in hyper IgM syndrome, why does pneumocystis jiroveci infection increase particularly?
Hyper-IgM syndrome can be caused by at least four different molecular genetic defects, the most common of which affects the gene on the X chromosome encoding CD40 ligand, a T-cell surface molecule responsible for instructing B cells to switch from IgM to IgG, IgA, and IgE production. Other forms of the disorder involve the autosomal genes CD40, AID, and UNG, all of which are responsible for B-cell class switching. As the name suggests, all forms of this disorder are characterized by elevated (or normal) IgM levels in the face of reduced levels of IgG and IgA.
The clinical presentation of hyper-IgM syndrome is most commonly related to certain infections. The form caused by a deficiency in CD40 ligand often presents with opportunistic infections such as P. jirovecii pneumonia and may be associated with neutropenia. This form of the X-linked hyper-IgM syndrome is also associated with Cryptosporidium infections of the biliary tree, leading to sclerosing cholangitis.