Research study update: Isolation of natural human antibodies in blood
What was the question?
This project is an exciting search for the holy grail of anti-D donor research: identifying the “secret sauce” in a person’s immune response that makes them produce anti-D antibodies.
Lifeblood researchers are working with researchers led by Professor Ian Wicks at the Walter and Eliza Hall Institute of Medical Research (WEHI) to investigate the range of antibodies produced by our anti-D donors.
The ultimate goal is to create cells that will be able to grow in the lab and work as “anti-D factories”, which could meet the needs of expectant mums without the need to boost and bleed anti-D donors.
Why is it important?
Antibodies are naturally occurring molecules which can help protect you against infection and disease. They’re produced by B-cells in your immune system.
Anti-D is an important antibody product that’s used to help prevent a devastating disease, known as Hemolytic Disease of the Fetus and Newborn (HDFN). This disease occurs when a woman with RhD negative blood develops antibodies which can attack the blood of her unborn child if the child is RhD positive. It can lead to miscarriage or stillbirth, as well as other complications.
However, if given early enough to the mother, these same antibodies (which we call anti-D), can protect the baby by ‘mopping up’ the baby’s red blood cells before they stimulate her B cells to form antibodies against RhD.
Currently, we depend on the generosity of a small number of dedicated donors to supply the anti-D that’s required for all RhD negative pregnant women in Australia to help prevent this deadly disease.
What did we do?
Lifeblood recruited 30 current anti-D donors to the study, who provided a blood sample to send to WEHI in Melbourne for the study.
For the researchers to be able to isolate functioning B cells, the sample collection needed to be carefully timed and co-ordinated between the anti-D team, donor centres, our manufacturing staff and WEHI.
We’ve reached our target of 30 samples to start this important research.
What did we find out?
Our collaborators at WEHI are teasing out the detail of the anti-D response.
When each sample arrives, they isolate the plasma fraction and a group of cells known as peripheral blood mononuclear cells (PBMCs). This group of cells includes the B cells from the immune system. Some parts of each sample are specially frozen and stored for later use.
So far, our collaborators at WEHI have:
- isolated single B cells from the PBMCs and sequenced the genes that code for antibodies, including anti-D antibodies.
- separated the collection of antibodies that bind to RhD positive red cells from the plasma fraction. They’re now using a technique known as proteomics to work out the details of the antibodies’ amino acid sequences to see what they have in common.
- developed ways to test how the antibodies work by applying them to cells in the laboratory and measuring if the antibodies kill the cells directly, or stimulate other immunes cells to “eat” them, or a combination.
- established a way to watch live cells under a microscope to observe how RhD and red cells interact with immune defence cells, and how the interaction changes when anti-D antibodies are present.
Professor Wicks has been awarded a Normal Beischer Innovation Grant to support this research.
What’s happening next?
Professor Ian Wicks and his team will continue working on the samples we’ve provided so far, and use the new tests they’ve developed to understand how anti-D affects the immune system and which antibody characteristics are needed to make it work.
We hope that the knowledge that comes from this study can improve the availability of anti-D for pregnant women not just in Australia, but around the world.