List of primary immunodeficiencies

This is a list of primary immunodeficiencies (PID), which are immune deficiencies that are not secondary to another condition.

The International Union of Immunological Societies recognizes nine classes of primary immunodeficiencies, totaling approximately 430 conditions.[1][2] A 2014 update of the classification guide added a 9th category and added 30 new gene defects from the prior 2009 version.[3][4] The most recent classification was released in 2019.[5] The number of identified conditions continues to grow over time as more research is done.

The impact of primary immunodeficiencies ranges from mild to severe based on the condition.[6]

Combined T and B–cell immunodeficiencies

Genetic immunodeficiencies. (In general, those on the left are in Table I, while those on the right are in Table II, but there are exceptions.)

In these disorders both T lymphocytes and often B lymphocytes, regulators of adaptive immunity, are dysfunctional or decreased in number. The main members are various types of severe combined immunodeficiency (SCID).[7]

  • T-/B+ SCID (T cells predominantly absent):
    • γc deficiency
    • JAK3 deficiency
    • Interleukin-7 receptor-α deficiency
    • CD45 deficiency
    • CD3δ, CD3ε, or CD3ζ deficiency
    • Coronin-1A deficiency
    • LAT (gene) deficiency
  • T-/B- SCID (both T and B cells absent)
  • Omenn syndrome
  • CD40 ligand deficiency
  • CD40 deficiency
  • CD3γ deficiency
  • CD8 deficiency
  • ICOS deficiency
  • ZAP70 deficiency
  • Ca++ channel deficiency
  • MHC class I deficiency (with mutations in TAP1, TAP2, TAPBP, or B2M)
  • MHC class II deficiency (with mutations in CIITA, RFXANK, RFX5, or RFXAP)
  • CD25 deficiency
  • CD27 deficiency
  • STAT5b deficiency
  • ITK deficiency
  • SH2D1A deficiency (XLP1)
  • MAGT1 deficiency
  • DOCK2 deficiency
  • DOCK8 deficiency
  • RhoH deficiency
  • Activated PI3K delta syndrome
  • MALT1 deficiency
  • BCL10 deficiency
  • BCL11B deficiency
  • CARD11 deficiency
  • MST1 deficiency
  • TCRα deficiency
  • LCK deficiency
  • IL-21 deficiency
  • IL-21R deficiency
  • UNC119 deficiency
  • NIK deficiency
  • OX40 deficiency
  • IKBKB deficiency
  • TFRC deficiency
  • Moesin deficiency
  • RELB deficiency
  • Cartilage hair hypoplasia
  • LRBA deficiency

Predominantly antibody deficiencies

In primary antibody deficiencies, one or more isotypes of immunoglobulin are decreased or don't function properly. These proteins, generated by plasma cells, normally bind to pathogens, targeting them for destruction.[7]

Other well defined immunodeficiency syndrome

A number of syndromes escape formal classification but are otherwise recognizable by particular clinical or immunological features.[7]

Diseases of immune dysregulation

In certain conditions, the regulation rather than the intrinsic activity of parts of the immune system is the predominant problem.[7]

Congenital defects of phagocyte number, function, or both

Phagocytes are the cells that engulf and ingest pathogens (phagocytosis), and destroy them with chemicals. Monocytes/macrophages as well as granulocytes are capable of this process. In certain conditions, either the number of phagocytes is reduced or their functional capacity is impaired.[7]

Defects in innate immunity

Several rare conditions are due to defects in the innate immune system, which is a basic line of defense that is independent of the more advanced lymphocyte-related systems. Many of these conditions are associated with skin problems.[7]

  • Interleukin 12 receptor, beta 1 deficiency
  • IL-12p40 deficiency
  • Interferon gamma receptor 1 deficiency
  • Interferon gamma receptor 2 deficiency
  • Tyk2 deficiency
  • JAK1 loss-of-function
  • ISG15 deficiency
  • RORc deficiency
  • STAT1 deficiency, gain-of-function mutation
  • STAT2 deficiency
  • IRF7 deficiency
  • CD16 deficiency
  • IRF8 deficiency
  • IFNAR2 deficiency
  • TLR pathway deficiencies
    • IRAK4 deficiency
    • IRAK1 deficiency
    • MyD88 deficiency
    • TIRAP deficiency
  • MDA5 deficiency
  • Epidermodysplasia verruciformis
    • WHIM syndrome (warts, hypogammaglobulinaemia, infections, myelokathexis)
    • EVER1 and EVER2 deficiency
  • Herpes simplex encephalitis
    • TLR3 deficiency
    • TRAF3 deficiency
    • TRIF deficiency
    • TBK1 deficiency
    • IRF3 deficiency
  • CARD9 deficiency
  • Chronic mucocutaneous candidiasis
    • IL17RA or IL17RC deficiency
  • Trypanosomiasis
  • RPSA deficiency with congenital asplenia
  • HMOX deficiency with congenital asplenia
  • CLCN7 deficiency with osteoporosis
  • OSTM1 deficiency with osteoporosis
  • Hidradenitis suppurativa

Autoinflammatory disorders

Rather than predisposing for infections, most of the autoinflammatory disorders lead to excessive inflammation. Many manifest themselves as periodic fever syndromes. They may involve various organs directly, as well as predisposing for long-term damage (e.g. by leading to amyloid deposition).[7]

Complement deficiencies

The complement system is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that can bind pathogens and form a membrane attack complex. Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to autoimmune conditions.[7]

Phenocopies of primary immune deficiencies

References

  1. Bousfiha, Aziz; Jeddane, Leïla; Picard, Capucine; Ailal, Fatima; Bobby Gaspar, H.; Al-Herz, Waleed; Chatila, Talal; Crow, Yanick J. (2018). "The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies". Journal of Clinical Immunology. 38 (1): 129–143. doi:10.1007/s10875-017-0465-8. ISSN 0271-9142. PMC 5742599. PMID 29226301.
  2. Tangye, Stuart G.; Al-Herz, Waleed; Bousfiha, Aziz; Chatila, Talal; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Holland, Steven M.; Klein, Christoph; Morio, Tomohiro; Ochs, Hans D. (2020-01-01). "Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee". Journal of Clinical Immunology. 40 (1): 24–64. doi:10.1007/s10875-019-00737-x. ISSN 1573-2592. PMC 7082301. PMID 31953710.
  3. Waleed Al-Herz; Aziz Bousfiha; Jean-Laurent Casanova; et al. (2014). "Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency" (PDF). Frontiers in Immunology. 5 (162): 1–33. doi:10.3389/fimmu.2014.00162. PMC 4001072. PMID 24795713.
  4. Notarangelo L, Casanova JL, Conley ME, et al. (2006). "Primary immunodeficiency diseases: an update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005". J. Allergy Clin. Immunol. 117 (4): 883–96. doi:10.1016/j.jaci.2005.12.1347. PMID 16680902.
  5. Tangye, Stuart G.; Al-Herz, Waleed; Bousfiha, Aziz; Chatila, Talal; Cunningham-Rundles, Charlotte; Etzioni, Amos; Franco, Jose Luis; Holland, Steven M.; Klein, Christoph; Morio, Tomohiro; Ochs, Hans D. (2020-01-01). "Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee". Journal of Clinical Immunology. 40 (1): 24–64. doi:10.1007/s10875-019-00737-x. ISSN 1573-2592. PMC 7082301. PMID 31953710.
  6. "Common Variable Immune Deficiency". NORD (National Organization for Rare Disorders). Retrieved 5 March 2019.
  7. 1 2 3 4 5 6 7 8 Notarangelo LD, Fischer A, Geha RS, et al. (December 2009). "Primary immunodeficiencies: 2009 update: The International Union of Immunological Societies (IUIS) Primary Immunodeficiencies (PID) Expert Committee". J. Allergy Clin. Immunol. 124 (6): 1161–78. doi:10.1016/j.jaci.2009.10.013. PMC 2797319. PMID 20004777.
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