Author/Authors :
Sharifi, Laleh Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Aghamohammadi, Asghar Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Rezaei, Nima Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Yazdani, Reza Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Mahmoudi, Mahdi Rheumatology Research Center - Tehran University of Medical Sciences, Tehran , Amiri, Mohammad Mehdi Department of Immunology - School of Public Health - Tehran University of Medical Sciences, Tehran , Masoumi, Farimah Department of Immunology - School of Medicine - Tehran University of Medical Sciences, Tehran , Bokaie, Saied Department of Epidemiology - Faculty of Veterinary Medicine - University of Tehran, Tehran , Tavasolian, Parsova Department of Immunology - School of Medicine - Tehran University of Medical Sciences, Tehran , Sanaei, Roozbeh Department of Immunology - Iran University of Medical Sciences, Tehran , Moshiri, Mona Department of Microbiology - School of Public Health - Tehran University of Medical Sciences, Tehran , Tavakolinia, Naeimeh Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Alinia, Tina Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran , Azizi, Gholamreza Non-Communicable Diseases Research Center - Alborz University of Medical Sciences, Karaj , Mirshafiey, Abbas Research Center for Immunodeficiencies - Pediatrics Center of Excellence - Children’s Medical Center - Tehran University of Medical Sciences, Tehran
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.
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)
