Utility: 1) Functional evaluation of toll-like receptors (TLRs).
2) Diagnostic screen for primary immunodeficiency related to the innate immune system.
Specimen: 8 - 15 mL peripheral blood in sodium heparin (green top).
CPT codes: 86353 x 3, 88184, 88185, 81887.
Clinical indication/general description
TLRs recognize a variety of molecules conserved in microorganisms that are not present in humans, such as lipopolysaccharides in bacteria and double stranded RNA of viruses. Defects in signaling through TLR have been found in humans with increased susceptibility to infections. Defects in MyD88 and IRAK-4, molecules required for TLR4 signaling, have been detected in patients with recurrent, invasive pneumococcal or staphylococcal infections, and defects in TLR3 and UNC-93B have been found in patients with recurrent herpes encephalitis. Infants and young children are particularly susceptible to infections when they have defects in TLRs since the adaptive immune system has not developed at this age to offer protection. Any children with recurrent or severe pneumococcal, staphylococcal infections or herpes encephalitis should be evaluated for defective TLR signaling.
A functional flow cytometric-based assay tests TLR4 function by assessing the ability of monocytes to produce tumor necrosis factor-alpha (TNF-a). Peripheral blood is incubated with lipopolysaccharide and TNF-a production is measured. This assay will detect defects in MyD88 and IRAK-4, proteins involved in TLR4 signaling that have been associated with recurrent, invasive pneumococcal and staphylococcal infections.