X-linked hyper-IgM syndrome (CD40L deficiency)

X-linked immunodeficiency with hyperimmunoglobulin M (XHIM) is caused by the absence of CD40 ligand (TNFSF5 or CD154), which is normally expressed on activated CD4+ T cells. Absence of TNFS5 interrupts B cells differentiation by somatic hypermutation and heavy-chain switch from IgM to other immunoglobulin isotypes. Somatic hypermutation and immunoglobulin class switching are required to make high-affinity functional antibodies.

Alternative names


Hyper-IgM immunodeficiency, X-linked

Hyper-IgM syndrome 1

Hyper-IgM syndrome; HIGM; IHIS

Immunodeficiency 3 Dysgammaglobulinemia, type 1

Tumor necrosis factor superfamily member 5 (CD40L, CD154)


  • Combined B and T cell immunodeficiencies
    • Hyper-IgM syndrome




#308230 Immunodeficiency with hyper-IgM, type 1; HIGM1

*300386 Tumor necrosis factor ligand superfamily, member 5

Cross references

Genetically related immunodeficiencies

IDR factfile for non hyper-IgM syndrome


1/1,000,000 live births in males