Evaluation of the TLR negative regulatory network in CVID patients

• Published in: Genes and immunity Vol. 20; no. 3; pp. 198 - 206
• Main Authors: Sanaei, Roozbeh, Rezaei, Nima, Aghamohammadi, Asghar, Delbandi, Ali-Akbar, Teimourian, Shahram, Yazdani, Reza, Tavasolian, Parsova, Kiaee, Fatemeh, Tajik, Nader
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2019; Nature Publishing Group
• Subjects: 13/106; 13/21; 45; 45/77; 631/208/199; 631/208/200; 631/250/249/2512; 631/250/262/2106/2108; Agammaglobulinemia; Age; Arthritis; Autoimmunity; B cells; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cellular signal transduction; Common variable immunodeficiency; CpG islands; Cytokines; Down-regulation; Enzyme-linked immunosorbent assay; Gene Expression; Human Genetics; Hypogammaglobulinemia; Immune system; Immunologic deficiency syndromes; Immunology; Infection; Inflammation; Kinases; Leukocytes (mononuclear); Ligands; Lipopolysaccharides; Lymphadenopathy; Lymphatic diseases; Medical research; Mitogens; Oligonucleotides; Pathogenesis; Patients; Peripheral blood mononuclear cells; Polymerase chain reaction; Primary immunodeficiencies; Recurrence (Disease); Statistical analysis; TLR4 protein; TLR9 protein; Toll-like receptors; Transcription; Tumor necrosis factor; Tumor necrosis factor-α; α-Interferon
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/s41435-018-0022-3

Common variable immunodeficiency (CVID), a clinically symptomatic primary immunodeficiency disease (PID), is characterized by hypogammaglobulinemia leading to recurrent infections and various complications. Recently, some defects in the signaling of TLRs have been identified in CVID patients which led us to investigate the expression of TLR4 and 9 negative regulatory molecules and their upregulation status following their activation. Using TaqMan real-time PCR, SOCS1 , TNFAIP3 , RFN216 , and IRAK-M transcripts among peripheral blood mononuclear cells (PBMCs) were measured with/without TLR4 and 9 activations. TLR4 and 9 were activated by lipopolysaccharide (LPS) and unmethylated CpG-oligodeoxynucleotide (CpG-ODN), respectively. Production of IFN-α and TNF-α cytokines, as a part of the functional response of mentioned TLRs, was also measured using ELISA. Deficient transcripts of IRAK-M and TNFAIP3 in unstimulated PBMCs and lower production of TNF-α and IFN-α after treatments were observed. Upregulation of RFN216 and TNFAIP3 after TLR9 activation was abnormal compared to healthy individuals. Significant correlations were found between abnormal IRAK-M and TNFAIP3 transcripts, and lymphadenopathy and inflammatory scenarios in patients, respectively. It seems that the transcriptional status of some negative regulatory molecules is disturbed in CVID patients, and this could be caused by the underlying pathogenesis of CVID and could involve complications like autoimmunity and inflammatory responses.