Immunology

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Recurrent, severe, persistent or unusual infections, including opportunistic pathogens or
• Immune dysregulation, such as autoimmunity, autoinflammation, lymphoproliferation or malignancy
• A positive family history of primary immunodeficiency
• Patients meeting any of the ten warning signs of primary immunodeficiency or meeting ESID clinical working definitions for a primary immunodeficiency, such as antibody deficiency

Testing is typically requested by clinical immunologists, paediatricians, haematologists and infectious-disease physicians.

Genetic testing is considered when an inborn error of immunity is suspected on clinical or family-history grounds, and it supports clinical decision making. For example, in families with suspected inborn errors of immunity, comprehensive genetic evaluation established a molecular diagnosis in 60%.

• A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and condition.
• A variant of uncertain significance (VUS) cannot currently be classified as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates.
• In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.
• Each variant is classified according to .

When a pathogenic or likely pathogenic variant is identified, it establishes the molecular diagnosis and can guide management. Depending on the condition, this may inform treatment decisions, including eligibility for haematopoietic stem-cell transplantation or gene-targeted therapy. A confirmed germline variant also carries familial implications, and cascade or predictive testing can be offered to at-risk relatives.

is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country. Please to check out access in your region.