A cross-sectional study of anti-DNA antibodies in the serum and IgG and IgM fraction of healthy individuals,patients with systemic lupus erythematosus and their relatives

Abstract

Sera from healthy individuals, relatives of lupus patients, and lupus patients with active disease and in remission were screened for IgG and IgM antibodies to ssDNA and dsDNA. The serum samples were also separated into IgG and IgM fractions which were screened for DNA reactivity at dilutions equivalent to those used for testing un-fractionated serum.

The results show that whilst, as expected, antibodies of IgG or IgM isotype to both ss and dsDNA could be detected in high concentration in the serum of lupus patients with active disease, anti- ssDNA antibodies of the IgG or IgM isotype are also detectable in healthy individuals, relatives and spouses of lupus patients. Furthermore when IgG and IgM serum fractions were separated and screened for DNA reactivity, the IgM fraction in the healthy individuals frequently showed an increase in the level of binding to ssDNA compared to the serum or separated IgM fraction of SLE relatives. In contrast no increase in DNA reactivity of the IgG fraction was detected in the separated IgG fraction from healthy individuals. These observations infer that IgM autoantibodies are present in healthy individuals at levels higher than is reported normally, and at levels comparable with those found in relatives of SLE patients in which autoreactive antibodies are frequently reported, and their ability to bind ssDNA in whole serum is inhibited by IgG antibodies present within whole serum.

Keywords

SLE DNA antibody relative immunoglobulin fraction

Get full access to this article

View all access options for this article.

References

Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1983; 25: 1271-1277.

Ravirajan et al. Antigen binding diversity of human hybridoma autoantibodies derived from splenocytes of patients with SLE. Lupus 1992; 1: 167-174.

Longhurst C. , Watts R. , Isenberg DA The origin of natural autoantibodies. In: Shoenfeld Y , Isenberg DA (eds). Natural Autoantibodies-Their physiological role and regulatory significance . CRC press, Boca Raton, 1993, pp 205-235.

Schroeder HW , Hillson JL , Perlmutter RW Early restriction of the human antibody repertoire . Science 1987 ; 238: 791-793.

Lippman SM , Arnett FC , Conley CL Genetic factors predisposing to autoimmune diseases -autoimmune hemolytic anemia, chronic thrombocytopenic purpura and systemic lupus erythematosus . Am J Med 1982; 73: 827-840.

Wolfe F. , Kleinheksel SM , Khan MA Prevalence of familial occurrence in patients with rheumatoid arthritis. Br J Rheumatol 1988; 27 (Suppl. II): 150-152.

Fritzler MJ , Pauls JP , Kinsella TD , Bowen TJ Antinuclear, anti-cytoplasmic and anti-Sjogren's syndrome antigen A (SSA/Ro) antibodies in females blood donors. Clin Immunol Immunopathol 1985; 36: 120-128.

Adib M. , Radimbeau J. , Avrameas S. , Ternynck T. IgG autoantibody activity in normal mouse serum is controlled by IgM . J Immunol 1990; 145: 3807-3813.

Shields JG , Turner MW The importance of antibody quality in sandwich ELISA systems: evaluation of selected commercial reagents. J Immunol Methods 1986; 77: 314-318.

10.

Dudeney C. et al. A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members . Ann Rheum Dis 1986; 45: 502-507.

11.

Devey ME , Taylor J. , Steward MW Measurement of antigen-antibody complexes in mouse sera by conglutinin, C1q and rheumatoid factor solid phase binding assays. J Immunol Methods 1980; 34: 191-203.

12.

Devey ME et al. Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus. J Autoimmunity 1988; 1: 483-484.

13.

Isenberg DA et al. Measurement of anti-DNA antibodies: a reappraisal using five different methods. Ann Rheum Dis 1987; 46: 448-456.

14.

Steward MW , Hay FC Changes in immunoglobulin class and subclass of anti-DNA antibodies with increasing age in NWB/W F1 hybrid mice. Clin Exp Immunol 1976; 26: 363-370.

15.

Okamura M. et al. Significance of enzyme linked immunosorbent assay (ELISA) for antibodies to double stranded and single stranded DNA in patients with lupus nephritis: correlation with severity of renal histology. Ann Rheum Dis 1993; 52: 14-20.

16.

Kra-Oz Z. , Lorber M. , Shoenfeld Y. , Scharff B. Inhibitor(s) of natural anti-cardiolipin autoantibodies. Clin Exp Immunol 1993; 93: 265-268.

17.

Shoenfeld Y. et al. Polyspecificity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med 1983; 308: 414-420.

18.

Cairns E. , Block J. , Bell DA Anti-DNA autoantibody producing hybridomas of normal human lymphoid cell origin . J Clin Invest 1984; 74: 880-887.

19.

Lippman SM et al. Genetic factors predisposing to autoimmune diseases. Am J Med 1982; 73: 827-840.

20.

Revielle JD et al. Familial systemic lupus erythematosus: immunogenetic studies in eight families. Medicine 1983; 62: 21-35.

21.

Isenberg DA et al. Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives. Arthritis Rheum 1985; 28: 999-1007.

22.

LePage S. et al. Relation between lymphocytotoxic antibodies, anti-DNA antibodies, and a common anti-DNA antibody idiotype PR4 in patients with systemic lupus erythematosus, their relatives and spouses. Clin Exp Immunol 1989; 77: 314-318.

23.

Shoenfeld Y. et al. Detection of antibodies to total histones and their subfractions in systemic lupus erythematosus patients and their symptomatic relatives. Arthritis Rheum 1987 ; 30: 169-175.

24.

Miles S. , Isenberg DA A review of serological abnormalities in relatives of SLE patients . Lupus 1993; 2: 145-150.

25.

Zouali M. , Eyquem A. Expression of anti-idiotypic clones against auto-anti-DNA antibodies in normal individuals. Cell Immunol 1983; 76: 137-147.

26.

Avrameas S. , Dighiero G. , Lymberi P. , Guilbert B. Studies on natural antibodies and autoantibodies . Ann Immunol 1983; 134: 103-113.

27.

Cohen IR , Cooke A. Natural autoantibodies might prevent autoimmune disease. Immunol Today 1986; 7: 363-364.

28.

Halpern R. , Schiffenbauer J. , Solomon G. , Diamond B. Detection of masked anti-DNA antibodies in lupus sera by a monoclonal anti-idiotype . J Immunol 1984; 133: 1852-1856.

29.

Polanec J. , Seppala I. , Rousseau S. , Hedman K. Evaluation of protein-denaturing immunoassays for avidity of immunoglobulin G to rubella virus. J Clin Lab Anal 1994; 8: 16-21.

30.

Geha RS Presence of auto-anti-idiotypic antibody during the normal human immune response to tetanus toxoid antigen. J Immunol 1982; 129: 139-144.