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. 2008 Jul 11;22(4):271–277. doi: 10.1002/jcla.20248

Anti‐histones antibodies in systemic lupus erythematosus: prevalence and frequency in neuropsychiatric lupus

Xiao‐Yun Sun 1,†, Jinxia Shi 1,‡, Lei Han 1, Yin Su 1, Zhan‐Guo Li 1,✉
PMCID: PMC6649061  PMID: 18634076

Abstract

To investigate the specificity, sensitivity, and concomitant presence of antibodies against histones (H), histone H1 (H1), and histone H3 (H3) in patients with systemic lupus erythematosus (SLE) and analyze their association with SLE. Serum IgG anti‐histones antibodies were detected by enzyme‐linked immunosorbent assay in 144 SLE patients consisting of 24 neuropsychiatric lupus (NPSLE), 65 lupus nephritis (LN), and 55 SLE, 100 other rheumatic diseases patients, as well as 40 healthy controls. Clinical and biological parameters of the patients were also evaluated. Anti‐H, anti‐H1, and anti‐H3 antibodies yielded a sensitivity of approximately 33% and a specificity of more than 93% for SLE, which was comparable to that found for anti‐double‐stranded DNA (anti‐dsDNa) antibodies. More significantly, anti‐histone antibody is found in approximately 50% of patients with NPSLE compared with LN. Moreover, the titers of anti‐histones antibodies of NPSLE patients were significantly higher than that of patients with SLE and LN. The sequential analysis revealed a close correlation of anti‐H and anti‐H1 antibodies with SLE disease activity. There was an approximate 30% positive rate of anti‐histones antibodies in 144 SLE patients lacking anti‐nucleosome, anti‐mDNA, anti‐Sm, and anti‐dsDNA antibodies. Antibodies to histones H1 and H3 are markers with high specificity of 93.6–96.4% for SLE. The anti‐histone antibody markers are prevalent in approximately 50% of NPSLE. Furthermore, there was a strong correlation with SLE disease activity index and levels of antibodies to histones and H1. J. Clin. Lab. Anal. 22:271–277, 2008. © 2008 Wiley‐Liss, Inc.

Keywords: autoantibody, histones, systemic lupus erythematosus, neuropsychiatric lupus

REFERENCES

  • 1. Tan EM. An immunologic precipitin system between soluble nucleo‐protein and serum antibody in systemic lupus erythematosus. J Clin Invest 1967;46;735–745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Tan EM. Antinuclear antibodies: Diagnostic markers for autoimmune diseases and probe for cell biology. Adv Immunol 1989;44:93–151. [DOI] [PubMed] [Google Scholar]
  • 3. Wallace DJ, Hahn BH, Quismorio FP, et al. 2007. Dubois' Lupus Erythematosus. Philadelphia, PA: Lea & Febinger; p 464–479. [Google Scholar]
  • 4. Pisetsky DA. Anti‐DNA antibodies in systemic lupus erythematosus. Rheum Dis Clin North Am 1992;18:437–454. [PubMed] [Google Scholar]
  • 5. Fritzler MJ, Tan EM. Antibodies to histones in drug‐induced and idiopathic lupus erythematosus. J Clin Invest 1978;62;560–567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Gioud M, Ait Kaci M, Monier JC. Histone antibodies in systemic lupus erythematosus. A possible diagnostic tool. Arthritis Rheum 1982;25:407–413. [DOI] [PubMed] [Google Scholar]
  • 7. Chabre H, Amoura Z, Piette JC, et al. Presence of nucleosome restricted antibodies in patients with systemic lupus erythematosus. Arthritis Rheum 1995;38:1485–1491. [DOI] [PubMed] [Google Scholar]
  • 8. Mohan C, Adams S, Stanik V, et al. Nucleosome: A major immunogen for pathogenic autoantibody‐inducing T cells of lupus. J Exp Med 1993;177:1367–1381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Burlingame RW, Boey ML, Starkebaum G, et al. The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. J Clin Invest 1994;94;184–192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Lefkowitz JB, Kiehl M, Rubenstein J, et al. Heterogeneity and clinical significance of glomerular‐binding antibodies in systemic lupus erythematosus. J Clin Invest 1996;98;1373–1380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. van Bruggen MC, Kramers C, Walgreen B, et al. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis. Nephrol Dial Transplant 1997;12:57–66. [DOI] [PubMed] [Google Scholar]
  • 12. Kramers C, Hylkema MN, van Bruggen MC, et al. Anti‐nucleosomal antibodies complexed to nucleosomal antigens show anti‐dsDNA reactivity and bind to rat glomerular basement membrane in vivo. J Clin Invest 1994;94;568–577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Elouaai F, Lule L, Benoist H, et al. Anti‐histone antibodies are concentrated in glomerular eluates of lupus mice. Nephrol Dial Transplant 1994;9:362–366. [PubMed] [Google Scholar]
  • 14. González C, Garcia‐Berrocal B, Herráez O, et al. Anti‐nucleosome, anti‐chromatin, anti‐dsDNA and anti‐histone antibody reactivity in systemic lupus erythematosus. Clin Chem Lab Med 2004;42:266–272. [DOI] [PubMed] [Google Scholar]
  • 15. Cortés‐Hernández J, Ordi‐Ros J, Labrador M, et al. Antihistone and anti‐double‐stranded deoxyribonucleic acid antibodies are associated with renal disease in systemic lupus erythematosus. Am J Med 2004;116:165–173. [DOI] [PubMed] [Google Scholar]
  • 16. Lakatos A, Sétáló J, Jobst K, et al. Relationship of serum antihistone antibody level to the patient's age. Acta Med Hung 1992–1993;49:91–100. [PubMed] [Google Scholar]
  • 17. Gompertz NR, Isenberg DA, Turner BM. Correlation between clinical features of systemic lupus erythematosus and levels of antihistone antibodies of the IgG, IgA, and IgM isotypes. Ann Rheum Dis 1990;49:524–527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997;40:1725. [DOI] [PubMed] [Google Scholar]
  • 19. Bombardier C, Gland DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI: A disease activity index for lupus patients. Arthritis Rheum 1992;35:630–640. [DOI] [PubMed] [Google Scholar]
  • 20. Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1982;25:1271–1277. [DOI] [PubMed] [Google Scholar]
  • 21. Schett G, Rubin RL, Steiner G, et al. The lupus erythematosus cell (LEC) phenomenon: Comparative analysis of anti‐chromatin antibody specificity in LEC positive and LEC negative sera. Arthritis Rheum 2000;43:420–428. [DOI] [PubMed] [Google Scholar]
  • 22. Chen HY, Jia RL, Li ZG. Significance of anti‐cell membrane‐associated DNA (mDNA) antibodies in systemic lupus erythematosus. Chin J Rheumatol 2005;9:229–233. [DOI] [PubMed] [Google Scholar]
  • 23. Suzuki T, Burlingame RW, Casiano CA, et al. Antihistone antibodies in systemic lupus erythematosus: Assay dependency and effects of ubiquitination and serum DNA. J Rheumatol 1994;21:1081–1091. [PubMed] [Google Scholar]
  • 24. Viard JP, Choquette D, Chabre H, et al. Anti‐histone reactivity in systemic lupus erythematosus sera: A disease activity index linked to the presence of DNA:anti‐DNA immune complexes. Autoimmunity 1992;12:61–68. [DOI] [PubMed] [Google Scholar]
  • 25. Cohen MG, Webb J. Antihistone antibodies in rheumatoid arthritis and Felty syndrome. Arthritis Rheum 1989;32:1319–1324. [DOI] [PubMed] [Google Scholar]
  • 26. Sato S, Ihn H, Kikuchi K, et al. Antihistone antibodies in systemic sclerosis. Arthritis Rheum 1994;37:391–394. [DOI] [PubMed] [Google Scholar]
  • 27. Cervera R, Vinas O, Ramos‐Casals M, et al. Anti‐chromatin antibodies in systemic lupus erythematosus: A useful marker for lupus nephropathy. Ann Rheum Dis 2003;62:431–434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Kubo M, Ihn H, Yazawa N, et al. Prevalence and antigen specificity of anti‐histone antibodies in patients with polymyositis/dermatomyositis. J Invest Dermatol 1999;112:711–715. [DOI] [PubMed] [Google Scholar]
  • 29. Fritzler MJ, Ryan P, Kinsella TD. Clinical features of systemic lupus erythematosus patients with antihistone antibodies. J Rheumatol 1982;9:46–51. [PubMed] [Google Scholar]
  • 30. Epstin A, Greeberg M, Halpert S, et al. The clinical application of an ELISA technique for the detection of antihistone antibodies. J Rheumatol 1986;13:304–307. [PubMed] [Google Scholar]
  • 31. Muller S, Barakat S, Watts R, et al. Longitudinal analysis of antibodies to histones, Sm‐D peptides and ubiquitin in the serum of patients with systemic lupus erythematosus, rheumatoid arthritis and tuberculosis. Clin Exp Rheumatol 1990;8:445–453. [PubMed] [Google Scholar]
  • 32. Bernstein RM, Hobbs RN, Lea DJ, et al. Patterns of antihistone antibody specificity in systemic rheumatic disease. Arthritis Rheum 1985;28:285–293. [DOI] [PubMed] [Google Scholar]
  • 33. Gioud M, Aitkaci A, Monier JC. Histone antibodies in systemic lupus erythematosus. Arthritis Rheum 1982;25:407–413. [DOI] [PubMed] [Google Scholar]
  • 34. Klajman A, Kafri B, Shohat T, et al. The prevalence of antibodies to histones induced by procainamide in old people, in cancer patients and in rheumatoid‐like disease. Clin Immunol Immunopathol 1983;27:1–8. [DOI] [PubMed] [Google Scholar]
  • 35. Fishbein E, Alarcon‐Segovia D, Vega JM. Antibodies to histones in systemic lupus erythematosus. Clin Exp Immunol 1979;36:145–150. [PMC free article] [PubMed] [Google Scholar]
  • 36. Aitkaci A, Monier JC, Mamelle N. Enzyme‐linked immunosorbent assay for antihistone antibodies and their presence in systemic lupus erythematosus sera. J Immunol Methods 1981;44:411–422. [DOI] [PubMed] [Google Scholar]
  • 37. Cohen MG, Pollard KM, Webb J. Antibodies to histone in systemic lupus erythematosus: Prevalence, specificity, and relationship to clinical and laboratory features. Ann Rheum Dis 1992;51:61–66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Sxhett G, Smmolen J, Zimmermann C, et al. The autoimmune response to chromatin antigens in systemic lupus erythematosus; autoantibodies against histone H1 are a highly specific marker for SLE associated with increased disease activity. Lupus 2002;11:704–715. [DOI] [PubMed] [Google Scholar]
  • 39. ACR Ad Hoc Committee on Neuropyschiatric Lupus Nomenclature . The Americang college of rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999;42:599–608. [DOI] [PubMed] [Google Scholar]

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