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Immunomodulation by IVIg: towards an optimized therapy

Wednesday 21 August 2013

Intravenous immunoglobulin (IVIg) is a pharmaceutical preparations of human IgG molecules derived from thousands of healthy donors. IVIg is used as supplementary therapy in patients suffering from immune deficiencies to restore IgG levels and recover antibody-mediated responses. In contrast, higher dose of IVIg is effective in inhibiting inflammatory responses and has shown to be successful in treatment of auto-immune diseases and suppressing graft rejection, e.g. after liver transplantation. Hence, IVIg can, paradoxically, restore either pro-inflammatory responses or induce anti-inflammatory activity, depending on the infused dose. In the past decades many cellular components of the immune system have shown to be involved in the anti-inflammatory activity of IVIg. However, how IVIg modulates these immune cells at a molecular level is far from elucidated. Identification of IVIg-binding molecules on the cell surface of these immune cells may lead to targeted IVIg therapy in which pro- and anti-inflammatory components within IVIg can be separated or, alternatively, enable the generation of more effective treatment modalities.

In our lab, we are currently focusing on the immunomodulatory effect of IVIg on three key regulatory cell types of the immune system: dendritic cells, macrophages and regulatory T cells. By studying these cell types in vivo and in vitro, we are uncovering how IVIg functionally affects these cells. Moreover, we have identified several cell surface proteins on human macrophages that may be able to bind IVIg. In the current project, a number of these putative IVIg binding candidates will be studied. You will ascertain whether IVIg truly binds to (one of) these candidates and assess the functional implications upon binding.

Techniques involved for this project include amongst others: flowcytometry, cell purification, cell culture, ELISA, Western Blot, PCR, sequencing and cloning. You will be closely supervised on and off the lab by an experienced postdoc.

We are looking for a motivated medical student who likes a challenge. This project provide an excellent opportunity to get in touch with basic immunological research. You will be coached throughout the project. Emphasis will be on personal development and on acquiring research skills both on and off the lab. With good quality results, you will be included as an author on a publication.

Rogier van Gent: r.vangent@erasmusmc.nl
Jaap Kwekkeboom j.kwekkeboom@erasmusmc.nl

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