Iranian Journal of Immunology最新文献

Background: The relationship between genetic polymorphism and postoperative pain and the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is not fully understood.

Objective: To examine whether lncRNA-GAS5 and its promoter region rs145204276 polymorphism can predict postoperative pain and prognosis of the patients with HCC undergoing hepatectomy.

Methods: Seventy patients with HCC undergoing hepatectomy were enrolled. The lncRNA-GAS5 levels in CD4+ T cells from peripheral blood mononuclear cells (PBMC-CD4+ T cells) and tumor tissues were measured by qRT-PCR. Genotyping analysis of rs145204276 was performed using the TaqMan platform. PBMC-CD4+ T cells were isolated and the cytokine levels in helper T (Th) cells were determined by flow cytometry. Patients with Ins/Ins genotype carrying the rs145204276 polymorphism were allocated into the Ins group, and others were allocated into the Del group.

Results: The lncRNA-GAS5 level decreased significantly in PBMC-CD4+ T cells and tumor tissues compared with the healthy controls and corresponding adjacent non-tumor tissues. The patients with Del/Del genotype showed significantly higher lncRNA-GAS5 expression in PBMC-CD4+ T cells, lower postoperative pain scores, and better overall survival. LncRNA-GAS5 expression in PBMC-CD4+ T cells was negatively associated with IL-6, IL-17, and the RORγT/CD3 ratio (an indicator of Th17 polarization).

Conclusion: LncRNA-GAS5 expression and its promoter region rs145204276 polymorphism are prognostic biomarkers that can predict postoperative pain of patients with HCC undergoing hepatectomy.

Background: Natural killer (NK) cells are classified as innate immune cells which can directly recognize and kill tumor cells without antigen sensitization. NK cell-based adoptive immunotherapy for blood malignancies has attracted more attention in recent years.

Objective: To analyze different NK cell subsets in the peripheral blood and bone marrow (BM) of patients with multiple myeloma (MM).

Methods: Using flow cytometry we analyzed: (i) the distribution of distinct NK cell subpopulations (i.e. CD16low CD56low, CD16pos CD56high, CD16neg CD56high, CD16high CD56low, CD16neg CD56low, CD16low CD56low CD38pos) in the BM from MM patients at distinct disease stages. (ii) the expression of NKG2D, DNAM-1 and NKp30, and (iii) the expression of CD107a in CD16low CD56low CD38pos and CD16low CD56low CD38neg NK cells subsets.

Results: CD16low CD56low CD38pos was the dominant subset in BM from patients with MM at the CR stage with a decreased expression of NKp30. CD16low CD56low CD38pos subset showed a higher proportion of CD107a expression compared to CD16low CD56low CD38neg cells. In vitro experiments indicated that the CD16low CD56low CD38pos NK cell subset possesses more cytotoxicity than CD16low CD56low CD38neg NK cells.

Conclusion: Our data suggest that CD16low CD56low CD38pos NK cells may reflect as an effector population with the potential therapeutic target in patients with MM. This group of cells may be useful for adoptive immunotherapy in MM in the future.

Background: Asthma is a heterogeneous disorder of the airways related to inflammation; it affects millions of people worldwide. Due to the side effects of inhaled corticosteroids, researchers focused on the therapeutic effects of compounds derived from natural products.

Objective: To investigate the therapeutic benefits of Narirutin a valuable flavonoid in Citri Reticulatae Pericarpium for asthma.

Methods: Narirutin was extracted using the enzyme-assisted method with the L9 (34) orthogonal array to optimize the temperatures, pH, and reaction time. The mechanism of action of Narirutin was investigated via ELISA, flow cytometry, and Western blot analysis in vivo.

Results: Narirutin suppressed inflammatory cell infiltration in the lung tissue and decreased IgE and IgG1 levels in serum in vivo. It can also alleviate interleukin (IL)-4, IL-5, and interferon-γ concentrations in bronchoalveolar lavage fluid in mice. Moreover, it increased the ratio of CD4+/CD8+ T cells. Additionally, Narirutin significantly suppressed p-ERK1/2 and p-JNK expression in the MAPK signaling pathway.

Conclusion: Narirutin affects the Th1/Th2 imbalance through the p-ERK and p-JNK suppression in the MAPK signaling pathway.

Background: Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2).

Objectives: To compare the antibody response of healthy individuals vaccinated with either the AstraZeneca (ChAdOx1 nCoV-19) or the Sinopharm (BBIBP-CorV) vaccine, in those who had no prior infection with SARS-CoV-2.

Methods: Thirty seven participants were included, of which 17 were administered the AstraZeneca (ChAdOx1 nCoV-19) vaccine, while 20 were given the Sinopharm (BBIBP-CorV) vaccine. SARS-CoV-2 neutralizing antibody and anti-receptor-binding domain (RBD) IgG levels were checked 4 weeks after giving the first and the second dose of either vaccine using the enzyme-linked immunosorbent assay (ELISA) technique.

Results: The AstraZeneca (ChAdOx1 nCoV-19) vaccine exhibited a higher levels of anti-(RBD) IgG compared with the Sinopharm (BBIBP-CorV) in both the first (14.51 μg/ml vs. 1.160 μg/ml) and the second (46.68 μg/ml vs. 11.43 μg/ml) doses. About neutralizing Abs, the titer of the antibody was higher in the AstraZeneca (ChAdOx1 nCoV-19) recipients than in the Sinopharm (BBIBP-CorV) subjects after the first (7.77 μg/ml vs. 1.79 μg/ml, p < 0.0001) and the second dose (10. 36 μg/ml vs. 4.88 μg/ml, p < 0.0001).

Conclusions: Recipients vaccinated with two doses of the AstraZeneca (ChAdOx1 nCoV-19) had superior quantitative antibody levels than Sinopharm (BBIBP-CorV)-vaccinated subjects. These data suggest that a booster dose may be needed for the Sinopharm (BBIBP-CorV) recipients, to control the COVID-19 pandemic.

Background: Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD.

Objectives: To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci.

Methods: A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method.

Results: Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis.

Conclusions: Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.

Background: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however, the mechanism is yet little understood.

Objective: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms.

Materials and methods: Serum vitamin D, Interferon-γ (IFN-γ) and Interleukin (IL)-17 levels of the patients with UC were quantified using enzyme-linked immunosorbent assay (ELISA). Long non-coding RNAs (lncRNAs) levels were determined by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were collected from healthy control subjects, stimulated with CD4+ T lymphocytes or helper T cells 17(Th17) differentiation conditions, and then exposed to calcitriol (vitamin D active form) or certain lentiviral treatment, followed by subsequent molecular level testing. For in vivo assay, mice were given 3% dextran sulfate sodium (DSS) to induce colitis.

Results: Compared with the control group, vitamin D levels in the UCs were statistically lower, and there was a negative correlation between IL-17 and vitamin D in the UCs. The lncRNA OIP5-AS1 could decrease under calcitriol treatment in both CD4+ T cells and Th17 differentiation. The lncRNA OIP5-AS1 was a microRNA (miR)-26a-5p sponge and therefore modulated the Th17 cells and IL-6 expression. The lncRNA OIP5-AS1/miR-26a-5p/IL-6 axis mediated the regulation of calcitriol-induced Th17 differentiation. Calcitriol had therapeutic effects on the UC mouse models by regulating the lncRNA OIP5-AS1 related pathway.

Conclusion: Vitamin D might have anti-inflammatory potential in the treatment of the UC.

Background: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases.

Objectives: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics.

Methods: Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed.

Results: The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity.

Conclusions: FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.

Background: Various factors contribute to the pathogenesis of Multiple Sclerosis (MS), one of which is Fibroblast Growth Factor 2 (FGF2). The function of FGF2 is pleiotropic. The investigation of the role of this factor in the myelination has produced conflicting results.

Objective: To investigate the serum levels of FGF2 in patients with MS.

Subjects and methods: Eighty patients with MS and eighty healthy volunteers with no history of inflammation or demyelinating disorders were included, and serum samples were collected to evaluate serum levels of FGF2 using the ELISA technique. Both groups had the same age and gender distribution. For analysis, the Mann-Whitney U test was used.

Results: Patients with MS had considerably greater serum FGF2 levels than the control group (p = 0.005). There was no difference between the FGF2 level in men and women.

Conclusion: Our data indicate that FGF2 levels may be related to the susceptibility of Iranian patients with MS. Further studies are required to analyze the involvement of FGF2 in enhancing the inflammatory process in MS.

Follicular helper T (TFH) cells are a subset of effector CD4+ T cells that support the differentiation of antigen-specific B cells in the germinal center. TFH cells are distinct from other established CD4+ T cell subsets and possess a list of transcription factors, including BCL6, IRF4, c-Maf, Batf, NFAT1-2, and STAT3. The mentioned factors direct several activities such as cell differentiation, migration to the follicles, cell-to-cell interaction, as well as cell programming. Given that TFH cells are essential for the germinal center formation, affinity maturation and the development of most high-affinity antibodies. TFH cells may play crucial roles in different pathologic conditions, particularly autoimmune diseases. However, the mechanisms that cause functional differences of TFH cell responses are not exactly defined. In this review first the immunological profile of TFH cells will be discussed then attempts will be made to give a broad picture on the role of this key subset of T cells in autoimmune diseases.