Activated PI3K delta syndrome

Activated PI3K delta syndrome is a primary immunodeficiency disease caused by activating gain of function mutations in the PIK3CD gene.[7][8][2] Which encodes the p110δ catalytic subunit of PI3Kδ, APDS-2 (PASLI-R1) is caused by exon-skipping mutations in PIK3R1 which encodes for the regulatory subunit p85α. APDS and APDS-2 affected individuals present with similar symptoms, which include increased susceptibility to airway infections, bronchiectasis and lymphoproliferation.

Activated PI3K delta syndrome
Other namesimmunodeficiency 14, p110δ-activating mutation causing senescent T cells, PASLI
Activated PI3K Delta Syndrome is autosomal dominant
SymptomsImmunodeficiency, Lymphadenopathy[1]
CausesMutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform[2][3]
Diagnostic methodGenetic testing[4]
TreatmentAntiviral therapy[5][6]

Symptoms and signs

The signs and symptoms of activated PI3K Delta Syndrome are consistent with the following:[1]

Cause

In terms of genetics, activated PI3K Delta Syndrome is autosomal dominant, a mutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform is the reason for this condition (located at chromosome 1p36.) [2][3]

Mechanism
PI3kinase

The pathophysiology of activated PI3K delta syndrome has several aspects.[2] The normal function has P110δ (PI3K) involved in immune system regulation.[9]

P110δ effect is not limited to the immune system; P110δ has a presence in transformed epithelial cells and cell adhesion molecules (airway inflammation), and research has been done on the possibility of P110δ in the nervous system.[10]

Activated PI3K delta syndrome effect indicates affected individuals are likely to have activation-induced cell death.[2] Normally, PI3K-delta signaling assists B cells and T cells to mature; however, overactive PI3K-delta has an effect on the B and T cell differentiation (the process by which cells eventually are different from one another[11]).

Consequently, there is an inability to confront an infection, as well as early cell death. Furthermore, overproduction of said signal can cause lymphadenopathy (which is an enlargement of lymph nodes[12]) due to excess white blood cells.[7]

Diagnosis

In order to ascertain if an individual has activated PI3K delta syndrome, usually one finds atypical levels of immunoglobulins. Methods to determine the condition are the following:[4]

Treatment
Amoxicillin(antibiotic)

Infections for this condition, are treated or prevented in the following general ways:[5][6]

See also

References
  1. "PASLI disease | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2017-06-09.
  2. "OMIM Entry - # 615513 - IMMUNODEFICIENCY 14; IMD14". www.omim.org. Retrieved 2017-06-10.
  3. Reference, Genetics Home. "PIK3CD gene". Genetics Home Reference. Retrieved 2017-06-10.
  4. "PI3 Kinase Disease | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 2017-06-10.
  5. "Immunodeficiency (Primary and Secondary). Information". patient.info. Retrieved 2017-06-11.
  6. "Bronchiectasis Treatment & Management: Approach Considerations, Supportive Treatment, Antibiotic Therapy". 2017-02-17. Cite journal requires |journal= (help)
  7. Reference, Genetics Home. "activated PI3K-delta syndrome". Genetics Home Reference. Retrieved 2017-06-09.
  8. Collard, Harold R.; Richeldi, Luca (2017-02-18). Interstitial Lung Disease E-Book. Elsevier Health Sciences. p. 9. ISBN 9780323480253.
  9. "PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2017-06-11.
  10. Schoenberger, Stephen P.; Katsikis, Peter D.; Pulendran, Bali (2015-08-31). Crossroads Between Innate and Adaptive Immunity V. Springer. p. 121. ISBN 9783319157740.
  11. Prasad, Keder N. (2012-12-06). Regulation of Differentiation in Mammalian Nerve Cells. Springer Science & Business Media. p. 2. ISBN 9781468481129.
  12. Fleisher, Gary R.; Ludwig, Stephen (2010). Textbook of Pediatric Emergency Medicine. Lippincott Williams & Wilkins. p. 378. ISBN 9781605471594.

Further reading
Classification
External resources
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