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[]
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):
- 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)
- RAG 1/2 deficiency
- DCLRE1C (Artemis) deficiency
- XLF (protein)/Cernunnos deficiency
- DNA PKcs deficiency
- DNA ligase type IV deficiency
- adenosine deaminase (ADA) deficiency
- reticular dysgenesis
- Omenn syndrome
- CD40 ligand deficiency
- CD40 deficiency
- CD3γ deficiency
- CD8 deficiency
- ICOS deficiency
- ZAP70 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
- STAT5b deficiency
- (XLP1)
- DOCK2 deficiency
- DOCK8 deficiency
- Activated PI3K delta syndrome
- MALT1 deficiency
- BCL10 deficiency
- BCL11B deficiency
- CARD11 deficiency
- IL-21 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]
- Absent B cells with a resultant severe reduction of all types of antibody: X-linked agammaglobulinemia (btk deficiency, or Bruton's agammaglobulinemia), μ-Heavy chain deficiency, l 5 deficiency, Igα deficiency, BLNK deficiency, thymoma with immunodeficiency
- B cells low but present or normal, but with reduction in 2 or more isotypes (usually IgG & IgA, sometimes IgM): common variable immunodeficiency (CVID), CD19 deficiency, TACI (TNFRSF13B) deficiency, BAFF receptor deficiency.
- Normal numbers of B cells with decreased IgG and IgA and increased IgM: Hyper-IgM syndromes
- Normal numbers of B cells with isotype or light chain deficiencies: heavy chain deletions, kappa chain deficiency, isolated IgG subclass deficiency, IgA with IgG subclass deficiency, selective immunoglobulin A deficiency
- Specific antibody deficiency to specific antigens with normal B cell and normal Ig concentrations
- Transient hypogammaglobulinemia of infancy (THI)
Other well defined immunodeficiency syndrome[]
A number of syndromes escape formal classification but are otherwise recognizable by particular clinical or immunological features.[7]
- Immunodeficiency with thrombocytopenia
- Wiskott–Aldrich syndrome
- ARPC1B deficiency
- DNA repair defects not causing isolated SCID:
- Ataxia-telangiectasia
- Ataxia-like syndrome
- Nijmegen breakage syndrome
- Bloom syndrome
- Immunodeficiency–centromeric instability–facial anomalies syndrome (ICF1, 2, 3, and 4)
- RIDDLE syndrome (RNF168 deficiency)
- (POLE deficiency)
- POLE2 deficiency
- LIG1 deficiency
- deficiency
- GINS1 deficiency
- DiGeorge syndrome (when associated with thymic defects)
- TBX1 deficiency
- CHARGE syndrome (CHD7 deficiency or deficiency)
- /FOXN1 deficiency
- Immuno-osseous dysplasias (abnormal development of the skeleton with immune problems):
- Cartilage–hair hypoplasia
- Schimke syndrome
- deficiency
- deficiency
- EXTL3 deficiency
- Hyper IgE syndromes
- Job syndrome (STAT3 deficiency)
- PGM3 deficiency
- Hypohidrotic ectodermal dysplasia
- NEMO deficiency
- IKBA deficiency
- Calcium channel defects
- ORAI1 deficiency
- Transcobalamin 2 deficiency
- (TTC7A deficiency)
- Hepatic venoocclusive disease with immunodeficiency (VODI)
- Vici syndrome
- Purine nucleoside phosphorylase (PNP) deficiency
- (autosomal dominant dyskeratosis congenital)
- Hermansky–Pudlak syndrome type 2
- Chronic mucocutaneous candidiasis
- deficiency
- deficiency
- XL-dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome)
- Hennekam lymphangiectasia-lymphedema syndrome
- Kabuki syndrome
- STAT5b deficiency
- IKAROS deficiency
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]
- Immunodeficiency with hypopigmentation or albinism: Chédiak–Higashi syndrome, Griscelli syndrome type 2
- Familial hemophagocytic lymphohistiocytosis: perforin deficiency, UNC13D deficiency, syntaxin 11 deficiency
- X-linked lymphoproliferative syndrome
- Syndromes with autoimmunity:
- (a) Autoimmune lymphoproliferative syndrome: type 1a (CD95 defects), type 1b (Fas ligand defects), type 2a (CASP10 defects), type 2b (CASP8 defects)
- (b) APECED (autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy)
- (c) IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome)
- (d) CD25 deficiency
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]
- Severe Congenital Neutropenia: due to ELA2 deficiency (with myelodysplasia)
- Severe Congenital Neutropenia: due to GFI1 deficiency (with T/B lymphopenia)
- Elastase deficiency
- Kostmann syndrome (HAX1 deficiency)
- Glycogen storage disease type 1b
- Cohen syndrome
- Cyclic neutropenia
- HYOU1 deficiency
- deficiency
- SMARCD2 deficiency
- 3-Methylglutaconic aciduria
- Leukocyte adhesion deficiency type 1
- Leukocyte adhesion deficiency type 2
- Leukocyte adhesion deficiency type 3
- RAC2 deficiency (Neutrophil immunodeficiency syndrome)
- Beta-actin deficiency
- G-CSF-receptor deficiency
- Papillon–Lefèvre syndrome
- Specific granule deficiency
- Shwachman–Diamond syndrome
- WDR1 deficiency
- Cystic fibrosis
- Chronic granulomatous disease: X-linked or autosomal (CYBA, NCF1, NCF2, NCF4)
- IL-12 and IL-23 β1 chain deficiency
- IL-12p40 deficiency
- Glucose-6-phosphate dehydrogenase deficiency class 1
- Interferon γ receptor 1 deficiency
- Interferon γ receptor 2 deficiency
- STAT1 deficiency
- MKL1 deficiency
- AD hyper-IgE
- AR hyper-IgE
- Pulmonary alveolar proteinosis
- (GATA2 deficiency)
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
- 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
- MDA5 deficiency
- Epidermodysplasia verruciformis
- WHIM syndrome (warts, hypogammaglobulinaemia, infections, myelokathexis)
- EVER1 and EVER2 deficiency
- Herpes simplex encephalitis
- CARD9 deficiency
- Chronic mucocutaneous candidiasis
- 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]
- Familial Mediterranean fever
- Aicardi–Goutières syndrome with TREX1, SAMHD1 or IFIH1 mutations
- (ACP5 mutation)
- STING-associated vasculopathy with onset in infancy
- X-linked reticulate pigmentary disorder
- USP18 deficiency
- (Chronic atypical neutrophilic dermatitis with lipodystrophy)
- Singleton-Merten syndrome
- TNF receptor associated periodic syndrome (TRAPS)
- Hyper-IgD syndrome (Mevalonate kinase deficiency)
- CIAS1-related diseases:
- Muckle–Wells syndrome
- Familial cold autoinflammatory syndrome, types 1, 2, 3, and 4
- Neonatal onset multisystem inflammatory disease
- NLRP1 deficiency
- PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, acne)
- ADAM17 deficiency
- Blau syndrome
- Majeed syndrome (Chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia)
- DIRA (deficiency of the IL-1 receptor antagonist)
- (deficiency of IL-36 receptor antagonist)
- (CAMPS)
- Cherubism
- /ORAS
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]
- C1q deficiency (lupus-like syndrome, rheumatoid disease, infections)
- C1r deficiency (idem)
- C4 deficiency (lupus-like syndrome)
- C2 deficiency (lupus-like syndrome, vasculitis, polymyositis, pyogenic infections)
- C3 deficiency (recurrent pyogenic infections)
- C5 deficiency (Neisserial infections, SLE)
- C6 deficiency (idem)
- C7 deficiency (idem, vasculitis)
- C8a deficiency
- C8b deficiency
- C9 deficiency (Neisserial infections)
- C1-inhibitor deficiency (hereditary angioedema)
- Factor I deficiency (pyogenic infections)
- Factor H deficiency (haemolytic-uraemic syndrome, membranoproliferative glomerulonephritis)
- Factor D deficiency (Neisserial infections)
- Properdin deficiency (Neisserial infections)
- MBP deficiency (pyogenic infections)
- MASP2 deficiency
- Paroxysmal nocturnal hemoglobinuria
- Properdin deficiency
- Factor I deficiency
Phenocopies of primary immune deficiencies[]
- Autoimmune lymphoproliferative syndrome
- RAS-associated autoimmune leukoproliferative disorder
- Atypical hemolytic uremic syndrome
- Good syndrome
References[]
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ "Common Variable Immune Deficiency". NORD (National Organization for Rare Disorders). Retrieved 5 March 2019.
- ^ a b c d e f g h 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.
- Immunodeficiency