Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology
Which PIDD is most common?
Antibody (50%), T cell defects (20%), phagocyte def (20%), Complement (2%). Mnemonic: 50-20-20-2
Primary Immunodeficiency (PIDD): pH CCC
CGD mnemonic: 3
3 letters - CGD
3 stages of testing: DHR, immunoblot, genotyping
3 prophylaxis modalities: TMP-SMX, antifungal, INF-gamma
JAK3 defect causes a form of SCID.
"Just fine" B cells (T-/B+/NK-)
Key steps of the JAK-STAT pathway. Image source: Wikpedia, public domain.
Cytokine Signaling. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.
Type I cytokine receptors are mediated through JAK/STAT and bind: IL-2, 3, 4, 5, 6, 7, 9, 10, 12, 13, 15, GM-CSF.
LAD type 2
Fucose, Sialyl LewisX (SLeX)
Stem cell CD 34+
Plasma cell CD 38+
Stem cell CD 34
Wiskott-Aldrich CD 43 defect
CD40L on T helpers (CD4+)
FAS-L on CTL 9CD8+)
CD40 on B cells
FAS ("death signal") on cells to be killed by CTLs
CD40 and CD40L defects are among the causes of HyperIgM syndrome.
Four - CXCR4 (CD4) - also involved in WHIM syndrome (PIDD)
A mutation of CXCR4 causes a phagocytic defect called WHIM syndrome (Warts, Hypogammaglobulinemia, Infection, and Myelokathexis). Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). Myelokathexis causes severe chronic leukopenia and neutropenia.
ZAP 70 binds to the Zeta chain (CD247) of the T-cell receptor.
Zeta-chain-associated protein kinase 70 (70 is the molecular weight in kDa)
ZAP70 deficiency is a form of SCID (T-/B+/NK+), one of the few SCID forms with palpable LN.
T-cell receptor complex with TCR-α and TCR-β chains. Image source: Wikipedia.
Dose of IVIG in PIDD
4 letter words:
All of the following are causes of hyper-IgM syndrome except:
A. CD40L deficiency on B cells
B. AID defect (activation-induced cytidine deaminase gene)
C. CD40 deficiency on B cells
D. CD40L deficiency on T cells
E. UNG defect
Answer: A. There is no CD40L on B cells. CD40L is on T cells.