DNA antibody class, subclass, and complement fixation in systemic lupus erythematosus with and without nephritis

doi:10.1016/0090-1229(78)90158-7

Clinical Immunology and Immunopathology

Volume 10, Issue 4, August 1978, Pages 459-467

Clinical Immunology ...

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Abstract

Using a recently described indirect immunofluorescence technique which employs the kinetoplast of a nonpathogenic hemoflagellate, Crithidia luciliae, as a native DNA substrate, we have compared the complement-fixing, Ig class, and subclass properties of anti-native DNA antibodies in sera from systemic lupus erythematosus patients with and without nephritis. With this simple technique we have found that complement-fixing native DNA antibodies are more specific for lupus nephritis than are non-complement-fixing native DNA antibodies. We have also shown that nephritis patients usually have native DNA antibodies in all three major immunoglobulin classes and more frequently have the IgG native DNA antibody subclasses that fix complement, IgG1 and IgG3. These findings support the hypothesis that in systemic lupus erythematosus the biological properties of the antibodies produced as well as the intensity of the DNA antibody response are important determinants in the nephrotoxicity of immune complexes composed of native DNA and its antibody.

References (33)

G. Stingl et al.
Clin. Immunol. Immunopathol.
(1976)
R.A. Nelson et al.
Immunochemistry
(1966)
E.M. Puritz et al.
Clin. Immunol. Immunopathol.
(1973)
E.M. Tan et al.
J. Clin. Invest.
(1966)
D. Koffler et al.
J. Exp. Med.
(1967)
C. Krishnan et al.
J. Clin. Invest.
(1967)
P.H. Schur et al.
N. Engl. J. Med.
(1968)
G.A. Andres et al.
J. Clin. Invest.
(1970)
D. Koffler et al.
J. Exp. Med.
(1971)
D. Koffler et al.
J. Exp. Med.
(1971)

D. Koffler et al.

J. Clin. Invest.

(1973)

D. Koffler et al.

Amer. J. Pathol.

(1974)

E.J. Bardana et al.

Amer. J. Med.

(1975)

J.B. Winfield et al.

J. Clin. Invest.

(1975)

J.B. Winfield et al.

J. Clin. Invest.

(1977)

N.F. Rothfield et al.

J. Clin. Invest.

(1967)

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¹: Research Fellow in Internal Medicine.

²: Recipient of USPHS Research Career Development Award No. 00278.

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DNA antibody class, subclass, and complement fixation in systemic lupus erythematosus with and without nephritis

Abstract

Clin. Immunol. Immunopathol.

Immunochemistry

Clin. Immunol. Immunopathol.

J. Clin. Invest.

J. Exp. Med.

J. Clin. Invest.

N. Engl. J. Med.

J. Clin. Invest.

J. Exp. Med.

J. Exp. Med.

J. Clin. Invest.

Amer. J. Pathol.

Amer. J. Med.

J. Clin. Invest.

J. Clin. Invest.

J. Clin. Invest.