Severe combined immunodeficiency

Background

Epidemiology

• Most common form of severe primary immunodeficiency

Pathophysiology

• No or almost no T-cells, and any that exist do not work properly
• Many genetic abnormalities can lead to this condition, and may cause related defects in B and NK cell lines
• However, given that T-cells are required for B-cell function, all SCID patients are functionally B-cell deficient

Diagnosis

• Usually diagnosed at birth with newborn screen containing a TREC (T-cell receptor excision circles) assay
• In adulthood, diagnosis is based on flow cytometry to T cell count, and T cell response to mitogens (see Definition, below)

Definition

• T-cell count <300 cells/μL and no T-cell response to mitogens (<10% compared to controls)
• Hypomorphic SCID is less severe, with a normal number of T-cells, but with T-cell function <30% compare to controls

Management

• Initially treated supportively with management of infections and replacement of immunoglomubins
• Protective isolation in hospital with positive pressure rooms
• Antibiotic and antifungal prophylaxis to reduce frequency and severity of infections
  • Commonly-used antibiotics include sulfisoxazole, amoxicillin, trimethoprim-sulfamethoxazole, or azithromycin
• Avoid live-attenuated vaccines, but can continue to give killed or subunit vaccines (though they may not mount much response)
• Definitive treatment is hematopoietic stem cell transplantation, ideally from HLA-identical sibling
• Gene therapy is an area of active research

Prognosis

• Uniformly fatal in childhood unless treated