Acta Univ. Palacki. Olomuc., Fac. Med. Volume 144, 2000 | DOI: 10.5507/bp.2000.015

ANTI-NUCLEOSOME ANTIBODIES – A NOVEL TEST IN SYSTEMIC LUPUS ERYTHEMATOSUS

Pavel Horáka, Zuzana Heřmanováb, Vlastimil ©čudlaa, Ladislav Faltýneka, Zdeněk Pospíąila
a III. Department of Internal Medicine, University of Olomouc, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic,
b Department of Clinical Immunology, University of Olomouc, I. P. Pavlova 6, 775 20 Olomouc, Czech Republic.

In this study the serum levels of specific anti-nucleosome autoantibodies (autoAb) were measured in the followup of the group of SLE patients and compared to the levels of anti-dsDNA, C3, C4 components of complement, toECLAM- European Lupus Activity Measure and to the levels of sVCAM-1, sICAM-1, neopterin, sIL-2r, IL-10 andfas ligand. Anti-nucleosome antibodies were detected using an enzyme immunoassay for the quantitative determinationof autoAb to nucleosomes and their components in the human serum in the group of 52 patients, 50 of themfemale, who all fulfilled criteria of SLE according to ACR (American Colledge of Rheumatology). Anti-nucleosomeantibodies were followed up during 3 subsequent measurements during six months and compared to the developmentof ECLAM index, the levels of anti ds-DNA antibodies and C3, C4 complement components levels and otheractivity markers.The probands with the stable low disease activity had the lowest levels of anti-nucleosome Ab (83 ±33.0 IU/ml).The patients with the stable high or increasing activity had the mean titers in the first series 200.42 ±36 IU/ml and192 ±65 IU/ml and 188±58.11 IU/ml in the 2. and 3. serial measurement. Subgroup with the high starting activityand with decrease of the activity index had the mean levels of 223 ±39.0IU/ml, 185.6 ±37.6 IU/ml and 207 ±55.5 IU/mlduring three measurements. In the subgroup of patients with lupus nephritis (LN) n=15, the anti-nucleosome Ablevels were 176 ±34.0 IU/ml, 174 ±30.0 IU/ml and 148±32.0 IU/ml. A strong correlation was found between levelsof anti-nucleosome and anti-dsDNA antibodies. All sera with anti-dsDNA antibodies over 40 had at the same timepositive titer of anti-nucleosome antibodies, however, 21 sera with negative anti-dsDNA had positive test for antinucleosomeantibodies. Anti-nucleosome antibodies correlated with ECLAM activity index and reversibly with C4.No correlation was established with levels of C3, sVCAM-1, sICAM-1, IL-10, fas ligand, neopterin and sIL2r. Theexamination of anti-nucleosome Ab contributes to the early diagnosis and is an instrument in the differentialdiagnosis of the connective tissue diseases and it seems to be especially valuable in anti-dsDNA negative lupus. Theuse of anti-nucleosome antibodies measurement as a marker of disease activity deserves further evaluation.

Keywords: Systemic lupus erythematosus (SLE), Anti-nucleosome antibodies, ECLAM index, Thrombomodulin

Published: December 1, 2000  Show citation

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Horák, P., Heřmanová, Z., ©čudla, V., Faltýnek, L., & Pospíąil, Z. (2000). ANTI-NUCLEOSOME ANTIBODIES – A NOVEL TEST IN SYSTEMIC LUPUS ERYTHEMATOSUS. Biomedical papers144(144), 27-32. doi: 10.5507/bp.2000.015
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References

  1. Gilbert, D., Brard, F., Jovelin, F., Tron, F. (1996) Do naturally accurring autoantibodies participate in the constitution of the pathological B-cell repertoire in systemic lupus erythematosus? J. Autoimmun., 9, 247-257. Go to original source... Go to PubMed...
  2. Amoura, Z., Piette, J. Ch., Bach, J. F., Koutouzov, S. (1999) The key role of nucleosomes in Lupus. Arthritis Rheum., 42, 833-843. Go to original source... Go to PubMed...
  3. Vlahakos, D. V., Foster, M. H., Adams, S., Katz, M., Ucci, A. A., Barrett, K. J., Datta, S. K., Madaio, M. P. (1992) Anti-DNA antibodies form immune deposits at distinct glomerular and vascular sites. Kidney Int., 41, 1690-1700. Go to original source... Go to PubMed...
  4. Izui, S., Lambert, P. H., Miescher, P. A. (1977) Failure to detect circulating DNA-anti-DNA complexes by four radioiminological methods in patients with systemic lupus erythematosus. Clin. Exp. Immunol., 30, 384-392.
  5. Bernstein, K. A., Di Valerio, R., Lefkowith, J. B. (1995). Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex. J. Immunol., 154, 2424-2433. Go to original source... Go to PubMed...
  6. Emlen, W., Niebur, J., Kadera, R. (1994). Accelerated in vitro apoptosis of lymphocytes from patients with systemic lupus erythematosus. J. Immunol., 152, 3685-3692. Go to original source... Go to PubMed...
  7. Williams jr., R. C., Malone, C., Blood, B., Silvestris, F. (1999) Anti-DNA and antinucleosome antibody affinity - a mirror image of lupus nephritis? J. Rheumatol., 26, 331-346. Go to PubMed...
  8. Brard, F., Gilbert, D., Jovelin, F., Tron, F. (1997) Idiopatic analysis of antinucleosome monoclonal antibodies derived from lupus mice. J. Autoimmun., 10, 425-431. Go to original source... Go to PubMed...
  9. Suenaga, R., Mitamura, K., Abdou, N. I. (1998) Isolation of antinucleosome antibodies from the plasma of lupus nephritis patients. Clin. Rheumatol., 17, 189-194. Go to original source... Go to PubMed...
  10. Bavykin, S. G., Usachenko, S. I., Zalensky, A. O., Mirzabekov, Z. (1990) Structure of nucleosomes and organization of internucleosomal DNA in chromatin. J. Mol. Biol., 212, 595-611. Go to original source... Go to PubMed...
  11. Burlingame, R. W., Rubin, R. L., Balderas, R. S., Theofilopoulos, A. N. (1993) Genesis and evolution of antichromatin autoantibodies in murine lupus indicates T-dependent immunization with self antigen. J. Clin. Invest., 91, 1687-1696. Go to original source... Go to PubMed...
  12. Amoura, Z., Chabre, H., Koutouzov, S., Lotton, C., Cabrespines, A., Bach, J. F., Jacob, L. (1994) Nucleosome restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria. Arthritis Rheum., 37, 1684-1688. Go to original source... Go to PubMed...
  13. Kramers, C., Chabre, H., Koutouzov, S., Lotton, C., Cabrespines, A., Bach, J. F., Jacob, L. (1994) Antinucleosome antibodies complexed to nucleosome antigens show anti-DNA reactivity and bind to rat glomerular membrane in vivo. J. Clin. Invest., 92, 568-580. Go to original source... Go to PubMed...
  14. Amoura, Z., Koutouzov, S., Chabre, H., Cacoub, P., Amoura, I., Musset, L., Bach, J. F., Piette, J. C. (2000) Presence of antinucleosome autoantibodies in a restricted set of connective tissue diseases. Arthritis Rheum., 43, 76-84. Go to original source... Go to PubMed...
  15. Bencivelli, W., Vitali, C., Isenberg, D. A., Smolen, J. S., Snaith, M. L., Sciuto, M., Bombardieri, S. (1992) and European Consensus Study Group for Disease Activity in SLE: Disease activity in SLE: Report of the consensus study group of the European workshop fpr rheumatology research. III. Development of the computerised clinical chart and its appplication to the comparison of different indices of disease activity. Clin. Exp. Rheumatol., 10, 549-554. Go to PubMed...
  16. Tan, E. M., Cohen, A. S., Fries, J. F., Masi, A. T., McShane, D. J., Rothfield, N. F., Schaller, J. G., Talal, N., Winchester, R. J. (1982) The 1982 revised criteria for the classification of systemic lupus erythmatosus. Artritis Rheum., 25, 1271-1277. Go to original source...
  17. Lefkowith, J. B., Gilkeson, G. S. (1996) Nephritogenic autoantibodies in lupus: current concepts and antinuing controversies. Arthritis Rheum., 39, 894-903. Go to original source... Go to PubMed...
  18. Lefkowith, J. B., Kiehl, M., Rubenstein, J., DiValerio, R., Bernstein, K., Kahl, L., Rubin, R. L., Gourley, M. (1996) Heterogeneity and Clinical Significance of Glomerular-binding Antibodies in Systemic Lupus Erythematosus. J. Clin. Invest., 98, 1373-1380. Go to original source... Go to PubMed...
  19. Madaio, M. P., Hodder, S., Schwartz, R. S., Stollar, B. D. (1984) Responsiveness of autoimmune and normal mice to nucleic acid antigens. J. Immunol., 132, 872-882. Go to original source... Go to PubMed...
  20. Burlingame, R. W., Boye, M. L., Starkebaum, G., Rubin, R. L. (1994) The central role of chromatin in autoimmune responces to histones and DNA in systemic lupus erythematosus. J. Clin. Invest., 94, 184-192. Go to original source... Go to PubMed...