Lymphoproliferation and autoimmunity - are they connected in patients with primary immunodeficiencies?
MoRE2020 Fellow Ola Grimsholm, incoming mobility from Bambino Gesu Children's Hospital, Italy, to the University of Gothenburg
This proposal aims at finding new diagnostic tools and new therapeutic targets for lymphomas. Lymphomas are life threatening cancers with about 2000 new cases every year in Sweden with an overall 5 year survival rate ranging from 65-80%. Lymphomas represent the most common form of blood cancer and they are mostly of B lymphocyte origin. B lymphocytes are one of the cell types of the immune system and they produce antibodies that protects us from re-infections. They are very important for response to vaccinations. Because of the poor survival rates in lymphomas we are in urgent need of new therapies and ways to diagnose them at an earlier stage of the disease. Patients born with defects in their immune system are usually more prone to develop lymphomas than normal healthy individuals. Many lymphomas arise during an immune response where B lymphocytes undergo a maturation process. During this process there are enzymes that introduce point mutations into the antigen receptor of the B lymphocytes, but this can also cause mutations that underpin lymphoma development. Here, we will sequence the DNA from patients with immunodeficiencies to dissect genes that might lead to lymphoma development. I expect that the results from this project will uncover genes important for lymphoma development and in the future this can be used to develop new diagnostic tools. Beyond the scientific interest, this project provides excellent training opportunities that have the purpose to advance my skills and boost my career prospects with the long term goal to become an independent group leader. Furthermore, the results will have a direct impact on the research and innovation milieu in Västra Götaland region since new diagnostic tools for cancer are crucial and very beneficial for our society.
Collaborating end-user: Sahlgrenska University Hospital
Summary of Project Results
We still know very little about how the immune system is regulated on a genetic level in humans. Most of our knowledge so far comes from studies on mouse models but the significance of such results on the human immune system is sometimes hard to evaluate. This project aimed at evaluating the genetic background in patients with primary antibody deficiencies. We have found that there is an imbalance of important transcription factors inside the B lymphocytes from this patient group. We have also sequenced the DNA of all patients in order to connect what we see on the cellular level with the genetic background. This has been a collaboration between several milieus including University of Gothenburg, Karolinska institute, Bambino Gesu Children Hospital and the end user Sahlgrenska University Hospital. The project will lead to at least two scientific publications that are planned for submission during 2020. In the next step, we want to develop a method based on the results on the B lymphocytes from the patients where we hope that we can predict which patients that has a higer risk to develop more severe symptoms over time. On a personal level this MoRE2020 fellowship has allowed me to develop my own research group and the establishment will take place somewhere in Europe in the upcoming years.