The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/7/29/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 1, July 1, 1998 29-38

Articles

Immunization with a Peptide Surrogate for Double-stranded DNA (dsDNA) Induces Autoantibody Production and Renal Immunoglobulin Deposition

Chaim Putterman* and Betty Diamond*,{ddagger}

From the * Division of Rheumatology, Department of Medicine, and the {ddagger} Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461

Anti–double-stranded DNA (dsDNA) antibodies are the serologic abnormality characteristically associated with systemic lupus erythematosus (SLE) and may play an important role in disease pathogenesis. Although the anti-dsDNA antibodies present in SLE are indicative of an antigen-driven response, the antigen has not been conclusively identified.

By screening a phage peptide display library, we demonstrated previously that the decapeptide DWEYSVWLSN is specifically bound by the pathogenic murine IgG2b anti-dsDNA antibody R4A. To investigate the possibility that a protein antigen might trigger lupus-like autoimmunity, we immunized BALB/c mice with DWEYSVWLSN in adjuvant. Mice developed significant titers of IgG anti-dsDNA antibodies 2–3 wk after the initial immunization. Immunized mice also developed antibodies against some other lupus autoantigens, and immunoglobulin deposition was present in renal glomeruli at 49 d. Although an immune response to peptide and dsDNA was evident in BALB/c mice, there was little response in other inbred strains.

This study demonstrates that lupus-like anti-dsDNA reactivity can be generated in nonautoimmune mice by immunization with a peptide antigen. Peptide-induced autoimmunity may prove useful in understanding the spreading of antigenic specificities targeted in SLE. However, most importantly, the demonstration that a peptide antigen can initiate a SLE-like immune response opens a new chapter on the potential antigenic stimuli that might trigger SLE.

Key Words: systemic lupus erythematosus • anti-DNA • peptide library • autoantibodies • inbred strains

Address correspondence to Betty Diamond, Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461. Phone: 718-430-4081; Fax 718-430-8711; E-mail: diamond{at}aecom.yu.edu

Abbreviations used: ANA, antinuclear antibody; dsDNA, double-stranded DNA; GXM, glucoronoxylomannan; MAP, multiple antigenic peptide; RNP, ribonucleoprotein.


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