Objectives: We evaluate the frequency and functional response of innate immune cells in peripheral blood (PB) from patients with common variable immunodeficiency (CVID) and healthy controls upon activation with agonists of the Toll-like receptors (TLR) TLR2, TLR4, and TLR9. In addition, several nonsynonymous single nucleotide polymorphisms (SNPs) within these TLR genes were examined.

Methods: Flow cytometry was used to perform immunophenotyping and evaluate the expression of cell surface markers. Levels of cytokines in the culture supernatants were evaluated using cytometric bead array technology. SNPs in the TLR genes were evaluated from genomic DNA using different sequencing techniques.

Results: Our results demonstrate that the frequency of CD1d-restricted TCR invariant natural killer T cells in PB was significantly reduced in the patients with CVID. A marked, though not significant, reduction in absolute numbers of plasmacytoid dendritic cells and natural killer cells was also observed in these patients. Interestingly, CD80 and CD86 expression on innate cells upon stimulation with TLR ligands was not altered in the patients although 3 of them exhibited low baseline levels of these surface molecules on monocytes compared to healthy controls. We also observed a significant increase in TNF-α levels in supernatants of PB mononuclear cells from CVID patients after stimulation with lipopolysaccharide. Finally, no association was found between the presence of nonsynonymous SNPs within the TLR genes and the clinical presentation of CVID.

Conclusions: Taken together, our study demonstrates than innate immune responses are disturbed in some CVID patients and prompts the evaluation of innate immunity genes as candidates to explain the CVID clinical phenotype.

Key words: Common variable immunodeficiency. Innate immunity. Lipoteichoic acid. Lipopolysaccharide. CpG oligodeoxynucleotides.