Researchers track down rare immunodeficiency genes
Docent Mikko Seppänen’s clinical immunology research group studies rare and congenital immune disorders which are either new or have accumulated in Finland. They are usually caused by a single mutation in the genome. The development of targeted treatment would significantly change the patients’ well-being.
Mikko Seppänen’s research group, which has been active for six years, includes experts in the genetics of primary immunodeficiency and clinical treatment. The group cooperates closely with research groups in rheumatology, hematology, gastroenterology and dermatology and with university hospitals, European research groups, cellular biologists, researchers in translational medicine and laboratory immunologists.
– We study immunodeficiency, autoinflammation and autoimmune diseases. There is a lot to study, since according to estimates, there are still thousands of new immunodeficiency genes and their phenotypes which have not been described. It has been found that Finland has the second-highest prevalence of primary immunodeficiencies in the world, but little research has been made in the field, Mikko Seppänen states.
The research patients in Seppänen’s group have been previously examined by means such as clinical exome sequencing, but these studies did not discover mutations explaining well-known immunodeficiency genes. The group continues to analyse the results or perform a genome sequencing procedure, which will lead to the discovery of the candidate gene.
Studying the malfunction in the gene affecting immunity will help understand the human defence mechanism and its malfunctions in terms of more common diseases as well. For most diseases, it will also be possible to detect a change in the inflammation response.
New hope for the treatment of rare diseases
Seppänen’s group has been involved in the description of new diseases, phenotypes and the diseases in the Finnish disease heritage. New monogenic immunity disorders include TOM1 and STAT3 mutation, HYOU1 deficiency, the new phenotypes include CEBPE, NFKB1 and ADA2 mutations, SLFNL1 mutation and SLFN11, SLFN12 and SLFN13 copy-number variations. The new diseases in the Finnish disease heritage include AICDA founder mutation.
The group will continue to intensively study new hereditary immunodeficiencies. The researchers have discovered that the world’s most common serious immunodeficiency, chronic venous insufficiency (CVI), is more than twice as prevalent in Finns than in the rest of the world’s population.
– We are working intensively to establish the cause of this disease. In addition, our short-term objective is to publish information on two other immunodeficiencies. We will also describe in more detail the diseases caused by NFKB1, TMEM173 and TNFAIP3 mutations. We will naturally continue to study several new candidate genes in conjunction with the other groups.
Each new monogenic disease which results in more effective targeted treatment of patients brings great satisfaction to the research group.
Helsinki University Hospital, Rare Diseases Center