What is the hyper IgM syndrome?
The hyper-IgM immunodeficiency syndrome (type 1) is characterized by extremely low levels of IgG, IgA, and IgE and either a normal or markedly elevated concentration of polyclonal IgM. Patients develop both recurrent pyogenic infections and opportunistic infections like P. jirovecii pneumonia. There is also an increased frequency of autoimmune disorders (autoimmune cytopenias, arthritis, nephritis) and malignancy (lymphoma, tumors of GI tract). The defect causing this x-linked syndrome is an abnormal gene resulting in a defective CD40 ligand (CD 154) on the surface of activated CD4+ T cells. This mutation results in the failure of T cells to interact with CD40 on B cells. This lack of B-cell signaling by T cells results in the B cell failing to undergo isotype switching and produce only IgM. Two other types (2 and 3) of this syndrome have different genetic defects and inheritance patterns. Other mutations that affect immune globulin isotype switching and result in laboratory abnormalities that are similar to those seen in patients with defective expression of CD40L are inherited in an autosomal recessive manner and include mutations in genes for CD40, NFκB essential modulator (NEMO), activated cytidine deaminase (AID), and uracil deglycosylase (UNG).