Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 2003 Jun;62(6):556–560. doi: 10.1136/ard.62.6.556

Anti-dsDNA, anti-Sm antibodies, and the lupus anticoagulant: significant factors associated with lupus nephritis

P Alba 1, L Bento 1, M Cuadrado 1, Y Karim 1, M Tungekar 1, I Abbs 1, M Khamashta 1, D D'Cruz 1, G Hughes 1
PMCID: PMC1754557  PMID: 12759294

Abstract

Background: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial.

Objective: To study the immunological and demographic factors associated with the development of LN.

Patients and methods: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing.

Results: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes.

Conclusions: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN.

Full Text

The Full Text of this article is available as a PDF (106.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Austin H. A., 3rd, Muenz L. R., Joyce K. M., Antonovych T. T., Balow J. E. Diffuse proliferative lupus nephritis: identification of specific pathologic features affecting renal outcome. Kidney Int. 1984 Apr;25(4):689–695. doi: 10.1038/ki.1984.75. [DOI] [PubMed] [Google Scholar]
  2. Ballou S. P., Khan M. A., Kushner I. Clinical features of systemic lupus erythematosus: differences related to race and age of onset. Arthritis Rheum. 1982 Jan;25(1):55–60. doi: 10.1002/art.1780250109. [DOI] [PubMed] [Google Scholar]
  3. Bastian H. M., Roseman J. M., McGwin G., Jr, Alarcón G. S., Friedman A. W., Fessler B. J., Baethge B. A., Reveille J. D., LUMINA Study Group. LUpus in MInority populations: NAture vs nurture Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus. 2002;11(3):152–160. doi: 10.1191/0961203302lu158oa. [DOI] [PubMed] [Google Scholar]
  4. Bell D. A. SLE in the elderly--is it really SLE or systemic Sjögren's syndrome? J Rheumatol. 1988;15(5):723–724. [PubMed] [Google Scholar]
  5. Bell D. A., Smeenk R. J. Clinical connections: assays and assignment. Lupus. 1997;6(3):305–306. doi: 10.1177/096120339700600317. [DOI] [PubMed] [Google Scholar]
  6. Bernstein K. A., Valerio R. D., Lefkowith J. B. Glomerular binding activity in MRL lpr serum consists of antibodies that bind to a DNA/histone/type IV collagen complex. J Immunol. 1995 Mar 1;154(5):2424–2433. [PubMed] [Google Scholar]
  7. Blum A., Rubinow A., Galun E. Predominance of renal involvement in male patients with systemic lupus erythematosus. Clin Exp Rheumatol. 1991 Mar-Apr;9(2):206–207. [PubMed] [Google Scholar]
  8. Brandt J. T., Triplett D. A., Alving B., Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995 Oct;74(4):1185–1190. [PubMed] [Google Scholar]
  9. Catoggio L. J., Skinner R. P., Smith G., Maddison P. J. Systemic lupus erythematosus in the elderly: clinical and serological characteristics. J Rheumatol. 1984 Apr;11(2):175–181. [PubMed] [Google Scholar]
  10. Cervera R., Khamashta M. A., Font J., Sebastiani G. D., Gil A., Lavilla P., Doménech I., Aydintug A. O., Jedryka-Góral A., de Ramón E. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. The European Working Party on Systemic Lupus Erythematosus. Medicine (Baltimore) 1993 Mar;72(2):113–124. [PubMed] [Google Scholar]
  11. Dang H., Harbeck R. J. The in vivo and in vitro glomerular deposition of isolated anti-double-stranded-DNA antibodies in NZB/W mice. Clin Immunol Immunopathol. 1984 Feb;30(2):265–278. doi: 10.1016/0090-1229(84)90061-8. [DOI] [PubMed] [Google Scholar]
  12. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol. 2000 Jun;53(6):424–432. doi: 10.1136/jcp.53.6.424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Farrugia E., Torres V. E., Gastineau D., Michet C. J., Holley K. E. Lupus anticoagulant in systemic lupus erythematosus: a clinical and renal pathological study. Am J Kidney Dis. 1992 Nov;20(5):463–471. doi: 10.1016/s0272-6386(12)70258-5. [DOI] [PubMed] [Google Scholar]
  14. Frampton G., Hicks J., Cameron J. S. Significance of anti-phospholipid antibodies in patients with lupus nephritis. Kidney Int. 1991 Jun;39(6):1225–1231. doi: 10.1038/ki.1991.155. [DOI] [PubMed] [Google Scholar]
  15. García C. O., Molina J. F., Gutiérrez-Ureña S., Scopelitis E., Wilson W. A., Gharavi A. E., Espinoza L. R. Autoantibody profile in African-American patients with lupus nephritis. Lupus. 1996 Dec;5(6):602–605. doi: 10.1177/096120339600500608. [DOI] [PubMed] [Google Scholar]
  16. Harley J. B., Sestak A. L., Willis L. G., Fu S. M., Hansen J. A., Reichlin M. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 1989 Jul;32(7):826–836. [PubMed] [Google Scholar]
  17. Harris E. N. Special report. The Second International Anti-cardiolipin Standardization Workshop/the Kingston Anti-Phospholipid Antibody Study (KAPS) group. Am J Clin Pathol. 1990 Oct;94(4):476–484. doi: 10.1093/ajcp/94.4.476. [DOI] [PubMed] [Google Scholar]
  18. Hochberg M. C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997 Sep;40(9):1725–1725. doi: 10.1002/art.1780400928. [DOI] [PubMed] [Google Scholar]
  19. Homma M., Mimori T., Takeda Y., Akama H., Yoshida T., Ogasawara T., Akizuki M. Autoantibodies to the Sm antigen: immunological approach to clinical aspects of systemic lupus erythematosus. J Rheumatol Suppl. 1987 Jun;14 (Suppl 13):188–193. [PubMed] [Google Scholar]
  20. Isenberg D. A., Garton M., Reichlin M. W., Reichlin M. Long-term follow-up of autoantibody profiles in black female lupus patients and clinical comparison with Caucasian and Asian patients. Br J Rheumatol. 1997 Feb;36(2):229–233. doi: 10.1093/rheumatology/36.2.229. [DOI] [PubMed] [Google Scholar]
  21. Janwityanuchit S., Verasertniyom O., Vanichapuntu M., Vatanasuk M. Anti-Sm: its predictive value in systemic lupus erythematosus. Clin Rheumatol. 1993 Sep;12(3):350–353. doi: 10.1007/BF02231577. [DOI] [PubMed] [Google Scholar]
  22. Joseph J., Anaya J. M., Sandifer M., Scopelitis E., Wilson W., Espinoza L. R. Absence of a distinctive autoantibody profile in black women with lupus nephritis: comment on the article by McCarty et al. Arthritis Rheum. 1994 Aug;37(8):1261–1262. doi: 10.1002/art.1780370825. [DOI] [PubMed] [Google Scholar]
  23. Karim M. Y., Alba P., Tungekar M. F., Abbs I. C., Khamashta M. A., Hughes G. R. V., Hunt B. J. Hypertension as the presenting feature of the antiphospholipid syndrome. Lupus. 2002;11(4):253–256. doi: 10.1191/0961203302lu179cr. [DOI] [PubMed] [Google Scholar]
  24. Kaslow R. A., Masi A. T. Age, sex, and race effects on mortality from systemic lupus erythematosus in the United States. Arthritis Rheum. 1978 May;21(4):473–479. doi: 10.1002/art.1780210412. [DOI] [PubMed] [Google Scholar]
  25. Katz J. B., Limpanasithikul W., Diamond B. Mutational analysis of an autoantibody: differential binding and pathogenicity. J Exp Med. 1994 Sep 1;180(3):925–932. doi: 10.1084/jem.180.3.925. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kaufman L. D., Gomez-Reino J. J., Heinicke M. H., Gorevic P. D. Male lupus: retrospective analysis of the clinical and laboratory features of 52 patients, with a review of the literature. Semin Arthritis Rheum. 1989 Feb;18(3):189–197. doi: 10.1016/0049-0172(89)90061-9. [DOI] [PubMed] [Google Scholar]
  27. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Loizou S., Samarkos M., Norsworthy P. J., Cazabon J. K., Walport M. J., Davies K. A. Significance of anticardiolipin and anti-beta(2)-glycoprotein I antibodies in lupus nephritis. Rheumatology (Oxford) 2000 Sep;39(9):962–968. doi: 10.1093/rheumatology/39.9.962. [DOI] [PubMed] [Google Scholar]
  29. López-Longo F. J., González Fernández C. M., Rodríguez Mahou M., Grau Simó R., Monteagudo Sáez I., Meno García A. C., Carreño Pérez L. Expresión clínica del lupus eritematoso sistémico con anticuerpos anti-U1-RNP y anti-Sm. Rev Clin Esp. 1997 May;197(5):329–335. [PubMed] [Google Scholar]
  30. McCarty G. A., Harley J. B., Reichlin M. A distinctive autoantibody profile in black female patients with lupus nephritis. Arthritis Rheum. 1993 Nov;36(11):1560–1565. doi: 10.1002/art.1780361110. [DOI] [PubMed] [Google Scholar]
  31. Reichlin M., Van Venrooij W. J. Autoantibodies to the URNP particles: relationship to clinical diagnosis and nephritis. Clin Exp Immunol. 1991 Feb;83(2):286–290. doi: 10.1111/j.1365-2249.1991.tb05629.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tápanes F. J., Vásquez M., Ramírez R., Matheus C., Rodríguez M. A., Bianco N. Cluster analysis of antinuclear autoantibodies in the prognosis of SLE nephropathy: are anti-extractable nuclear antibodies protective? Lupus. 2000;9(6):437–444. doi: 10.1191/096120300678828604. [DOI] [PubMed] [Google Scholar]
  33. Wasicek C. A., Reichlin M. Clinical and serological differences between systemic lupus erythematosus patients with antibodies to Ro versus patients with antibodies to Ro and La. J Clin Invest. 1982 Apr;69(4):835–843. doi: 10.1172/JCI110523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wilson W. A., Gharavi A. E., Koike T., Lockshin M. D., Branch D. W., Piette J. C., Brey R., Derksen R., Harris E. N., Hughes G. R. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul;42(7):1309–1311. doi: 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  35. van Venrooij W. J., Charles P., Maini R. N. The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases. J Immunol Methods. 1991 Jul 5;140(2):181–189. doi: 10.1016/0022-1759(91)90369-q. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES