Types of primary immunodeficiency

Over 360 different primary immunodeficiencies (PIDs) have been identified, with about 20 of these accounting for over 90 per cent of cases. This means that many conditions are extremely rare: indeed for some conditions, fewer than ten cases have been identified.

Classification of PIDs

Every two years an international committee of experts meets to revise and update this classification, adding new conditions and information on the genes that cause PIDs.

At present, PIDs are grouped or classified under eight major subcategories based on what cells or parts of the immune system are affected.

These subcategories are:

  • Combined immunodeficiencies. This includes both SCID (severe combined immune deficiency) and CID (combined immune deficiency). There are many disorders in this group and many require bone marrow transplant in early life.
  • Well-defined syndromes with immunodeficiency. This group includes conditions which often have a number of non-immune system features, such as DiGeorge syndrome or Hyper IgE Syndrome.
  • Predominantly antibody deficiencies. This is a large group of both severe and mild disorders where the main clinical features relate to low levels of antibodies or their inability to protect against major infections, including the conditions common variable immune deficiency (CVID) and X-linked agammaglobulinaemia (XLA).
  • Diseases of immune dysregulation. This is a group that includes disorders where the immune system cant control specific viruses or cannot “switch off” ones activated.  It includes the disorders that cause HLH (Haemophagocytic lympohistiocytosis) and many where there is autoimmunity such as ALPS (autoimmune lymphoproliferative syndrome). 
  • Congenital defects of phagocyte number, function, or both. This group includes the neutrophil disorders, including chronic granulomatous disorder (CGD), Leucocyte adhesion deficiency (LAD) and GATA2 deficiency.
  • Defects in innate immunity. These include the chronic mucocutaneous candidiasis (CMC) conditions such as STAT1 dysregulation or those that predispose to early life infection severe bacterial infection such as IRAK4 deficiency.
  • Autoinflammatory disorders, a group of inherited fever syndromes such as Muckle–Wells Syndrome and Familial Mediterranean Fever.
  • Complement deficiencies. This includes disorders that predispose to specific infection (such as C8 deficiency) and those with angioedema (C1 esterase deficiency, HAE).

You can download the 2017 list of known primary immunodeficiencies here.

This page was reviewed by the Chair of the Medical Advisory Panel, January  2019.