CD40 (CD40 molecule) is a protein coding gene located on chromosome 20q13.12. The CD40 gene is a member of the TNF receptor superfamily. CD40 is the receptor for CD40LG (TNFSF5). CD40-CD40L interaction is an essential signal for B cell proliferation, activation marker expression, immunoglobulin production, and isotype switching. The CD40-CD40L interaction is also required for the formation of memory B cells and germinal centers, and signaling through CD40 prevents apoptosis of germinal center B cells (Laman JD et al. 2017). Deficient expression of CD40L in humans results in the inability to produce isotypes other than IgM (hyper-IgM syndrome) and the absence of germinal centers. The interaction between CD40 and its ligand is required for amyloid beta-induced microglial activation and is therefore considered an early event in the pathogenesis of Alzheimer's disease.
Defects affecting the DC40 gene are the cause of
- the autosomal recessive hyper IgM immunodeficiency type 3 (HIGM3)
- the X chromosomal recessive immunodeficiency with hyper IgM, type 1 (see below Hyper IgM syndromes).
- The CD40 gene SNP rs1883832 is associated with an increased risk of developing immune thrombocytopenic purpura (ITP) in the Egyptian population (AbdelGhafar MT et al. 2020).