Hyper-IgM Syndrome

Summary

Hyper-IgM Syndrome is an X-linked recessive immunodeficiency characterized by an excess of IgM, but nearly nonexistent levels of IgG, IgA, and IgE. This occurs due to defective class-switching in B-cells, leaving B-cells only able to produce IgM antibodies. The mechanistic cause is a defective CD40-ligand on Helper T-Cells, which normally binds to CD40 receptor on B-cells to promote B-cell activation and class switching. Clinically, these patients present with recurrent infections secondary to immunodeficiency (due to impaired humoral immunity), with significant lymphoid hyperplasia. Labs will reveal excessively high levels of IgM, but low levels of all other antibodies.

Key Points

• Hyper-IgM Syndrome
  • Defective CD40L on Helper T-cells
    • Required for B-cell Activation and class-switching
  • Results in class-switching defect (from IgM)
    • B-cells produce IgM by default, but require class-switching to produce other isotypes, such as IgG, IgA, and IgE
  • X-linked recessive
    • Generally affects male patients
  • Presentation
    • Immunodeficiency
      • Recurrent respiratory infections secondary to deficient lgA
    • Lymphoid hyperplasia
      • large tonsils and palpable lymph nodes
        • Lack of other antibody types causes compensatory B-cell proliferation, but does not fix root cause (impaired class-switching)
        • Biopsy reveals disorganized lymph nodes with failure to produce germinal centers
    • Elevated levels of IgM
      • Nearly non-existent IgA, IgG, and IgE levels