IVIG/SCIG Inhibits T-cell Activation.

[Ema]

Curious how inhibition of T cells would manifest in real life...would reduction of these cytokines be why high dose IVIG often helps with autoimmune disease?

Clin Immunol. 2015 May 14;160(2):123-132. doi: 10.1016/j.clim.2015.05.003. [Epub ahead of print]

Intravenous IgG (IVIG) and subcutaneous IgG (SCIG) preparations have comparable inhibitory effect on T cell activation, which is not dependent on IgG sialylation, monocytes or B cells.

Issekutz AC1, Rowter D2, Miescher S3, Käsermann F4.

Author information



Abstract

IVIG modulates T cell activation in vitro and inflammatory-autoimmune conditions in vivo. Sialylation of IgG, Fc receptor interactions, modulation of monocyte/macrophage/B cell functions have been implicated in IVIG effects. Subcutaneous IgG (SCIG) therapy is increasingly used for IgG replacement but whether these preparations share the effects of IVIG on T cell modulation is not documented.

We compared the potency of SCIG-Hizentra™ (20% IgG preparation) with IVIG-Privigen® (10% IgG) for T cell inhibition, and assessed the involvement of IgG sialylation, monocytes and B cells in this process. Human PBMCs or sorted cells were cultured 3-7days, and T cells were stimulated with immobilized anti-CD3 mAb or Candida antigen. Thymidine incorporation into DNA was quantitated and cytokines assayed by ELISA/Luminex® assay.

IVIG and SCIG both dose-dependently (1-20mg/ml) inhibited (up to >80%) T cell proliferation to anti-CD3 mAb. Response to Candidaalbicans was comparably inhibited by IVIG and SCIG by 50-80% at 10mg/ml with inhibition even at 3mg/ml (P<0.05). These effects were not affected by depletion of sialic acid containing IgG using neuraminidase treatment or lectin affinity chromatography. With anti-CD3 or Candida stimulation, IL-1β, IL-2, IL-5, IL-6, IL-13, GMCSF, TNF-α, interferon-γ (with anti-CD3) and IL-17 (with Candida) levels were suppressed by IVIG or SCIG, with no effect on IL-4, IL-10, IL-12, IL-15 or TGFβ. Monocytes or B cells were not required for IgG-induced suppression of proliferation, in fact depletion of monocytes potentiated the IgG-induced inhibition. Reconstitution with monocytes restored the original inhibitory effect.

These data show that IVIG (Privigen®) and SCIG (Hizentra™) have comparable inhibitory effects on T cell activation, which do not require sialylation of IgG. Inhibition is independent of monocytes or B cells. There is a potent suppression of multiple effector cytokines. Like IVIG, SCIG therapy is expected to show immunomodulatory activity.

Copyright © 2015 Elsevier Inc. All rights reserved.

 

[minkeygirl]

This also shows that SCIG is as effective as IVig so much fewer problems.

 

[Jonathan Edwards]

Curious how inhibition of T cells would manifest in real life...would reduction of these cytokines be why high dose IVIG often helps with autoimmune disease?

I may be wrong but I think this study is probably crazy.
They say they gave IVIG and SCIG to T cell sin vitro. But you cannot give immunoglobulin intravenously or subcutaneously to cells in a tissue culture dish so the results have nothing whatever to do with whether you give Ig IV or SC to a patient.

It is crazy isn't it? I find it hard to believe I am reading this.

Maybe they are comparing two different preparations of Ig - that happen to be marketed for different routes. But then all they are showing is that they are pretty much the same stuff. Again it tells you nothing whatever about the advantages or disadvantages of the way you give them to patients.

The other thing that is weird is that if there are no macrophage or B cells there then there seems to be no way that the T cells could tell that this is pooled' other people's Ig' rather than Ig from the person the T cells came from. So they are not even testing the effect of allogenous Ig (IVIG and SCIG can only work if it matters that they come from someone else), they are just looking at the effect of immunoglobulin on T cells. So, since everyone has their own immunoglobulin it would not seem they are measuring anything to do with IVIG or SCIG therapy at all.