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. A 2014 update of the classification guide added a 9th category and added 30 new gene defects from the prior 2009 version. The most recent classification was released in 2019. 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.
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).
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) 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 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.
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.
Immunodeficiency with thrombocytopenia Wiskott–Aldrich syndrome WIP deficiency 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) PMS2 deficiency RIDDLE syndrome (RNF168 deficiency) MCM4 deficiency FILS syndrome (POLE deficiency) POLE2 deficiency LIG1 deficiency NSMCE3 deficiency Hebo deficiency GINS1 deficiency DiGeorge syndrome (when associated with thymic defects) TBX1 deficiency CHARGE syndrome (CHD7 deficiency or SEMA3E deficiency) Winged helix/FOXN1 deficiency Chromosome 10p13-p14 deletion Immuno-osseous dysplasias (abnormal development of the skeleton with immune problems): Cartilage–hair hypoplasia Schimke syndrome MYSM1 deficiency MOPD1 deficiency EXTL3 deficiency Hyper IgE syndromes Job syndrome (STAT3 deficiency) Comel-Netherton syndrome PGM3 deficiency Hypohidrotic ectodermal dysplasia NEMO deficiency IKBA deficiency Calcium channel defects ORAI1 deficiency STIM1 deficiency Transcobalamin 2 deficiency Immunodeficiency with multiple intestinal atresias (TTC7A deficiency) Hepatic venoocclusive disease with immunodeficiency (VODI) Vici syndrome Purine nucleoside phosphorylase (PNP) deficiency AR-DKC (autosomal dominant dyskeratosis congenital) Hermansky–Pudlak syndrome type 2 Chronic mucocutaneous candidiasis HOIL1 deficiency HOIP deficiency XL-dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome) Hennekam lymphangiectasia-lymphedema syndrome Kabuki syndrome MTHFD1 deficiency 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.
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.
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