Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to proliferating cell nuclear antigen in active lupus patients

  • 39 Accesses

  • 24 Citations

Abstract

Hybridoma producing monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) (TOB7, IgG1 κ) was newly established. Using TOB7, PCNA was detected in the peripheral blood mononuclear cells (PBMC) in patients with systemic lupus erythematosus (SLE). Forty-four of 58 patients with SLE had PBMC expressing PCNA. The percentage of PCNA-positive PBMC in patients with SLE was 0–20% (mean: 2.63%) which was significantly higher (P<0.01) compared with normal controls (mean: 0.18%), patients with rheumatoid arthritis (mean: 0.83%), and patients with mixed connective tissue disease (mean: 0.38%). Patients with high numbers of PCNA positive PBMC tended to complicate pulmonary disorders (P<0.005), especially pulmonary fibrosis (P<0.005). In addition, the percentage of PCNA-positive cells in SLE patients correlated with the disease activity (r=0.45,P<0.01). The lymphocyte subsets of PCNA-positive PBMC were examined, and most of those cells belonged to CD4- or CD8-positive T-cell populations in three lupus patients. Our findings indicate that PCNA-positive activated PBMC are present in SLE patients and the percentage of PCNA-positive PBMC may be used as an indicator of disease activity.

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

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

References

  1. 1.

    Miyachi K, Fritzler MJ, Tan EM: Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121:2228–2234, 1978

  2. 2.

    Fritzler MJ, McCarty GA, Ryan JP, Kinsella TD: Clinical features of patients with antibodies directed against proliferating cell nuclear antigen. Arth Rheum 26:140–145, 1983

  3. 3.

    Ohata N: Clinical significance of antibodies to proliferating cell nuclear antigen. Rheumachi 27:79–87, 1987

  4. 4.

    Takasaki Y, Fishwild D, Tan EM: Characterization of proliferating cell nuclear antigen recognized by autoantibodies in lupus sera. J Exp Med 159:981–992, 1984

  5. 5.

    Ogata K, Ogata Y, Nakamura RM, Tan EM: Purification and N-terminal amino acid sequence of proliferating cell nuclear antigen (PCNA)/cyclin and development of ELISA for anti-PCNA antibodies. J Immunol 135:2623–2627, 1985

  6. 6.

    Takasaki Y, Deng JS, Tan EM: A nuclear antigen associated with cell proliferation and blast transformation. J Exp Med 154:1899–1909, 1981

  7. 7.

    Mathews MB, Bernstein RM, Franza BR Jr, Garrels JI: Identity of the proliferating cell nuclear antigen and cyclin. Nature 309:374–376, 1984

  8. 8.

    Bravo R, Frank R, Blundell PA, Bravo HM: Cyclin/PCNA is the auxiliary protein of DNA polymerase-δ. Nature 326:515–517, 1987

  9. 9.

    Prelich G, Tan CK, Kostura M, Mathews MB, So AG, Downey KM, Stillman B: Functional identity of proliferating cell nuclear antigen and a DNA polymerase-δ auxiliary protein. Nature 326:517–520, 1987

  10. 10.

    Smetana K, Gyorkey F, Chan PK, Tan EM: Proliferating cell nuclear antigen (PCNA) and human malignant tumor nuclear antigen (HMTNA) in nucleoi of human hematological malignancies. Blut 46:133–141, 1983

  11. 11.

    Takasaki Y, Robinson WA, Tan EM: Proliferating cell nuclear antigen in blast crisis cells of patients with chronic myeloid leukemia. J Natl Cancer Inst 73:655–661, 1984

  12. 12.

    Ogata K, Kurki P, Celis JE, Nakamura RM, Tan EM: Monoclonal antibody to a nuclear protein (PCNA/cyclin) associated with DNA replication. Exp Cell Res 168:475–486, 1987

  13. 13.

    Kurki P, Ogata K, Tan EM: Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immnol Methods 109:49–59, 1988

  14. 14.

    Thaete LG, Ahnen DJ, Malkinson AM: Proliferating cell nuclear antigen (PCNA/Cyclin) immunocytochemistry as a labeling index in mouse lung tissues. Cell Tissue Res 256:167–173, 1989

  15. 15.

    Kurki P, Ogata K, Robinson CA, Williams GW, Tan EM: Proliferating cell nuclear antigen (PCNA) as a marker for a subset of activated human T-lymphocytes in blood and synovial fluid. Arth Rheum 29:586 (abstr B 24), 1986

  16. 16.

    Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schallen JG, Talal N, Winchester RJ: The 1982 revised criteria for the classification of systemic lupus erythematosus. J Clin Invest 76:1865–1870, 1985

  17. 17.

    Ropes MW, Bennett EA, Cobb S, Jacox R, Jessary R: 1958 revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis 9:175–179, 1958

  18. 18.

    Lahita RG, Bradlow HL, Ginzler E, Pang S, New M: Low plasma androgens in women with systemic lupus erythematosus. Arth Rheum 30:241–248, 1987

  19. 19.

    Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR: Mixed connective tissue disease: An apparently distinct rheumatic disease syndrome associated with a specific antibody to extractable nuclear antigen (ENA). Am J Med 52:148–157, 1972

  20. 20.

    Oi V, Herzenberg LA:In Selected Methods in Cellular Immunology, BB Mishell, E Shigii (eds). San Francisco, WH Freeman, 1980, p 351

  21. 21.

    Boyum A: Separation of leukocytes from blood and bone marrow. Scand J Clin Lab Invest 21:97–105, 1968

  22. 22.

    Campbell DH, Garvey FS, Cremer NE, Sussdorf DH: Preparation of fluorescein-conjugated gamma globulin.In Methods in Immunology. New York, WA Benjamin, 1970, p 351

  23. 23.

    Farr RS: A quantitative immunochemical measure of the primary interaction between I*BSA and antibody. J Infect Dis 103:239–262, 1958

  24. 24.

    Northway JD, Tan EM: Differentiation of antinuclear antibodies giving speckled staining patterns in immunofluorescence. Clin Immunol 1:140–154, 1972

  25. 25.

    Lowry OH, Rosebrough NJ, Farr AL: Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275, 1951

  26. 26.

    Jasin HE, Ziff M: Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. Arth Rheum 18:219–228, 1975

  27. 27.

    Letwin DA, Cohen PL, Winfield JB: Characterization of warm-reactive IgG anti-lymphocyte antibody in systemic lupus erythematosus. Relative specificity for mitogenactivated T cells and their soluble products. J Immunol 130:181–186, 1983

  28. 28.

    Fu SM, Chiroazzi N, Wang CY, Montaxeri G, Kunkel HG, Ko HS, Gottlieb AB: Ia bearing T lymphocytes in man: Their identification and role in the generation of allogenic helper activity. J Exp Med 148:1423–1428, 1978

  29. 29.

    Trowbridge IS, Omary MB: Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci USA 78:3039–3043, 1981

  30. 30.

    Uchiyama T, Broder S, Waldman TA: A monoclonal antibody (anti-Tac) reactive with activated and functional mature human T cells. I. Production of anti-Tac monoclonal antibody and distribution of Tac cells. J Immunol 126:1393–1397, 1981

  31. 31.

    Boumpas DT, Tsokos GC, Mann DL, Eleftheriades EG, Harrs CC, Mark GE: Increased proto-oncogene expression in peripheral blood lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases. Arth Rheum 29:755–760, 1986

  32. 32.

    Gerdes J, Schwab U, Lemke H, Stein H: Production of a mouse monoclonal antibody reactive with a nuclear antigen associated with cell proliferation. Int J Cancer 31:13–18, 1983

  33. 33.

    Haynes, BF, Hemler ME, Mann DL, Eisenbarth GS, Shelhamer J, Mostowski HS, Thomas CA, Strominger JL, Fauci AS: Characterization of a monoclonal antibody (4F2) that binds to human monocytes and to a subset of activated lymphocytes. J Immunol 126:1409–1413, 1981

  34. 34.

    Yu DTY, Winchester RJ, Fu SM, Gibofsky A, Ko HS, Kunkel HG: Peripheral blood Ia-positive T cells. J Exp Med 151:91–100, 1980

  35. 35.

    Kurki P, Lotz M, Ogata K, Tan EM: Proliferating cell nuclear antigen (PCNA)/cyclin in activated human T lymphocytes. J Immunol 138:4114–4120, 1987

  36. 36.

    Volk HD, Kopp J, Korner IJ, Jahn S, Grunow R, Barthelmes H, Fiebig H: Correlation between the phenotype and the functional capacity of activated T cells in patients with active systemic lupus crythematosus. Scand J Immunol 24:109–114, 1986

  37. 37.

    Cotner T, Williams JM, Christenson L, Shapiro HM, Strom TB, Strominger J: Simultaneous flow cytemetric analysis of human T cell activation antigen expression and DNA content. J Exp Med 157:461–472, 1983

  38. 38.

    Blaese RM, Grayson J, Steinberg AD: Increased immunoglobulin-secreting cells in the blood of patients with active systemic lupus erythematosus. Am J Med 69:345–350, 1980

  39. 39.

    Hirano T: The appearance of Ia+T cells in systemic lupus erythematosus.In Cellular, Molecular and Genetic Approaches to Immunodiagnosis and Immunotherapy, K Kano (ed). Tokyo, University of Tokyo Press, 1987, pp 441–445

  40. 40.

    Carney WP, Iacovicello V, Hirsch MS: Functional properties of T lymphocytes and their subsets in cytomegalovirus mononucleosis. J Immunol 130:390–393, 1983

  41. 41.

    Crawford DH, Brickell, P, Tidman N, McConnell I, Hoffband AV, Janossy G: Increased numbers of cells with suppressor T cell phenotype in peripheral blood of patients with infectious mononucleosis. Clin Exp Immunol 43:291–297, 1981

  42. 42.

    Prelich G, Kostura M, Marshak DR, Mathews MB, Stillman B: The cell-cycle regulated proliferating cell nuclear antigen is required for SV40 DNA replication in vitro. Nature 326:471–475, 1987

Download references

Author information

Correspondence to Yoshinari Takasaki.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Murashima, A., Takasaki, Y., Ohgaki, M. et al. Activated peripheral blood mononuclear cells detected by murine monoclonal antibodies to proliferating cell nuclear antigen in active lupus patients. J Clin Immunol 10, 28–37 (1990). https://doi.org/10.1007/BF00917495

Download citation

Key word

  • Systemic lupus erythematosus
  • proliferating cell nuclear antigen (PCNA)
  • activated lymphocytes
  • monoclonal anti-PCNA antibody