Assist in diagnosis of innate immunodeficiencies when genetic defects of the innate immune system are suspected in individuals negative for other immunodeficiencies (eg, no detectable abnormality of antibody function, complement activity, neutrophil function, or cell-mediated immunity).
Cell Culture/Quantitative Multiplex Bead Assay
Collect control specimen from a healthy individual unrelated to patient at approximately the same time as and under similar conditions to the patient.
Green (sodium heparin) (patient) AND green (sodium heparin) (control). Also acceptable: Yellow (ACD solution A) (patient) AND yellow (ACD solution A) (control). Patient and control specimens must be collected within 48 hours of test performance.
Transport 10 mL whole blood (patient) AND 10 mL whole blood (control) in original collection tubes. (Min: 7 mL (patient) AND 7 mL (control)) Do not refrigerate or freeze. LIVE CELLS REQUIRED.
Infant Minimum: 3 mL whole blood (patient) AND 7 mL whole blood (control).
CRITICAL ROOM TEMPERATURE.
Yellow (ACD Solution B). Refrigerated or frozen specimens.
Ambient: 48 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
New York State Clients: Ambient 24 hours; Refrigerated: Unacceptable; Frozen: Unacceptable
Toll-like receptors (TLR) are tested independently by stimulation with TLR-specific ligands in a peripheral blood mononuclear cell (PBMC) culture. PBMC production of IL-1 beta, IL-6, and TNF alpha is determined by multiplex bead assay for TLR1-8. In addition, PBMC production of CXCL10 is determined for TLR3.
TLR-specific ligands include Pam3CSK4, a synthetic bacterial lipoprotein (TLR2-TLR1 ligand); zymosan cell wall particles from Saccharomyces cerevisiae (TLR6-TLR2 ligand); poly (I:C), a synthetic analog of dsRNA (TLR3 ligand); lipopolysaccharide (LPS) ultra-pure S. minnesota LPS (TLR4 ligand); flagellin purified from S. typhimurium (TLR5 ligand); and CL097 imidazoquinoline compound (TLR7-TLR8 ligand).
Compliance Statement B: For laboratory developed tests not using a RUO kit, and for FDA approved, cleared or 510(k) exempt assays with alterations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Results for TNF alpha, IL-1 beta, IL-6, and CXCL10 are reported as pg/mL. Interpretation comparing the patient results to the simultaneously collected client normal control and the laboratory normal control will be provided by an ARUP medical director.
Limitation: Defects in TLR3 associated with Herpes Simplex Encephalitis may not be detected in this assay based on the reported instance of a patient with compound heterozygous mutations in TLR3 leading to decreased cytokine production in response to Poly I:C in fibroblasts but not PBMCs1.
Proteins IRAK-4 and MyD88 play essential roles in TLR-mediated signaling. Defects in IRAK-4 and MyD88 result in compromised TLR signaling. Exceptions are , TLR3 and endosomal TLR4, which, are IRAK-4 and MyD88 independent.
1. Guo Y, Audry M, Ciancanelli M, Alsina L, Azevedo J, Herman M, et al. Herpes simplex virus encephalitis in a patient with complete TLR3 deficiency: TLR3 is otherwise redundant in protective immunity. J Exp Med. 2011;208(10):2083-98.
86353 x6; 83520 x3
|Component Test Code*||Component Chart Name||LOINC|
|0051589||Toll-Like Receptor Function|
- TLR Function