Primary Immunodeficiency Disorders

Disorders in which part of the body's immune system is missing or does not function normally

Aetiology

  • PIDs are due to genetic causes - may result from a single genetic defect, but most are multifactorial

Pathophysiology

PIDs of the innate immune system

Severe congenital neutropenia
  • Low neutrophils
  • SCN Type I is the commonest form - autosomal dominant in the gene which codes for neutrophil elastase, causing a defect in neutrophil development
Leukocyte adhesion deficiency
  • Caused by defect in the CD18 integrin gene - neutrophils cannot recognise markers expressed on endothelial cells, which results in failure of neutrophil adhesions and migration
Chronic granulomatous disease
  • Inability of macrophages to generate oxygen/nitrogen free radicals (ROS/RNS) → impaired killing of intracellular microorganisms → excessive inflammation → granuloma

PIDs of the adaptive immune system

Severe combined immunodeficiency
  • Failure of production of lymphocytes
X-linked SCID
  • Mutation of IL-2 receptor → inability to respond to cytokines → failure of T and NK cell development, production of immature B cells
Bruton’s X-linked hypogammaglobulinaemia
  • Mutations in BTK gene - essential for B cell development
Defects in the IL-12: IFN𝛾 network
  • IL-12: IFN𝛾 network defends against intracellular mycobacteria
Transient hypogammaglobinemia of infancy
notion image

Clinical presentation

  • Weight loss
  • Eczema
  • Chronic diarrhoea
  • Mouth ulceration
  • SPUR infections - serious, persistent, unusual, recurrent

Investigations

  • Basic tests include FBC and immunoglobin levels
  • Other tests are performed depending on the suspected disorder

Management

  • IV Ig
  • Aggressive management of infection - antibiotics, antifungals
  • Definitive therapy - stem cell transplant, gene therapy, recombinant G-CSF for SCN