Primary Immunodeficiencies (PIDs) encompass several groups of diseases resulting from primary impairment in one or both arms of the immune system: the innate immune system (i.e. the part of the immune system that lacks immunologic memory and occurs to the same extent however many times the infectious agent is encountered) and/or adaptive system defenses (i.e. the part of the immune system that has immunologic memory that results in stronger and faster attacks each time the infectious agent is encountered).

Innate system impairment may result from aberrant receptors signaling (1,2), lack of innate system proteins (e.g. complement deficiencies)(3,4), or impairment of innate system cells(5-7). Adaptive system impairment may result in severe combined immunodeficiency(8-12), signaling defects resulting in combined immunodeficiencies (CID),(13-15) DNA repair defects (16), immune-osseous dysplasias(17,18), thymic disorders(19,20), aberrant IgE production disorders(21-23) and abnormalities of apoptosis(24,25) and immune-regulation(26-31) and B cell- immunodeficiencies(32,33).

These immune impairments further contribute to increased susceptibility to infections autoimmunity, autoinflammatory syndromes and malignancy(27,34,35)

Diagnosis of PIDs is based on the corroboration of clinical history with appropriate functional and genetic tests. Given that the underlying genetic basis is known for many forms of immunodeficiency, diagnosis of index cases as well as family members and prenatal diagnosis has been facilitated(36).

Current treatment of PIDs is based on symptomatic treatment and curative treatment. Symptomatic treatment includes treatment of infectious and immunodyregulatory complications such as autoimmunity and malignancy (34,37,38). Curative treatment includes hematopoietic stem cell transplantation(39-41) or thymic transplantation(42) and gene therapy(43-46).

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