Summary
The cellular regulation of anti-nuclear ribonucleoprotein (nRNP) antibody synthesis in patients with systemic lupus erythematosus (SLE) was examined and compared with that of anti-double-stranded DNA (dsDNA) antibodies. In vitro antibody production by lymphocytes from SLE patients with antibodies to either dsDNA or nRNP alone was measured using dsDNA-specific and nRNP-specific solid-phase radioimmunoassays (RIA). Lymphocytes of SLE patients with only anti-dsDNA antibodies and normal individuals failed to synthesize anti-nRNP antibody with or without nRNP stimulation. In contrast, lymphocytes from SLE patients with anti-nRNP antibody alone in their sera synthesized in vitro a large amount of anti-nRNP antibody with or without nRNP stimulation. Experiments with reconstituted autologous lymphocytes indicated that B cells and T cells were required for anti-nRNP antibody synthesis. As expected, helper function for antibody synthesis by autologous B cells resided in the T4-cell population and suppressor function in the T8-cell population. T8 cells from SLE patients with anti-nRNP antibody alone suppressed anti-nRNP antibody synthesis by autologous B cells irrespective of clinical activity. This is in contrast to anti-dsDNA antibody production, which was not suppressed by autologous T8 cells. These results indicate that the cellular regulation of anti-nRNP antibody synthesis in SLE is different from that of anti-dsDNA antibody syntheis. Increased anti-nRNP antibody synthesis may be due to increased T4-helper cell function rather than defective T8-suppressor function.
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Kunkel HG, Tan EM (1964) Autoantibodies and disease. Adv Immunol 4:355–362
Sharp GC, Irvin WS, May CM, Holman HR, McDuffie FC, Hess EV, Schmid FR (1976) Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective tissue disease, systemic lupus erythematosus and other rheumatic diseases. N Engl J Med 295:1149–1154
Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease — an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52:148–159
Sharp GC (1982) Subsets of SLE and mixed connective tissue disease. Am J Kidney Dis 11:201–205
Jones MB, Osterholm RK, Wilson RB, Martin FH, Commers JR, Bachmyer JD (1978) Fatal pulmonary hypertension and resolving immune-complex glomerulonephritis in mixed connective tissue disease. Am J Med 65:855–863
Sullivan WD, Hurst DJ, Harmon CE, Esther JH, Agia GA, Maltby JD, Lillard SB, Held CN, Wolfe JF, Sunderrajan EV, Maricq HR, Sharp GC (1984) A prospective evaluation emphasizing pulmonary involvement in patients with mixed connective tissue disease. Medicine 63:92–107
Agia GA, Reddy VC, Maithy JD, Sandok K, Hurst DJ, (1980) Pulmonary involvement in MCTD. Am Rev Respir Dis 121:105A
Takeuchi T, Abe T, Koide J, Hosono O, Morimoto C, Homma M (1984) Cellular mechanism of DNA-specific antibody synthesis by lymphocytes from systemic lupus erythematosus. Arthritis Rheum 27:766–773
Tan EM, Cohen AS, Fries JF, Masi AT, McShine D, Rothfield NF, Schalder JF, Talal N, Winchester R (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1276
Sharp GC, Irvin WS, LaRoque RL, Velez C, Daly V, Kaiser AD, Holman HR (1971) Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy. J Clin Invest 50:350–359
Ledbetter JA, Evan RL, Lipinski M, Cummingham-Rundles C, Good RA, Herzenberg LA (1981) Evolutionary conservation of surface molecules that distinguish T lymphocytes helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med 153:310–323
Reinherz EL, Kung PC, Goldstein G, Schlossman SF (1979) A monoclonal antibody with selective reactivity with functionally mature thymocytes and all peripheral human T cells. J Immunol 123:1312–1317
Stashenko P, Nadler LM, Hardy R, Schlossman SF (1980) Characterization of human B lymphocyte specific antigen. J Immunol 125:1678–1685
Todd RF, Nadler LM, Schlossman SF (1981) Antigens on human monocytes identified by monoclonal antibodies. J Immunol 126:1435–1442
Takano M, Golden SS, Sharp GC, Agris PF (1981) Molecular relationships between two nuclear antigens, ribonucleoprotein and Sm: purification of active antigens and their biochemical characterization. Biochemistry 20:5929–5935
Takeuchi T (1985) Spontaneous production of antibodies to deoxyribonucleic acids in patients with systemic lupus erythematosus. Clin Immunol Immunopathol 35:47–56
Talal N, Pillarisetty RJ, DeHoratius RJ, Messner RP (1976) Immunological regulation of spontaneous antibodies to DNA and RNA. Clin Exp Immunol 25:377–382
Nakano, Tanimoto K, Moroi Y, Miyamoto T (1985) Detection of anti-nucleoprotein (nRNP) antibody producing cells in peripheral blood lymphocytes from patients with mixed connective tissue disease. J Rheumatol 12:924–927
Ohsone Y, Akizuki M, Hirakata M, Satoh M, Yamagata H, Homma M (1986) In vitro production of autoantibodies to U1 ribonucleoprotein by peripheral blood mononuclear cells from patients with connective tissue disease. Arthritis Rheum 29:1343–1350
Sakane T, Steinberg AD, Green I (1978) Studies of immune functions of patients with systemic lupus erythematosus. I. Dysfunction of suppressor T-cell activity related to impaired generation of, rather than response to, suppressor cells. Arthritis Rheum 21:657–664
Koide J, Takano M, Takeuchi T, Hosono O, Amano K, Homma M, Abe T (1986) Direct demonstration of immunoregulatory T cell defects in patients with systemic lupus erythematosus. Scand J Immunol 23:449–459
Alarcón-Segovia D, Ruiz-Arguelles A (1980) Suppressor cell loss and dysfunction in mixed connective tissue disease. Arthritis Rheum 23:314–318
Alarcón-Segovia D, Palacios R (1981) Human post-thymic precursor cells in health and disease. IV. Abnormalities in immunoregulatory T cell circuits in mixed connective tissue disease. Arthritis Rheum 24:1486–1494
Palacios R, Alarcón-Segovia D, Llorente L, Ruiz-Arguelles A, Diaz-Jouanen E (1981) Human post-thymic precursor cells in health and disease. I. Characterization of the autologous rosette-forming T cells as post-thymic precursors. Immunology 42:127–135
Katz DH, Graves M, Dorf ME, Dimuzio H, Benacerraf B (1975) Cell interactions between histocompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex. J Exp Med 141:263–268
Koide J, Abe T, Takeuchi T, Hosono O, Amano K, Homma M (1984) Abnormalities of B cell stimulatory factors (BSF) produced by T cells and B cell response to BSF in patients with SLE. Jpn J Clin Immunol 7:208–215
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Hosono, O., Takeuchi, T., Koide, J. et al. Cellular regulation of anti-nRNP antibody synthesis is different from that of anti-DNA antibody synthesis in patients with systemic lupus erythematosus. Rheumatol Int 8, 177–183 (1988). https://doi.org/10.1007/BF00270457
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DOI: https://doi.org/10.1007/BF00270457