Review Article
Shubhasree Banerjee; Kamel Hamzaoui; Anahid Safari; Afshin Borhani-Haghighi
Abstract
Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural ...
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Neuro-Behcet's disease (NBD) is a rare but potentially fatal manifestation of Behcet's disease. Common presentations of neuro-Behcet's disease are parenchymal (brainstem and hemispheric manifestations, meningoencephalitis, spinal cord lesions) and non-parenchymal (arterial occlusions, aneurysms, Dural sinus thrombosis). Cerebrospinal fluid (CSF) findings in parenchymal NBD usually show an inflammatory pattern with elevated cell count (usually high levels of polymorphonuclear leukocytes), high protein, and normal glucose levels, whereas the CSF findings in non-parenchymal NBD could be normal except for high opening pressure. Further investigation of CSF in parenchymal NBD has demonstrated elevated Natural killer T cells, high inflammatory chemokines, and cytokines such as Tumor Necrosis Factor-alpha (TNF- α), Interferon-gamma (IFN-γ), Interleukin (IL)12, IL-6, IL-17, IL-26, IL-15, Vascular endothelial growth factor (VEGF), Matrix metallopeptidase 9 (MMP-9), chemokine [C-X-C motif] ligand 8 (CXC-8) which indicate the role of both innate and adaptive immunity in this disease. Particularly, T helper type 1 (TH-1) and TH-17 pathways are implicated in the pathogenesis of this condition. Successful use of certain biologic agents such as TNF and IL-6 inhibitors in NBD further emphasizes the role of inflammatory cytokines in the immunopathogenesis of the disease. Drugs blocking the TH 17 pathway such as ustekinumab, secukinumab could also be applicable in the process. This review summarizes the detailed CSF findings in NBD, current understanding of the immunopathogenesis of NBD, and treatment of NBD with specific biologic agents based on our understanding of the disease pathogenesis.
Original Article
Samaneh Delavari; Mehri Ghafourian; Elham Rajaei; Karim Mowla; Ata Ghadiri
Abstract
Background: Rheumatoid arthritis (RA) is the most common rheumatoid disease of unknown etiology, determined by the articular cartilage destruction and bone loss. The hallmark of RA is the defect in immune tolerance. Regulatory T cells (Treg) play a critical role in the protection of peripheral tolerance. ...
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Background: Rheumatoid arthritis (RA) is the most common rheumatoid disease of unknown etiology, determined by the articular cartilage destruction and bone loss. The hallmark of RA is the defect in immune tolerance. Regulatory T cells (Treg) play a critical role in the protection of peripheral tolerance. Objective: To assess the percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients as compared with the healthy individuals. Methods: The number of CD4+/CD25+/high/CD127low/- Treg cells was assessed by multicolor flow cytometry. The clinical disease activity of RA patients was determined by disease activity score 28 (DAS-28). The correlations of DAS-28 and erythrocyte sedimentation rate (ESR) with Treg cells were evaluated. Results: The percentage of CD4+/CD25+/high/CD127low/- Treg cells in peripheral blood of RA patients significantly decreased as compared with the healthy individuals (P= 0.0002). The percentage of CD4+/CD25+/high/CD127low/- Treg cells negatively correlated with DAS-28 and ESR. Conclusion: This study concludes that the defect of Treg cells plays a vital role in the pathogenesis of this disease. Further studies are necessary to determine the role of Treg cells in the clinical course of rheumatoid arthritis.
Original Article
Chuling Li; Yaxiong Xu; Xianglin Luo; Fajian Chen
Abstract
Background: Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation by producing interleukin-4 (IL-4), IL-5, IL-9, and IL-13. IL-18 can promote T helper 2 cell (Th2) response by inducing IL-4, and IL-13 production from mast cells and basophils. However, the regulation of IL-18 on ILC2s remained ...
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Background: Group 2 innate lymphoid cells (ILC2s) promote allergic inflammation by producing interleukin-4 (IL-4), IL-5, IL-9, and IL-13. IL-18 can promote T helper 2 cell (Th2) response by inducing IL-4, and IL-13 production from mast cells and basophils. However, the regulation of IL-18 on ILC2s remained unknown. Objective: To investigate the regulatory role of IL-18 in inducing the type 2 innate lymphoid cells. Methods: Twenty patients with allergic rhinitis (AR) and 20 controls were enrolled. The mRNA and protein levels of IL-18 in serum, as well as the frequencies of ILC2 in peripheral blood mononuclear cells (PBMCs) were measured by real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. The ILC2s were sorted and the mRNA expression of IL-18 receptor in ILC2 was analyzed by real-time PCR. The effects of IL-18 on the proliferation and type 2 cytokine production were detected by tritiated thymidine incorporation test, real-time PCR, and ELISA, respectively. Results: The levels of IL-18 mRNA and protein were significantly higher in AR patients than in the controls (P<0.05). The frequency of ILC2 in peripheral blood was elevated in the AR patients than in the controls. After stimulation by IL-18 and house dust mite (HDM), the expression of IL-18 receptor (IL-18R) by ILC2 was significantly up-regulated. The tritiated thymidine incorporation results showed that IL-18 promoted the proliferation of ILC2 in a dose-dependent manner. IL-18 also induced the expression of IL-5 and IL-13 proteins by ILC2. Conclusion: Our results confirmed -for the first time- the effect of IL-18 in innate immunity, which was demonstrated by direct effect on the differentiation and function of ILC2.
Original Article
Zhangqiao Cai; Xuxia He; Jing Yang
Abstract
Background: Allergic asthma is believed to be a T helper 2 cell (Th2) preponderant response caused by airway hyper-responsiveness. Interleukin-35 (IL-35) is a newly discovered anti-inflammatory cytokine. Objective: To determine whether the expression of IL-35 is associated with type-2 inflammation in ...
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Background: Allergic asthma is believed to be a T helper 2 cell (Th2) preponderant response caused by airway hyper-responsiveness. Interleukin-35 (IL-35) is a newly discovered anti-inflammatory cytokine. Objective: To determine whether the expression of IL-35 is associated with type-2 inflammation in children with asthma exacerbations. Methods: Thirty children (6-12 years old) with acute allergic asthma and twenty healthy controls were enrolled. Sputum was collected from lower airways. IL-35 and type 2 cytokines expression from serum and sputum were measured at mRNA and protein level by real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The sampling and the test were repeated eight weeks after the asthma exacerbation. Results: At the time of exacerbation, IL-35 expression decreased significantly in induced sputum and serum than in the controls. The expression of IL-35 was negatively correlated with IL-4, IL-5 and IL-13 expression. The IL-35 from induced sputum increased significantly, whereas type-2 cytokines decreased significantly eight weeks after the exacerbation. Conclusion: Our results showed that decreased IL-35 was associated with type-2 cytokines in asthma exacerbations in children, suggesting that IL-35 may be a potential future drug target for asthma exacerbations.
Original Article
Yanni He; Qiaorong Yang; Tong Zhang; Yibin Zeng; Lingbo Du; Wuqing Wang
Abstract
Background: Acne is a common and chronic inflammatory dermatosis of sebaceous gland units of the human hair follicle. Acne is closely related to immune cytokines and cells including T helper 17cells (Th17 cells). Mis-regulated glycolipid metabolism also plays a vital role in the process. Objective: This ...
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Background: Acne is a common and chronic inflammatory dermatosis of sebaceous gland units of the human hair follicle. Acne is closely related to immune cytokines and cells including T helper 17cells (Th17 cells). Mis-regulated glycolipid metabolism also plays a vital role in the process. Objective: This investigation aimed to explore the role of IL-17 in signaling pathways controlling sebaceous gland lipoprotein metabolism in a rat model of acne. Methods: We generated the rat ear acne model, and investigated the pathological changes of acne skin tissue by histological analysis and the changes in the critical factors including DEFB1, GPR65, FADS1, and FADS2 by Western Blot in this model. Results: There were more Th17 cells in the rat ear acne model than in the control mice. The expression levels of DEFB1, GPR65, FADS1, FADS2 and MOGAT1 were significantly upregulated in serum and tissue from rat acne model, which could be concluded that the Th17 cells play a major role in the pathogenesis of acne based. Conclusion: Although acne is associated with immune effects and glycolipid metabolism, inhibition of IL-17 signaling pathway might be a novel way for acne therapy. Our findings also suggest a new strategy for targeted therapy of acne.
Original Article
Xueqin Wang; Yingying Gao; Xingyu Ge; Zhifeng Gu
Abstract
Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between ...
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Background: Pulmonary manifestations of systemic lupus erythematosus (SLE) are appearing in 4-5% of patients involving lung in almost half of the cases during the disease course. Objective: We compared the autoimmune pulmonary inflammation in the lung tissue of mice to determine the association between decreased expression levels of Forkhead Box J1 (FOXJ1) and the activation of the NF-κB pathway in autoimmune pulmonary inflammation of MRL/Lpr mice. Methods: The female BALB/c mice (n=6) and MRL/Lpr mice (n=30) were divided into 5 groups including a control group (BALB/c), and five MRL/Lpr mice groups (8W, 12W, 16W, 24W, and 32W). The infiltration of the inflammatory cells was determined in lung tissue by performing the histological analysis. The western blotting was used to examine the expression levels of the age-related FOXJ1, and p50 and p65 proteins in the lungs of MRL/Lpr mice. The expression levels of MMP2 and MMP9 were determined via immunohistochemistry and immunofluorescence. Results: There were severe infiltrates of lung cells with high levels of tracheal damage, perivascular injury and interstitial inflammatory cell infiltration when the MRL/Lpr mice from 16w to 32w comparing to the 8w old healthy MRL/Lpr mice in the control group (p <0.05). Moreover, the reduced expression levels of FOXJ1 were associated with the activation of the NF-κB pathway in interstitial lung disease of MRL/Lpr mice via the modulation of p50 and p65. In addition, the expression levels of MMP2 and MMP9 pro-inflammation factors increased in the lungs of the MRL/Lpr mice from 16w to 32w. Conclusions: The expression level of FOXJ1 might be an indicator of the degree of lung disease in lupus-prone mice.
Original Article
Heyam Awad; Ammar Sfaira; Yousef Abu Osba; Mohammad Shahin; Yousef Al- Asa'd; Nooredeen Isbeih; Maha Shomaf; Wasan Hayagneh
Abstract
Background: Primary Eosinophilic Colitis (PEC) is one of the rare eosinophilic gastrointestinal diseases with a poorly understood pathogenesis. Eosinophilic esophagitis (EE) is the most common and best-understood disease in this category. Activated mast cells (MCs) have a role to play in the tissue damage ...
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Background: Primary Eosinophilic Colitis (PEC) is one of the rare eosinophilic gastrointestinal diseases with a poorly understood pathogenesis. Eosinophilic esophagitis (EE) is the most common and best-understood disease in this category. Activated mast cells (MCs) have a role to play in the tissue damage in EE. It is not known if PEC shares this mechanism. Objective: This cross-sectional study aimed to investigate the number of MCs in PEC and to compare them with cases of secondary colonic tissue eosinophilia (TE) and normal colon. Methods: The study included 19 PEC cases, 47 cases of secondary tissue eosinophilia and 50 normal colon tissues. Histopathological slides of all cases were reviewed to confirm the diagnosis and count the number of eosinophils. Glass slides for all cases were stained for C-kit (CD117) to highlight and count the MCs. Results: The mean number of the MCs in normal controls was 9.7 MCs per HPF (SD= 4.6). The mean number of MCs in the PEC cases was 26.5 (SD=7.1) which was significantly higher than the normal counts (p-value <0.000). The mean number of MCs in the secondary TE group was 18.0 (SD=7.1), which was significantly higher than normal controls; p-value <0.000. Comparing MC counts in PEC and secondary TE also revealed a significant difference with a p-value of < 0.000. Conclusion: MCs in PEC are significantly higher than those in secondary TE and normal controls. This suggests the role of the MCs in the pathogenesis of Primary Eosinophilic Colitis.
Original Article
Sayed Mahdi Marashi; Shima Izadi; Seyed Reza Najafizadeh; Ahmad Nejati; Majid Teymoori-Rad; Shohreh Shahmahmoodi; Forough Golsaz-Shirazi; Fazel Shokri
Abstract
Background: Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. Objective: To explore the overall status of EBV, ...
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Background: Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. Objective: To explore the overall status of EBV, TLR7, TLR9, and IFN-α gene expression in 32 patients suffering from SLE and 32 healthy controls. Methods: Plasma and PBMCs were separated from fresh whole blood. To measure EBV DNA load and mRNA levels of IFN-a, TLR-7 and9 in PBMCs, molecular techniques were employed. The production of IFN-α, ds-DNA IgG antibody, and EBNA-1 IgG levels were also measured in plasma by ELISA. Results: SLE patients showed significantly higher EBV load (p=0.001) and transcriptional levels of TLR7 (p=0.0001), IFN-α (p=0.0001), and TLR9 (p=0.0001) than controls. Moreover, the plasma levels of IFN-α (p=0.0002) and EBNA-1specific IgG antibodies (p=0.01) were significantly higher in SLE patients. Conclusion: The results stressed on the potential role of EBV infection and TLRs in SLE patients although more research is needed to determine the global impact that EBV infection can have on immune signature in patients with SLE.
Original Article
Mohammad Asgharzadeh; Davoud Sanajou; Hossein Samadi Kafil; Mehdi Farhoudi; Daryoush Savadi Oskouei; Fatemeh Khaki-Khatibi; Fatemeh Ahmadi; Manouchehr Fadaee; Ali Vegari; Vahid Asgharzadeh; Jalil Rashedi; Behroz Mahdavi Poor; Pourya Gholizadeh
Abstract
Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes ...
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Background: Changes in the expression of cytokines as the result of the single nucleotide polymorphisms (SNPs), can affect the incidence of multiple sclerosis (MS). Objective: To investigate the relationship between the frequencies of interleukin-10 (IL-10)-1082 A/G (rs1800896) and CCR5-delta32 genotypes and susceptibility to MS in the Iranian Azari population. Methods: IL-10-1082 A/G SNP and the CCR5-delta32 were genotyped in 152 patients suffering from MS and 242 healthy non-relatives by allele specific-PCR and simple PCR methods, respectively. Results: The frequencies of AA (37.6%) and AG (55.9%) genotypes of IL-10-1082 were significantly high in the control (p = 0.021) and MS patients (p = 0.015), respectively, with no statistical difference between these groups. There was no significant difference in the CCR5 gene based on the possession of wild/wild and wild/del32 genotypes between MS patients and the control group. The del32/del32 genotype was not seen in any of the investigated groups. Tobacco (cigarettes and hookahs) consumption was higher among the MS patients (p=0.004), and this has the potential to raise the risk of MS in both the individuals and their family. However, it had no significant relation with the frequency of different genotypes of the IL-10-1082 and the CCR5. Conclusion: Our finding conclude on possible role of AA genotype of IL-10 -1082 as a protective factor in MS.
Original Article
Mehrdad Nasrollahzadeh Sabet; Navid Nasrabadi; Zahra Jalili; Bahram Pakzad; Saeideh Davar; Naeim Ehtesham; Sima Jafarpour; Meysam Mosallaei; Emran Esmaeilzadeh
Abstract
Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation ...
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Background: Rheumatoid arthritis (RA) is a complex systemic autoimmune disorder with multifactorial nature. Numerous previous studies have shown that several genes are involved in the pathogenesis and increased risk of RA. The Nod-like receptor pyrin domain containing 3 (NLRP3) is involved in the regulation of innate immunity and its upregulation has previously been reported in RA. Objective: To evaluate the correlation between 3 functional polymorphisms of NLRP3 and its gene expression and RA risk. Method: One hundred and fourteen patients with RA and 120 healthy participants were recruited to this case-control study. Genotyping of rs4612666 (intronic variant), rs10754558 (3UTR variant), and rs6672995 (downstream variant) were performed applying the real‑time polymerase chain reaction high‑resolution melting (HRM) method. Results: Based on logistic regression analysis, subjects with CC genotype and C allele in rs4612666 had increased risk of RA (OR for CC genotype= 3.10; 95%CI [1.78-8.26]/ OR for C allele= 2.00; 95%CI [1.45-3.10]). Furthermore, in the patient groups, there was a significant relationship between the concentration of C-reactive protein (CRP) and rs4612666 and rs10754558 polymorphism (p < 0.05). Besides, our results revealed no significant association between the genotype and allele frequency of rs10754558 and rs6672995 and the risk of RA (P> 0.05). Conclusion: Our findings propose a significant association between rs4612666 polymorphism and increased risk of RA in the Iranian population. Moreover, rs4612666 and rs10754558 were correlated with disease activity.
Original Article
QingXiao Su; LiJun Jiang; Jia Chai; ZhiYan Dou; ZanHua Rong; Xue Zhao; Bo Yu; YuXue Wang; XinLiang Wang
Abstract
Background: Purpuric nephritis is the most common secondary glomerular disease in childhood. Its prevalence in children has been steadily rising in recent years. Objective: To explore the characteristics and pathogenesis of changes in peripheral blood lymphocyte subsets and immune function in children ...
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Background: Purpuric nephritis is the most common secondary glomerular disease in childhood. Its prevalence in children has been steadily rising in recent years. Objective: To explore the characteristics and pathogenesis of changes in peripheral blood lymphocyte subsets and immune function in children with Henoch-Schonlein purpura nephritis. Methods: The study included 104 children with Henoch-Schonlein purpura, divided into nephritis (HSPN) group (68 cases) and non-nephritis (NHSPN) group (36 cases), and 15 normal children. The rate-scatter turbidimetric method was utilized to determine the immunoglobulins IgA, IgG, IgM, C3 and C4, and the flow cytometry technique was employed to detect the levels of lymphocyte subsets including CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, NK, etc. Results: Compared with the control group, the CD3+, CD4+, CD8+ and NK cell levels of peripheral blood mononuclear cells significantly decreased (p <0.05), and the CD19+ level significantly elevated (p <0.05) in the HSPN group and the NHSPN group whereas the HSPN group had a more significant change than the NHSPN group (p <0.05). Compared with the control group, the serum immunoglobulin IgA and IgG of the HSPN group and the NHSPN group significantly increased, and the IgM, C3, and C4 significantly decreased (p <0.05); while the HSPN group had a more significant change than the NHSPN group (p <0.05). Conclusion: Immune dysfunction in children with HSPN is specifically manifested as low cellular immune function, which leads to increased secretion of inflammatory mediators, activates B cells, and further increases the secretion of immunoglobulins, leading to the occurrence of small vasculitis.
