Progression of lupus-like disease drives the appearance of complement-activating IgG antibodies in MRL/lpr mice.
OBJECTIVE
Nucleic acids are known to induce complement activation, which results in the masking and removal of apoptotic cells exposing nuclear components. Dysregulation of these events is characteristic of SLE, a systemic autoimmune disease characterized by the appearance of ANAs. In this study, we aimed to investigate the relationship between development of ANAs and their effect on complement activation by nucleic acids.


METHODS
We used protein array technology to characterize complement activation by murine mAbs and polyclonal antibodies against various forms of nucleic acid. Serum samples from MRL/lpr mice were collected, starting before the onset of the disease till 6 months of age. Binding of IgG and its subclasses to dsDNA, ssDNA, RNA, plasmid DNA and nucleosome complexes was determined, along with C3 fixation.


RESULTS
We show that complement C3 binding to various forms of nucleic acid that serve as targets in lupus is absent in normal serum. The addition of dsDNA-specific mAbs to normal serum results in the deposition of complement C3 to nucleic acids. In MRL/lpr mice, IgG antibodies against various nuclear antigens appear with ageing and disease progression. C3 binding to the antigens is somewhat delayed and suggests that accumulation or maturation of pathogenic antibodies is required for inducing C3 binding to ICs containing nucleic acids.


CONCLUSIONS
C3 deposition on nuclear antigens, therefore, reflects the state of disease progression in this murine model of SLE.
Papp
Krisztián
K
Department of Immunology, Eo¨ tvo¨ s Lora´ nd University, Budapest, Hungary.
Végh
Péter
P
Tchorbanov
Andrey
A
Vassilev
Tchavdar
T
Erdei
Anna
A
Prechl
József
J
D000818:Animals; D000906:Antibodies; D000974:Antibodies, Antinuclear / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D018450:Disease Progression; D007074:Immunoglobulin G / Q000276:immunology*; D008178:Lupus Erythematosus, Cutaneous / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D023421:Models, Animal
D000906:Antibodies; D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D003165:Complement System Proteins