<b>Background</b>: Mutations in CD40 ligand gene (<i>CD40L</i>) affecting immunoglobulin class-switch recombination and somatic hypermutation can result in X-Linked Hyper IgM Syndrome (HIGM1, XHIGM), a kind of rare serious primary immunodeficiency disease (PID) characterized by the deficiency of IgG, IgA and IgE and normal or increased serum concentrations of IgM.
Molecular analysis revealed a functional mutation across the CD40L gene (NM_000074: exon5: c.T464C) resulted in amino acid change p.L155P attributed to X-linked hyper IgM syndrome.
Mutations in the CD40 ligand (CD40L) gene (<i>CD40LG</i>) lead to X-linked hyper-IgM syndrome (X-HIGM), which is a primary immunodeficiency (PID) characterized by decreased serum levels of IgG and IgA and normal or elevated IgM levels.
Enhanced pAKT was not observed in B cells of healthy controls, patients with common variable immunodeficiency, and hyper IgM syndrome due to CD40L deficiency.
X-linked hyper-immunoglobulin M (hyper-IgM) syndrome (XHIM) is a primary immunodeficiency due to mutations in CD40 ligand that affect immunoglobulin class-switch recombination and somatic hypermutation.
The diagnosis of XHIGM was ultimately confirmed by detection of elevated serum IgM concentration, decreased serum IgG and IgE concentration, and identification of a mutation c.654C>A (p.C218X) in CD40L gene.
The clinical manifestations of XHIGM in our patient had several unique features, including the presentation with PAP, normal serum IgA, and expression of non-functional CD40L on activated T cells.
The long-term outcome of X-linked hyper-IgM syndrome (XHIM) caused by mutations in CD40LG is poor, and the only curative treatment is hematopoietic stem cell transplantation (HSCT).
Our study strongly suggests that genetic diagnosis for XHIGM should always be performed when clinical data support this diagnosis and CD40L protein is present.