The diverse pathogenic potential of anti-DNA antibodies from various sources to induce experimental systemic lupus erythematosus.
It has previously been shown that immunization with pathogenic anti-DNA idiotypes (Ids; e.g. 16/6 Id) leads to the induction of experimental system lupus erythematosus (SLF) in naive mice. The disease is characterized by serological (e.g. anti-double-strand DNA), clinical (elevation of erythrocyte sedimentation rate, leukopenia and proteinuria) and histological (immune complex deposition in kidneys) parameters. To determine whether the 16/6 Id carrying anti-DNA antibodies has unique pathogenic ability, in the current study we have employed diverse sources of anti-DNA antibodies to induce experimental SLE. An IgM anti-DNA antibody lacking the 16/6 Id was able to induce the production of the serological markers of experimental SLE, but not the clinico-histological findings. Furthermore, an IgA anti-DNA (16/6 Id derived from the serum of a patient with celiac disease was very effective in inducing the whole presentation of experimental SLE. Other anti-DNA antibodies failed to induce the autoimmune condition. Combined with our previous experience, the current study points to the diverse potential of various anti-DNA antibodies to induce SLE. The 16/6 Id is only one of a list of the potent pathogenic anti-DNA Ids. These facts may explain in part the diversity of clinical presentations of SLE, including asymptomatic subjects who carry high serum titers of anti-DNA antibodies.
Swissa
M
M
Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
Lerner
A
A
Sasaki
T
T
Sela
E
E
Blank
M
M
Shoenfeld
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000145:classification / Q000276:immunology* / Q000633:toxicity*; D004247:DNA / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced*; D051379:Mice; D008807:Mice, Inbred BALB C
D000974:Antibodies, Antinuclear; D004247:DNA