The Profile of Toll-like Receptor 2 (TLR2), TLR4 and Their Cytosolic Downstream Signaling Pathway in Common Variable Immunodeficiency (CVID) Patients
-
Laleh Sharifi
,
Asghar Aghamohammadi
,
Nima Rezaei
,
Reza Yazdani
,
Mahdi Mahmoudi
,
Mohammad Mehdi Amiri
,
Farimah Masoumi
,
Saied Bokaie
,
Parsova Tavasolian
,
Rouzbeh Sanaei
,
Mona Moshiri
,
Naeimeh Tavakolinia
,
Tina Alinia
,
Gholamreza Azizi
,
Abbas Mirshafiey
Abstract
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.
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| Files | ||
| Issue | Vol 17, No 2 (2018) | |
| Section | Original Article(s) | |
| Keywords | ||
| Common variable immunodeficiency (CVID) Myeloid differentiation primary response 88 (MyD88) Toll-like receptor 2 (TLR2) Toll-like receptor 4 (TLR4) Toll interacting protein (Tollip) | ||
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