Addressing diagnostic challenges in primary immunodeficiencies: Laboratory evaluation of Toll-like receptor- and NF-κB-mediated immune responses

Toll-like receptors (TLRs) play an important role in immunity and mediate their actions via multiple signaling pathways, in particular, the nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-kappa B) pathway. Rare inherited defects of TLR- and NF-kappa B-dependent responses have recently been recognized. These primary immunodeficiencies predispose children to life-threatening infections and often remain undiagnosed. Establishing a sensitive, specific, cost-effective and simple method for diagnosis is therefore important. In this article, we review the known defects of TLR- and NF-kappa B-mediated pathways and the assays that can be used to screen for such defects.