Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression.
Mice with experimental anti-phospholipid syndrome (APS), induced by active immunization with a human anti-cardiolipin MoAb (H-3), were treated with mouse anti-idiotypic MoAb (anti-H3, named S2.9) and with an irrelevant anti-idiotype. The immunized mice produced high titres of mouse anti-cardiolipin antibodies along with clinical manifestations of experimental APS: prolonged activated partial thromboplastin time (aPTT), thrombocytopenia and high rate of fetal loss. Treatment with the specific anti-Id (S2.9) as a whole molecule or F(ab)2 fraction, resulted in a decrease in serum levels of the anti-cardiolipin antibodies, rise in platelet count, shortened aPTT and reduced rate of fetal loss. The anti-Id effect was associated with a rise in the number of IL-2 and interferon-gamma (IFN-gamma)-secreting cells (Th1) and reduction in IL-4- and IL-6-secreting cells (Th2). The beneficial effect of the anti-Id treatment in mice with experimental APS induced by active immunization with an idiotype further supports the idiotypic aetiology of experimental APS and points to the role of Th1 cytokines in suppression of its manifestations.
Research Unit of Autoimmune Diseases, Department of Medicine B, Sheba Medical Centre, Tel Hashomer and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
I
I
Krause
M
M
Blank
Y
Y
Levi
T
T
Koike
V
V
Barak
Y
Y
Shoenfeld
D000026:Abortion, Habitual / Q000209:etiology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000628:therapy*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D010314:Partial Thromboplastin Time; D011247:Pregnancy; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D013921:Thrombocytopenia / Q000209:etiology
D000888:Antibodies, Anti-Idiotypic; D017153:Antibodies, Anticardiolipin; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4; D007371:Interferon-gamma