Differential Diagnostic in Cellular Immunodeficiencies

More than 400 monogenic Inborn Errors of Immunity (IEI) are known, and the number is increasing rapidly. Their diagnosis might be considered as definitive by the identification of the underlying molecular defect and of a known monogenic pathological variant in a patient with a given clinical and immunological phenotype. Phenotype of IEI patients includes susceptibility to bacterial, fungal, and viral infection diseases and also auto-inflammatory and autoimmune disorders and increased incidence of malignancies. Despite the advances of genetic diagnostic technologies, many patients with clinical and immunological phenotypes compatible with a possible IEI diagnosis still lack a definitive genetic diagnosis or are misdiagnosed. Early diagnosis on a primary immunodeficiency condition might help to prevent long-term organ damages. This can result in diagnostic delay and worsen prognosis. Therefore, a differential clinical, immunological, and genetic diagnostic workup is required for the majority of IEI patients, knowing that phenotype varies also within the same clinical entity and it might change with time.