Anthony Hoffnagle was well until after 6 months of age when he was hospitalized for pneumonia 5 times in the same year. A consultation with an immunologist revealed normal numbers of B cells and T cells, slightly elevated IgM, and a marked decrease in IgG and IgA. He was diagnosed with X-linked hyper IgM syndrome. Based upon the information in the previous questions, what is the most important gene that might be defective that would result in lack of class switch to IgG or IgA

CD40L  

Explanation:

The CD40 ligand (CD40L) protein is a transmembrane glycoprotein which is expressed on activated T cells and belongs to the tumor necrosis factor (TNF) superfamily. The hyper IgM syndrome is caused by mutations in the CD40L gene, where the defective protein can no longer bind CD40 on antigen-presenting cells. The X-linked Hyper IgM syndrome is characterized by abnormal levels of immunoglobulins, i.e., low levels of IgG and IgA, and increased/normal levels of IgM. Because CD40L gene is located on the X chromosome, this disorder is observed much more frequently in males than in females.

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