Utility: 1) Diagnostic screen for X-linked (CD40L) and autosomal recessive (CD40)
hyper IgM syndrome.
2) Detection of carrier status in female relative of X-linked hyper IgM syndrome.
Specimen: 4 - 10 mL peripheral blood in sodium heparin (green top).
CPT codes: 86359, 86360, 86355, 86357, 88184, 88185 x 6, 88187.
Clinical indication/general description
Hyper-IgM (HIGM) syndrome is a group of primary immunodeficiencies characterized by the absence of immunoglobulin class-switching. Patients with HIGM syndrome exhibit low serum IgG, IgA and IgE levels with normal or elevated serum IgM levels. HIGM syndrome can be caused by mutations in CD40LG (Type 1, X-linked HIGM syndrome), CD40 (Type 3, autosomal recessive HIGM syndrome), activation-induced cytidine deaminase (AID, Type 2, autosomal recessive), or uracil-DNA glycosylase (UNG, Type 5, autosomal recessive). T lymphocytes up-regulate CD40L upon activation that interacts with CD40 on B cells resulting in immunoglobulin class switching, a process that requires AID and UNG. CD40L also interacts with CD40 on monocytes resulting in activation of cell-mediated immune responses. HIGM patients with mutations in CD40 or CD40LG are prone to a variety of bacterial and viral infections as well as opportunistic infections with Pneumocystis jiroveci or Cryptosporidium. HIGM patients, due to mutations in AID or UNG, suffer from recurrent infections but do not show susceptibility to opportunistic infections.
X-linked hyper IgM (XL-HIGM, Type 1) presents with the inability of activated T helper cells (CD3+CD4+) to up-regulate CD40L (CD154) surface expression. Peripheral blood cells are activated pharmacologically and the expression of CD40L is determined by flow cytometry. Female carriers show two populations of CD4 cells: one with CD40L expression and one without expression. This assay also detects CD40 expression on B cells and monocytes (autosomal recessive, Type 3).
Note: This assay does not detect defects in UNG or AID.