New methods to study antibody deficiencies
Resident in pediatrics, Juha Grönholm MD, PhD, studies primary immunodeficiencies. The study utilizes exome and genome sequencing to identify gene mutations causing new immunodeficiency syndromes in material collected on Finnish patients.
These diseases are rare, but their number is exceptionally high in Finland. In his study, Grönholm focuses on the congenital defects related to the acquired immunity. The studies will also provide new information on the function of the human immune system.
In 2016, Grönholm returned to Finland after a three-year postdoc period at the National Institutes of Health in the United States. There, in collaboration with British and American researchers, he discovered the primary immunodeficiency syndrome caused by BACH2 gene mutations.
Grönholm is currently involved in Docent Mikko Seppänen’s projects at the University of Helsinki. The research is in its early stages, but there are already several potential disease gene candidates for further studies. This will lead to the discovery of novel primary immunodeficiency syndromes and potentially even entirely new genes affecting the human defence system.
The study requires competencies in both immunology and cellular and molecular biology. During his postdoc years, Grönholm has obtained particular experience in flow cytometry and functional assays with T and B lymphocytes.
– With Mikko Seppänen’s group and, among others, with the laboratories of Professor Juha Kere and Docent Markku Varjosalo, we will examine what types of changes the discovered gene mutations will cause in the function of the proteins coded by the respective genes. Results from the in vitro experiments will then indicate whether the mutation causes the changes detected in patients on a cellular level and their symptoms, Juha Grönholm explains.
Currently, most of the studied patients are adults, but in the future, the aim is to concentrate more on pediatric patients.
Although it is not yet possible to correct congenital genetic mutations, discovering the cause of the disease is important to patients.
– When we are familiar with the exact molecular mechanism of the disease, we are able to develop targeted therapies. Knowledge of the inheritance of the disease is also useful to families planning to have children. The information allows for the early screening of the disease-causing gene variant and in children, and for instance, the early-onset of the intravenous immunoglobulin therapy or other potential treatment for affected individuals, Juha Grönholm says.
The objective is to increase the number of researchers within his personal research group and to transform it into an independent research group in the future.
Helsinki University Hospital Children and Adolescents