The Profile of Toll-like Receptor 2 (TLR2), TLR4 and Their Cytosolic Downstream Signaling Pathway in Common Variable Immunodeficiency (CVID) Patients.

Common variable immunodeficiency (CVID) is the most common clinical primary antibody deficiency, characterized by increased susceptibility to recurrent bacterial infections. Since Toll-like receptors (TLRs) play an important role in the maturation and differentiation of B-cells, TLRs' defect can be involved in the pathogenesis of CVID. Therefore, we evaluated the expression of TLR2 and TLR4 and their signaling pathway; also their association with autoimmunity, B-cell subtypes and response to pneumovax-23 were assessed in CVID patients. Sixteen CVID patients were enrolled in the study. Flow cytometry was used for assessing the protein expression of TLR2 and TLR4, and real-time PCR was used for gene expression of myeloid differentiation primary response 88 (MyD88) and toll interacting protein (Tollip). We found a higher protein expression of TLR2 in CVID patients which was associated with lower number of end stage B-cells and hyporesponse to pneumovax-23 vaccination. We showed a lower mRNA expression of MyD88 and an almost equal Tollip mRNA expression in CVID patients compared with controls. There was a profound association between MyD88 gene expression and autoimmunity in CVID patients. According to the presence of the lower number of end stage B-cells and poor vaccine response in CVID patients and their correlation with the higher expression of TLR2, we hypothesized that there is a functional defect in this receptor and/or its downstream in the peripheral blood mononuclear cells (PBMCs) of CVID patients.