Study sheds light on why immunodeficiency affects only one identical twin
Analysis of the identical twin participants found that not only did the sibling with CVID have fewer B cells, but that B cell defects resulted in epigenetic problems with DNA methylation, chromatin accessibility and transcriptional defects in memory B cells themselves. In addition, researchers found massive defects in the cell-to-cell communication required for the immune system to function normally.
Dr Javier Rodríguez-Ubreva, a first author of the study from the Josep Carreras Leukaemia Research Institute, said: “The human immune system is not a static entity and communication between immune cells is vital for it to work effectively. We can see in healthy individuals how cells talk to each other and from there identify where communication breaks down in individuals with common variable immunodeficiency (CVID). In the immune system this cell-to-cell communication is critical to define the ability of B cells to mature and produce antibodies.”
The researchers compared the epigenetic changes and cell-to-cell communication problems found in the twin suffering from CVID against a wider CVID cohort and found that the problems were the same, providing a solid model for characterising the disease. The challenge now will be to use these insights to develop new treatments.
Dr Esteban Ballestar, a senior author of the study from the Josep Carreras Leukaemia Research Institute, said: “This is the first of many studies that will look at common variable immunodeficiency (CVID) and other primary immunodeficiencies in the attempt to identify new therapies for treating these disorders. We already have viable options, such as immunoglobulin replacement therapy, which I would hope can be adapted to address the specific B cell defects that we have identified here.”
As well as immunoglobulin replacement therapy, epigenetic drugs can also be used to treat immune disorders and the findings of this study highlight a number of biological pathways worthy of further investigation for new drug targets.
Dr Roser Vento-Tormo, a senior author of the study from the Wellcome Sanger Institute, said: “This is the first cell atlas to categorise common variable primary immunodeficiencies and will be a valuable contribution to the Human Cell Atlas initiative to map every cell type in the human body. What this study in particular shows is how quickly cell atlas data can be applied to better understand specific health challenges and open up new avenues of treatment.”