CD40 Gene

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).

1. AbdelGhafar MT et al (2020) Impact of CD40 gene polymorphisms on the risk of immune thrombocytopenic purpura. Gene 736:144419.
2. Cognasse F et al (2022) Platelets as Key Factors in Inflammation: Focus on CD40L/CD40. Front Immunol13:825892.
3. Laman JD et al (2017) Functions of CD40 and Its Ligand, gp39 (CD40L). Crit Rev Immunol 37(2-6):371-420.