PID - Human Inborn Errors of Immunity D81.-D84.

Last updated on: 24.05.2022

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Definition
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The term primary immun odeficiencies (synonym: PID/immunodeficiency syndromes/immunodeficiency diseases) covers more than 300 different diseases of the immune system, which are characterized by a temporary or irreversible disturbance of the immune function, in which the immunodeficiency is congenital, occurs in families and/or can be inherited.

Secondary or acquired immunodeficiencies: The PID group with congenital defects is contrasted with acquired or secondary immunodeficiencies. The best known example of this is AIDS (acquired immune deficiency syndrome).

Clinically, primary immunodeficiencies are usually manifested by a pathological susceptibility to infections. Typical warning signs are hidden behind the acronyms ELVIS (pathogen, unusual; localization, atypical; course, long; intensity, severe; sum, very frequent) and GARFIELD (granulomas, autoimmunity, recurrent fever, eczema, lymphoproliferation, intestinal inflammation). PID can manifest in all organs, with skin, lung, and intestine being the most commonly affected.

The following table reflects the currently valid classification of Primary Immunodeficiencies according to the IUIS Classification 2021.

Classification
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Primary immunodeficiencies (PID) according to IUIS classification (2021)

1.primary immunodeficiencies /combined T/B/(NK)-cell immunodeficiencies incl. "SCID".

  • 1.1.SCID (T-/B+)
  • 1.2.SCID (T-/B-)
  • 1.3 Combined immunodeficiencies (CID) less severe than SCID

2. primary immunodeficiencies /T- and B-cell immunodeficiencies with syndromal features

  • 2.1 PID with congenital thrombocytopenia
  • 2.2. DNA repair defects
  • 2.3. thymic defects with additional abnormalities
  • 2.4. immunosseous dysplasias
  • 2.5. hyper IgE syndromes
  • 2.6. disorders of vitamin B12 and folic acid metabolism
  • 2.7 Anhidrotic ectodermal dysplasias with immunodeficiencies (EDA-ID)
  • 2.8. calcium channel defects
  • 2.9 Other defects (Ig decreased, IgA absent)

3) Primary immunodeficiencies/antibody deficiency as leading symptom

  • 3.1. severe reduction of all immunoglobulin isotypes with severely reduced or absent B cells
  • 3.2. severe reduction of at least 2 Ig isotypes (IgG and IgA)B cell count normal or decreased
  • 3.3. reduction of IgG and IgA with normal/increased IgM and normal B cell count
  • 3.4. isotype or light chain deficiency with normal B cells

4. primary immunodeficiencies/immune dysregulations

  • 4.1.Familial hemophagocytic lymphohistiocytoses (FHL)
  • 4.1.1.Familial hemophagocytic lymphohistiocytoses (FHL)
  • 4.1.2 Familial hemophagocytic lymphohistiocytoses with hypopigmentation
  • 4.2 Genetic defects of regulatory T cells
  • 4.3 Autoimmunity with or without lymphoproliferation
  • 4.4. immune dysregulation with colitis
  • 4.5 Autoimmune lymphoproliferative syndromes (ALPS; Canale Smith syndrome)
  • 4.6. immunodysregulation with abnormality to EBV/lymphoproliferation

5. primary immunodeficiencies/defects of phagocyte number and/or function

  • 5.1 Defects of neutrophil development, congenital neutropenia
  • 5.2. defects of motility
  • 5.3. defects in the respiratory burst
  • 5.4 Other non-lymphocytic defects

6. primary immunodeficiencies/defects of intrinsic and natural immunity

  • 6.1 Mendelian Susceptibility to Mycobacterial Disease (MSMD)
  • 6.2 Epidermodysplasia verruciformis
  • 6.3. predisposition to severe viral infections
  • 6.4. herpes simplex encephalitis
  • 6.5. disposition to invasive fungal infections
  • 6.6. chronic mucocutaneous candidiasis (CMC)
  • 6.7. disorders of TIR (Toll-like and Interluekin-IR) signaling with susceptibility
  • 6.8. other congenital defects of immunity involving non-hematopoietic tissues
  • 6.9 Other congenital defects in leukocytes

7. primary immunodeficiencies/autoinflammatory diseases

  • 7.1 Type I interferonopathies
  • 7.2 Defects of the inflammasome
  • 7.3 Non-inflammasome-dependent autoinflammation

8. primary immunodeficiencies/complementary defects

9. primary immunodeficiencies/bone marrow failure

10. primary immunodeficiencies/phenocopies (DD of primary immunodeficiencies)

  • 10.1.phenocopies associated with somatic mutations
  • 10.2.phenocopies associated with autoantibodies

Occurrence/Epidemiology
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In Europe, about 1.5 million people live with a congenital primary immunodeficiency (PID). Despite the possibilities of modern antibiotic therapy, those affected suffer from frequent infections that are difficult to control. In Germany, it is currently estimated that >100,000 people are affected. Early diagnosis is an important prerequisite for significantly improving the prognosis and quality of life of patients.

Diagnostics
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After a detailed anamnesis and clinical examination, the further diagnostic procedure is performed according to consensus and evidence-based guidelines. In individual complex cases that cannot be clarified with previous methods, a so-called "whole exome sequencing" may be indicated.

Therapy
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Numerous forms of therapy are now available (e.g. regular administration of antibody preparations, enzyme replacement therapy, modern antibiotics or antimycotics, transplantation of stem cells from bone marrow or peripheral blood, and gene therapy approaches).

Note: Since August 2019, newborns are screened for severe congenital immunodeficiencies (SCID).

Note(s)
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The classification of primary immunodeficiencies is published at multi-year intervals as a report of a scientific working group of the International Union of Immunological Societies (IUIS). The present classification is based on the work of Tangye SG et al (2020) and Tangye SG et al (2021).

Literature
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  1. Bousfiha A et al. (2015) The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies. J Clin Immunol 35:727-738.
  2. Bousfiha A et al (2020) Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 40:66-81.
  3. Tangye SG et al (2020) Human Inborn Errors of Immunity: 2019 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 40:24-64.
  4. Tangye SG et al. (2021) The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update by the IUIS Committee. J Clin Immunol 41:666-679.

Disclaimer

Please ask your physician for a reliable diagnosis. This website is only meant as a reference.

Last updated on: 24.05.2022