Immunodeficiency . Inborn Errors of Immunity . Immune Dysregulation . Autoimmunity Mutation . Personalized Therapy 


Primary Immunodeficiency

Primary immunodeficiencies (PID), also known as inborn errors of immunity (IEI), are a rapidly evolving group of genetically determined human diseases associated with susceptibility to infection, autoimmunity/autoinflammation and/or lymphoproliferation. To date more than 450 different PID entities have been elucidated. The main current basic immunology focus of the research lab is to characterise the role of a yet poorly studied transcription factor in the generation and maintenance of human memory T lymphocytes. This is done by analysing functional consequences of T cell intrinsic over- expression vs. knock-out of the transcription factor complemented by a detailed clinical immunology assessment of patients carrying homozygous loss of function mutations in the gene encoding the transcription factor. 
The aim is to molecularly define a non-redundant role for this transcription factor in the generation of human T cell memory and to characterise drugable targets to potentially restore immunity in patients carrying loss of function mutations in the gene encoding this transcription factor. 

Connection to Clinical Practice

Mike Recher; Christoph Hess Immunodeficiency Clinic, Medical Outpatient Unit, University Hospital Basel

Molecular dissection and personalised treatment of patients with primary immunodeficiency 

Patients with suspected immunodeficiency or immune dysregulation are clinically evaluated in the Immunodeficiency Clinic of the Medical Outpatient Unit of the Basel University Hospital. Patients are treated with immunoglobulin supplementation and, if available, specific immuno-active compounds. Since 2015, patients with the diagnosis of primary (genetically determined) immunodeficiency are included into a prospective research cohort. Following informed consent, a standardised documentation of the physical status of the patient is combined with analysis of clinically validated and/or research based immunological lab data and next generation immune-gene sequencing. This allows us to prospectively study the disease course but also to determine the molecular mechanism of disease and at best to treat the patients in a targeted, personalised manner.
Currently, more than 225 patients have been included into the prospective cohort and selected patients are further molecularly characterised in the research lab. Novel disease causing immune gene variants  have been identified in CTLA-4, SP110, SDHA, SAMHD1, Ligase 4 and many others. Novel targeted personalised treatment strategies have been or are currently clinically evaluated in patients with disease causing mutations in CTLA-4, SDHA, POLA1, SAM-HD1 and others.