Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression

Abstract

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.

Fig. 1

Kinetics of mouse anti-cardiolipin titres in the sera of mice with experimental anti-phospholipid syndrome (APS) following treatment with a specific (S2.9) and irrelevant mouse anti-SA-1 (MαSA-1) anti-idiotypic antibodies, whole molecule (WM), F(ab)₂ and Fc fragments (n = 5).

Fig. 2

Representative profile of cytokine spot-forming cells 1 month after boost injection (n = 5 for each group). Data are expressed as mean ± s.d. for each mouse.

Fig. 3

The number of IL-4- and IL-6-secreting splenocytes from mice with experimental anti-phospholipid syndrome (APS) 8 weeks after treatment with specific (S2.9) and irrelevant mouse anti-SA-1 (MαSA-1) anti-idiotypic antibodies, whole molecule (WM), F(ab)₂ and Fc fragments (n = 5).

Fig. 4

The number of IL-2- and IFN-γ-secreting splenocytes in mice with experimental anti-phospholipid syndrome (APS) following treatment with specific (S2.9) anti-idiotypic antibody and irrelevant mouse anti-SA-1 (MαSA-1) anti-idiotypic antibodies, whole molecule (WM), F(ab)₂ and Fc fragments.

Fig. 5

The concentrations of Th1/Th2 cytokines in the sera of anti-phospholipid syndrome (APS) mice, following treatment with specific (S2.9) and irrelevant mouse anti-SA-1 (MαSA-1) anti-idiotypic antibodies, whole molecule (WM), F(ab)₂ and Fc fragments (n = 10).

Fig. 6

Anti-cardiolipin (CL), anti-phosphatidylserine (PS) and anti-ssDNA antibody-forming cells (AFC) in mice with experimental anti-phospholipid syndrome (APS) following treatment with specific (S2.9) and irrelevant mouse anti-SA-1 (MαSA-1) anti-idiotypic antibodies, whole molecule (WM), F(ab)₂ and Fc fragments.