency of developing severe systemic manifestations. The main laboratory abnormalities in this group were hipergammaglobulinemia, mildly increased ESR, abnormal levels of CIC, negative anti nDNA and anti Sm antibodies, and the virtual absence of hipocomplementemia. During a clinical course of 96±72.5 months only one patient evolved into another collagen disease (SLE). The clinical course in the remaining cases, was stable improving with low doses of prednisone and/or NSAID. We suggest considering this undifferentiated syndrome as a distinct entity, for which the already classical term of MCTD could be reserved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Keil, H., Dermatomyositis and systemic lupus erythematosus. A clinical report of transitional cases with consideration of lead as a possible etiologic factor. Arch Int Med., 1940, 60, 109–139.

    Google Scholar 

  2. Rowell, N.R. Lupus erythematosus cells in systemic sclerosis. Ann Rheum Dis, 1962, 21, 70–75.

    Article  PubMed  CAS  Google Scholar 

  3. Tuffanelli, D.L., Winkelman, R.K. Systemic sclerodermia: A clinical study of 727 cases. Arch Dermatol, 1961, 84, 359–371.

    PubMed  CAS  Google Scholar 

  4. Estes, D., Christian, C.L. The natural history of systemic lupus erythematosus by prospective analysis. Medicine (Baltimore), 1971, 50, 85–95.

    CAS  Google Scholar 

  5. Sharp, G.C., Irwin, W.S., Tan, E.M., Gould, R.G., Holman, H.R. Mixed connective tissue disease. An apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Amer J Med, 1972, 52, 145–159.

    Google Scholar 

  6. Mattioli, M., Reichlin, M. Characterization of a soluble nuclear ribonucleoprotein antigen reactive with SLE sera. J Immunol, 1971, 197, 1281–1290.

    Google Scholar 

  7. Tan, E.M., Kunkel, H.G. Characteristics of a soluble nuclear antigen, precipitating with sera of patients with systemic lupus erythematosus. J Immunol, 1966, 96, 464–471.

    PubMed  CAS  Google Scholar 

  8. Sharp, G.C., Irwin, W.S., May, C.M., Holman, H.R., McDuffie, F.C., Hess, E.V., Schmid, F.R. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective tissue disease, systemic lupus erythematosus and other rheumatic diseases. N EngI J Med, 1976, 295, 1149–1154.

    Article  CAS  Google Scholar 

  9. Bresnihan, B., Bunn, C., Snaith, M.L., Hughes, G.R. Antiribonucleoprotein antibodies in connective tissue diseases: estimation by counterimmunoelectrophoresis. Br Med J, 1977, 1, 610–611.

    Article  PubMed  CAS  Google Scholar 

  10. O'Connell, D.J., Bennett, R.M. Mixed connective tissue disease — clinical and radiological aspects of 20 cases. Br J Radiol, 50, 1977, 620–625.

    Article  PubMed  Google Scholar 

  11. Parker, M.D. Ribonucleoprotein antibodies: frequency and clinical significance in systemic lupus erythematosus, scleroderma and connective tissue disease. J Lab Clin Md, 1973, 82, 769–775.

    CAS  Google Scholar 

  12. Ramos-Niembro, F., Alarcon-Segovia, D., Hernandez-Ortiz, J. Articular manifestations of mixed connective tissue disease. Arthritis Rheum, 1979, 22, 43–51.

    Article  PubMed  CAS  Google Scholar 

  13. Farber, S.J., Bole, G.C. Antibodies to components of extractable nuclear antigen. Clinical characteristics of patients. Arch Int Med, 1976, 136, 425–431.

    Article  CAS  Google Scholar 

  14. Leibfarth, J.H., Persellin, R.H. Characteristics of patients with serum antibodies to extractable nuclear antigens. Arthritis Rheum, 1976, 19, 851–856.

    Article  PubMed  CAS  Google Scholar 

  15. Hamburger, M., Hodes, S., Borland, P. The incidence and clinical significance of antibodies to ENA. Am J Med Sci, 1977, 273, 21–28.

    Article  PubMed  CAS  Google Scholar 

  16. Maddison, P.J., Mogavero, H., Reichlin, M. Patterns of clinical disease associated with antibodies to nuclear ribonucleoprotein. J Rheumatol, 1978, 5, 407–411.

    PubMed  CAS  Google Scholar 

  17. Le Roy, E.C., Maricq, H.R, Kahalen, M. Undifferentiated connective tissue syndromes. Arthritis Rheum, 1980, 23, 341–343.

    Article  PubMed  Google Scholar 

  18. McCain, G.A., Bell, D.A., Ghodirker, W.B., Komar, R.R. Antibody to extractable nuclear antigen in the rheumatic diseases. J Rheumatol, 1978, 5, 399–406.

    PubMed  CAS  Google Scholar 

  19. Grant, K.D., Adams, L.E., Hess, E.V. Mixed connective tissue disease — a subset with sequential clinical and laboratory features. J Rheumatol, 1981, 8, 587–598.

    PubMed  CAS  Google Scholar 

  20. Weiss, T.D., Nelson, J.S., Woolsey, R.M., Zuckner, J., Baldasare, A. Transverse myelitis in mixed connective tissue disease. Arthritis Rheum, 1978, 21, 982–986.

    Article  PubMed  CAS  Google Scholar 

  21. Sharp, G.C. Mixed connective tissue disease. Bull Rheum Dis, 1975, 25, 828–831.

    CAS  Google Scholar 

  22. Bennett, R.M., Bong, D.M., Spargo, B.H. Neuropsychiatric problems in mixed connective tissue disease. Am J Med, 1978, 65, 955–962.

    Article  PubMed  CAS  Google Scholar 

  23. Fuller, T.J., Richamn, A.V., Auerbach, D., Alexander, R.W., Lottenberg, R., Longley, S. Immunecomplex glomerulonephritis in a patient with mixed connective tissue disease. Am J Med, 1977, 62, 761–764.

    Article  PubMed  CAS  Google Scholar 

  24. Wolfe, J.E., Kingsland, L., Lindberg, D., Sharp, G.C. Disease pattern in patients with antibodies only to nuclear ribonucleoprotein. Clin Res, 1977, 25, 438A.

    Google Scholar 

  25. Rao, K.V., Berksth, R.D., Grosson, J.T. Immunecomplex nephritis in mixed connective tissue disease (letter). Ann Int Med, 1976, 84, 174.

    PubMed  CAS  Google Scholar 

  26. Singsen, B.H., Landing, B., Wolfe, J.F., Bernstein, B., Oxenhandler, R.W., Sharp, G.C., Hanson, V. Histologic evaluation of mixed connective tissue disease in children and in adults (Abstract). Arthritis Rheum, 1978, 21, 593.

    Article  Google Scholar 

  27. Parker, C., Levitt, R., Uitto, J., Bruce, R., Roberts R., Kissane, J. Mixed connective tissue disease. Am J Med, 1978, 65, 833–842.

    Article  PubMed  Google Scholar 

  28. Harmon, C., Wolfe, J.F., Lillard, S., Held, C., Cordon, R., Sharp, G.C. Pulmonary involvement in mixed connective tissue disease (MCTD) (Abstract). Arthritis Rheum, 1976, 19, 801.

    Google Scholar 

  29. Jones, M.B., Osterholm, R.K., Wilson, R.B., Martin, F.H., Commers, J.R., Bachmayer, J.D. Fatal pulmonary hypertension and resolving immune complex glomerulonephritis in mixed connective tissue disease. A case report and review of the literature. Am J Med, 1978, 65, 855–863.

    Article  PubMed  CAS  Google Scholar 

  30. Rosenberg, A.M., Petty, R.E., Cumming, G.R., Koehler, B.E. Pulmonary hypertension in a child with MCTD. J Rheumatol, 1979, 6, 700–704.

    PubMed  CAS  Google Scholar 

  31. Wiener-Kronish, J.P., Solinger, A.M., Warnock, M.L., Churg, A., Ordonez, N., Golden, J. Severe pulmonary involvement in mixed connective tissue disease. Am Rev Resp Dis, 1981, 124, 499–503.

    PubMed  CAS  Google Scholar 

  32. Norman, D.A., Fleischmann, R.M. Gastrointestinal systemic sclerosis in serologic mixed connective tissue disease. Arthritis Rheum, 1978, 21, 811–819.

    Article  PubMed  CAS  Google Scholar 

  33. Halla, J.T., Hardin, J.G. Clinical features of the arthritis of mixed connective tissue disease. Arthritis Rheum, 1978, 21, 497–503.

    Article  PubMed  CAS  Google Scholar 

  34. Lacombe, P., Zenny, J.C., Benhamou, L., Chevrot, A., Pallardy, G. Signes radiologiques des connectivites mixtes avec anticorps anti-RNP. A propos de 20 observations. J Radiol, 1981, 62, 417–423.

    PubMed  CAS  Google Scholar 

  35. Udoff, E.J., Genant, H.K., Kozin, F., Ginsberg, M. Mixed connective tissue disease: The spectrum of radiologic manifestations. Radiology, 1977, 125, 613–618.

    PubMed  Google Scholar 

  36. Gilliam, J.N., Pristowsky, S.D. Conversion of discoid lupus erythematosus to mixed connective tissue disease. J Rheumatol, 1977, 4, 165–169.

    PubMed  CAS  Google Scholar 

  37. Gilliam, J.N, Pristowsky, S.D. Mixed connective tissue disease syndrome: cutaneous manifestations of patients with epidermal nuclear staining and high titer serum antibody to ribonuclease-sensitive extractable nuclear antigen. Arch Dermatol, 1977, 113, 583–587.

    Article  PubMed  CAS  Google Scholar 

  38. Bennet, R.M., O'Connel, D.J. Mixed connective tissue disease. A clinico-pathologic study of 20 cases. Semin Arthritis Rheum, 1980, 10, 25–51.

    Article  PubMed  Google Scholar 

  39. Johansson, E.A., Niemi, K.M., Lassus, A., Gripenberg, M. Mixed connective tissue disease: A follow-up study of 12 patients with special reference to cold sensitivity and skin manifestations. Acta Derm Venerol (Stockh), 1981, 61, 225–231.

    CAS  Google Scholar 

  40. Cook, C.L., Lurie, H.I. Fatal gastrointestinal hemorrhage in mixed connective tissue disease. Arthritis Rheum, 1977, 20, 1421–1427.

    Article  PubMed  Google Scholar 

  41. Sharp, G.C., Anderson, P.C. Current concepts in the classification of connective tissue disease. J Am Acad Dermatol, 1980, 2, 269–279.

    Article  PubMed  CAS  Google Scholar 

  42. Nimelstein, S.H., Brody, S., McShane, D., Holman, H.R. Mixed connective tissue disease: A subsequent evaluation of the original 25 patients. Medicine (Baltimore), 1980, 59, 239–248.

    CAS  Google Scholar 

  43. Ropes, M.W., Bennett, E.A., Cobb, S., Jacox, R., Jessar, R. Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis, 1958, 9, 175–176.

    PubMed  CAS  Google Scholar 

  44. Subcommitte for Scleroderma Criteria of the American Rheumatism Association. Diagnostic and therapeutic criteria for classification of systemic sclerosis (scleroderma). Arthritis Rheum, 1980, 23, 581–590.

    Article  Google Scholar 

  45. Cohen, A.S., Reynolds, W.E., Franklin, E.C., Kulka, J.P., Ropes, M.W., Shulman, L.E., Wallace, S.L. Preliminary criteria for the classification of systemic lupus erythematosus. Bull Rheum Dis, 1971, 21, 643–648.

    Google Scholar 

  46. Bohan, A., Peter, J.B., Bowman, R.L., Pearson, C.M. A computer-assisted analysis on 153 patients with polymyositis and dermatomyositis. Medicine (Baltimore), 1977, 56, 255–286.

    CAS  Google Scholar 

  47. Northway, J.D., Tan, E.M. Differentiation of antinuclear antibodies giving speckled patterns in immunofluorescence. Clin Immunol Immunopathol, 1972, 1, 140–144.

    Article  CAS  Google Scholar 

  48. Theophilopoulos, A.N., Wilson, C.B., Dixon, F.J. The Raji cell radioimmuno assay for detecting immune complexes in human sera. J Clin Invest, 1976, 57, 169–182.

    Article  PubMed  Google Scholar 

  49. Hay, F.C., Nineham, L.J., Roitt, M. Routine assay for detection of immune complexes of known immunoglobulin class using solid phase Clq. Clin Exp Immuol, 1976, 24, 396–400.

    CAS  Google Scholar 

  50. Langone, J.A., Boyle, M.D.P., Borsos, T.125I — Protein A: Application to the quantitative determination of fluid phase and cell-bound IgG. J Immunol Methods, 1977, 18, 281–293.

    Article  PubMed  CAS  Google Scholar 

  51. Aarden, L.A., Lakmaker, F., De Groot, E.R., Feltkamp, T.E.W. Immunology of DNA. III Crithidia Luciliae. A simple substrate for the determination of anti Ds DNA with the immunofluorescence technique. Ann Y Acad Sci, 1975, 254, 505–514.

    Article  CAS  Google Scholar 

  52. Chubick, A., Southeimer, R.D., Gilliam, J.N., Ziff, M. An appraisal of tests for native DNA antibodies in connective tissue disease. Ann Int Med, 1978, 89, 186–192.

    PubMed  CAS  Google Scholar 

  53. Weisman, M., Zvaifler, N. Cryoimmunoglubulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis. J Clin Invest, 1975, 56, 725–739.

    Article  PubMed  CAS  Google Scholar 

  54. Keiser, H.D., Weinstein, J. The detection and identification of antibodies to salin extractable nuclear antigens by counterimmuno electrophoreses. Arthritis Rheum, 1980, 23, 1026–1035.

    Article  PubMed  CAS  Google Scholar 

  55. Grennan, D.M., Bunn, C., Hughes, G.R.V., Buchanan, W.W., Dick, W.C. Frequency and clinical significance of antibodies to ribonucleoprotein in SLE and other connective tissue disease subgroups. Ann Rheum Dis, 1977, 36, 442–447.

    Article  PubMed  CAS  Google Scholar 

  56. Hamburger, M., Fiedlander, L., Borland, P. Interactions of extractable nuclear (ENA) and doublestranded DNA. Arthritis Rheum, 1974, 17, 469–475.

    Article  PubMed  CAS  Google Scholar 

  57. Gaudreau, A., Amor, B., Kahn, M.F., Ryckewaert, A., Sany, J., Peltier, A.P. Clinical significance of antibodies to ENA. Ann Rheum Dis, 1978, 37, 321–327.

    Article  PubMed  CAS  Google Scholar 

  58. Reichlin, M., Mattioli, M. Correlation of a precipitin reaction to an RNA protein antigen and a low prevalence of nephritis in patients with systemic lupus erythematosus. N Engl J Med, 1972, 286, 208–211.

    Article  Google Scholar 

  59. Anderson, C.L., Stillman, W.S. Raji cell assay for immune complexes: evidence for detection of Rajidirected immunoglobulin G antibody in sera from patients with systemic lupus erythematosus. J Clin Invest, 1980, 66, 353–360.

    Article  PubMed  CAS  Google Scholar 

  60. Parker, M.D., Mrion, T. Circulating complementfixing immune complexes in mixed connective tissue disease (Abstract). Arthritis Rheum, 1977, 20, 130.

    Google Scholar 

  61. Cunningham, P.H., Andrews, B.S., Davis, J.S. Immune complexes in patients with progressive systemic sclerosis and mixed connective tissue disease. Clin Res, 1978, 26, 374A.

    Google Scholar 

  62. Halla, J.T., Volanakis, J.E., Schrohenloher, R.E. Circulating immune complexes in mixed connective tissue disease. Arthritis Rheum, 1979, 22, 484–489.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section of Rheumatology, Centro Medico Nacional “Marqués de Vadecilla” and School of Medicine, University of Santander, Spain

    J. Calderon, V. Rodriguez-Valverde, S. Sanchez Andrade, J. L. Riestra & J. Gomez-Reyno

  2. The Service of Rheumatology, Ciudad Sanitaria 1° de Octubre, Madrid, Spain

    J. Calderon, V. Rodriguez-Valverde, S. Sanchez Andrade, J. L. Riestra & J. Gomez-Reyno

Authors
  1. J. Calderon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. Rodriguez-Valverde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Sanchez Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. L. Riestra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Gomez-Reyno
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Calderon, J., Rodriguez-Valverde, V., Andrade, S.S. et al. Clinical profiles of patients with antibodies to nuclear ribonucleoprotein. Clin Rheumatol 3, 483–492 (1984). https://doi.org/10.1007/BF02031271

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02031271

Key words

Search

Navigation