Table 1

Clinical approach to human primary immunodeficiencies

Clinical presentationExamples of common causative PIDsPreliminary investigationsSpecialised investigationsTherapeutic options (with evidence base)
Recurrent sinopulmonary infectionsAntibody production defects
  • common variable immunodeficiency (CVID)

  • X-linked agammaglobulinaemia (XLA)

  • transient hypogammagobulinaemia of infancy (THI)

Complement protein deficiencies
Complete blood count with differentialQuantitative serum immunoglobulin (Ig) levels (i.e. IgG, IgA, IgM, IgE)Specific antibody production
  • titres against protein (tetanus, diphtheria) and polysaccharide (pneumococcus, blood group isohaemagglutinins) antigens

Complement protein function
  • CH50 and AH50

Enumeration of lymphocyte subsets including T, B and NK cellsT and B cell in vitro functional assaysQuantification and/or functional assessment of individual complement proteinsGenetic analysisAntimicrobial therapy (III)
  • treatment

  • prophylaxis

Immunoglobulin replacement (IIb)
  • intravenous (IVIG)

  • subcutaneous (SCIG)

Broad infectious susceptibility and failure to thriveSevere combined immunodeficiency (SCID)Other combined immunodeficiencies
  • Wiskott–Aldrich syndrome

  • DiGeorge syndrome

  • Ataxia–telangiectasia

Complete blood count with differentialQuantitative serum immunoglobulin levels (i.e. IgG, IgA, IgM, IgE)Thorough characterisation of infecting pathogensUrgent consultation with a clinical immunologistEnumeration of lymphocyte subsets including T, B and NK cellsT and B cell in vitro functional assaysBiochemical analysis (for adenosine deaminase and purine nucleotide phosphorylase deficiency)Genetic analysisAntimicrobial therapy (III)
  • treatment

  • prophylaxis

Immunoglobulin replacement (IIb)
  • intravenous (IVIG)

  • subcutaneous (SCIG)

Haematopoietic stem cell transplantation (III)Gene therapy (currently experimental)
Granulomatous infections by catalase producing pathogensChronic granulomatous disease (CGD)Complete blood count with differentialMeasurement of phagocyte oxidase activity (preferably using the dihydrorhodamine 123 assay)Genetic analysisAntimicrobial therapy (Ib)
  • treatment

  • prophylaxis (typically trimethoprim–sulfamethoxazole and itraconazole)

Interferon-γ (Ib)Haematopoietic stem cell transplantation (III)
  • The table outlines common presentations of human primary immunodeficiency diseases and provides an overview of investigations and therapeutic options. The quality of the evidence supporting any therapeutic recommendation is categorized using the scheme of Shekell et al.5 Category of evidence: Ia—evidence from meta-analysis of randomised controlled trials; Ib—evidence from at least 1 randomised controlled trial; IIa—evidence from at least 1 controlled study without randomisation; IIb—evidence from at least 1 other type of quasi-experimental study; III—evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case–control studies; IV—evidence from expert committee reports or opinions or clinical experience of respected authorities, or both.