scholarly journals Serum Levels of IL-33 and Correlation with IL-4, IL-17A, and Hypergammaglobulinemia in Patients with Autoimmune Hepatitis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ma Liang ◽  
Zhang Liwen ◽  
Zhuang Yun ◽  
Ding Yanbo ◽  
Chen Jianping

This study investigated the role of IL-33 in the pathogenesis of autoimmune hepatitis (AIH). The levels of IL-33/sST2 and Th1/Th2/Th17-type cytokines were determined by enzyme-linked immunosorbent assay in serum samples obtained from 30 AIH patients and 20 healthy controls (HCs). In addition, a murine model of experimental AIH (EAIH) was established to investigate the role of IL-33 in disease progression. The serum levels of IL-33, sST2, Th17 cytokines (IL-17A), Th1 cytokines (IFN-γ, TNF-α), and Th2 cytokines (IL-4) were significantly elevated in AIH patients compared to HCs. Following immunosuppression therapy, serum levels of IL-33 and sST2 were significantly decreased. Additionally, the serum levels of IL-33 in AIH patients were correlated positively with markers of hypergammaglobulinemia (IgG, IgM, and IgA) and liver injury (γ-GT/ALP). Also, the serum levels of IL-33 in AIH patients were correlated positively with proinflammatory cytokine levels (IL-17A and IL-4). Interestingly, treatment of EAIH mice with a specific IL-33 neutralizing antibody significantly reversed the increasing trend in serum ALT/AST and inhibited the production of the type 2 (IL-4) and type 17 cytokines (IL-17) but not the type 1 cytokine (IFN-γ). Our findings highlight the possible role of the IL-33/sST2 axis in the progression of AIH, opening a new door for developing a novel therapeutic strategy for AIH.

2011 ◽  
Vol 3 ◽  
pp. BIC.S7154 ◽  
Author(s):  
Veyis Itik ◽  
Ozgur Kemik ◽  
Ahu Kemik ◽  
A. Cumhur Dulger ◽  
Aziz Sümer ◽  
...  

Aims and background YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. Methods Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population ( P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer ( P < 0.01). Conclusions YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment.


2021 ◽  
Vol 9 (A) ◽  
pp. 741-747
Author(s):  
Qudus W. Jamal ◽  
Ghassaq Alubaidi ◽  
Yasmin Humadi

BACKGROUND: Cytokines are inflammatory mediators that regulate multiple processes potentially implicated in inflammation and autoimmunity. AIM: This study aimed to investigate the levels of circulating interleukin (IL)-35, IL-36, and IL-35/IL-36 ratio in Juvenile Idiopathic Arthritis (JIA) patients. METHODS: Fifty-one patients categorized based on the International League of Associations for Rheumatology classification criteria were enrolled, along with 46 healthy controls. Disease activity assessment was conducted according to the Juvenile Arthritis Disease Activity Score (JADAS-27) system. Serum cytokine levels were determined using the sandwich enzyme-linked immunosorbent assay. RESULTS: Compared to controls, the serum levels of IL-36 were significantly higher among JIA children (p = 0.002), and serum IL-35 levels and the IL-35/IL-36 ratio were significantly lower in the patients (p = 0.002, p < 0.001, respectively). Furthermore, the IL-35/IL-36 serum ratio, but not the absolute IL levels, correlated positively with the JADAS-27, giving a good indication of the disease outcome. Further, the IL-35/IL-36 serum ratio showed higher sensitivity and specificity compared to the absolute cytokine levels. CONCLUSION: A significant change in the circulating IL-35 and IL-36 levels and an imbalance in the IL35/IL36 ratio occur in JIA. This study is a novel attempt to explore the role of IL-35 and IL-36 in JIA; further studies are required to support our results. The IL-35/Il-36 ratio is a promising immunological marker to predict, diagnose, and monitor JIA.


Author(s):  
Tatsuro Saruga ◽  
Tadaatsu Imaizumi ◽  
Shogo Kawaguchi ◽  
Kazuhiko Seya ◽  
Tomoh Matsumiya ◽  
...  

AbstractC-X-C motif chemokine 10 (CXCL10) is an inflammatory chemokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Melanoma differentiation-associated gene 5 (MDA5) is an RNA helicase that plays a role in innate immune and inflammatory reactions. The details of the regulatory mechanisms of CXCL10 production and the precise role of MDA5 in RA synovitis have not been fully elucidated. The aim of this study was to examine the role of MDA5 in regulating CXCL10 expression in cultured human rheumatoid fibroblast-like synoviocytes (RFLS). RFLS was stimulated with Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA mimetic. Expression of interferon beta (IFN-β), MDA5, and CXCL10 was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay. A neutralizing antibody of IFN-β and siRNA-mediated MDA5 knockdown were used to determine the role of these molecules in regulating CXCL10 expression downstream of TLR3 signaling in RFLS. Poly I:C induced IFN-β, MDA5, and CXCL10 expression in a concentration- and time-dependent manner. IFN-β neutralizing antibody suppressed the expression of MDA5 and CXCL10, and knockdown of MDA5 decreased a part of CXCL10 expression (p < 0.001). The TLR3/IFN-β/CXCL10 axis may play a crucial role in the inflammatory responses in RA synovium, and MDA5 may be partially involved in this axis.


Author(s):  
Rahin Sh Hamad ◽  
Bushra H. Shnawa ◽  
Shereen J. Al-Ali

Colorectal cancer (CRC) is classified as one of the most prevalent cancer types worldwide, with high morbidity and mortality rates. Patients of CRC have been shown to express a detectable cytokine in serum which contributes to cancer pathogenesis. Therefore, the serum interleukin 10 (IL-10) level in CRC patients was investigated in this study. Patients' medical records with CRC admitted to the Rizgary and Nanakali hospitals, Erbil, Iraq was analyzed as the study group compared to the healthy volunteers' control group. Seventy-one serum samples were collected, thirty-one from diagnosed CRC patients and forty from healthy controls. The concentrations of IL-10 in the sera were assessed by enzyme-linked immunosorbent assay (ELISA). The present finding showed that IL-10 Was significantly elevated in CRC patients' sera compared to the control group, suggesting confirmation of its usefulness for detecting CRC patients' prognosis. A non-significant Pearson correlation was detected between IL-10 serum levels and the CRC group's age, gender, and body mass index. Herein is the first study on the evaluation of IL-10 levels in CRC patients in Kurdistan, Iraq.


2021 ◽  
Author(s):  
Nasamon Wanlapakorn ◽  
Nungruthai Suntronwong ◽  
Harit Phowatthanasathian ◽  
Ritthideach Yorsang ◽  
Thanunrat Thongmee ◽  
...  

Abstract Limited data are available on the responses to heterologous vaccine regimens for SARS-CoV-2, especially among countries using inactivated and adenoviral-vectored vaccines. A total of 77 participants who received heterologous prime/booster-inactivated COVID-19 vaccine and adenoviral-vectored vaccine were enrolled in our study. There were two comparison groups vaccinated with the homologous CoronaVac (N = 79) and AZD1222 (N = 80) regimen. All sera samples were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG using a chemiluminescent microparticle immunoassay (CMIA). The neutralizing activity in a subset of serum samples was tested against the original Wuhan strain and variants of concern, B.1.1.7 and B.1.351, using an enzyme-linked immunosorbent assay (ELISA)-based surrogate virus neutralization test (sVNT). The CoronaVac followed by the AZD1222 vaccine induced higher levels of spike RBD-specific IgG than that of two-dose CoronaVac or AZD1222 vaccines (p < 0.001). Sera samples of the CoronaVac/AZD1222 vaccine recipients elicited higher neutralizing antibody activity against the original Wuhan and the B.1.351 strain than in the recipients of the two-dose CoronaVac or AZD1222. Following the inactivated CoronaVac/adenoviral-vectored (AZD1222) vaccination administered 14–72 days apart, participants receiving the heterologous vaccine regimen had higher spike RBD-specific IgG and neutralizing activities than the homologous CoronaVac vaccine recipients.


2005 ◽  
Vol 79 (23) ◽  
pp. 14804-14814 ◽  
Author(s):  
Jason Hammonds ◽  
Xuemin Chen ◽  
Timothy Fouts ◽  
Anthony DeVico ◽  
David Montefiori ◽  
...  

ABSTRACT A major challenge for the development of an effective HIV vaccine is to elicit neutralizing antibodies against a broad array of primary isolates. Monomeric gp120-based vaccine approaches have not been successful in inducing this type of response, prompting a number of approaches designed to recreate the native glycoprotein complex that exists on the viral membrane. Gag-Env pseudovirions are noninfectious viruslike particles that recreate the native envelope glycoprotein structure and have the potential to generate neutralizing antibody responses against primary isolates. In this study, an inducible cell line was created in order to generate Gag-Env pseudovirions for examination of neutralizing antibody responses in guinea pigs. Unadjuvanted pseudovirions generated relatively weak anti-gp120 responses, while the use of a block copolymer water-in-oil emulsion or aluminum hydroxide combined with CpG oligodeoxynucleotides resulted in high levels of antibodies that bind to gp120. Sera from immunized animals neutralized a panel of human immunodeficiency virus (HIV) type 1 primary isolate viruses at titers that were significantly higher than that of the corresponding monomeric gp120 protein. Interpretation of these results was complicated by the occurrence of neutralizing antibodies directed against cellular (non-envelope protein) components of the pseudovirion. However, a major component of the pseudovirion-elicited antibody response was directed specifically against the HIV envelope. These results provide support for the role of pseudovirion-based vaccines in generating neutralizing antibodies against primary isolates of HIV and highlight the potential confounding role of antibodies directed at non-envelope cell surface components.


2007 ◽  
Vol 82 (2) ◽  
pp. 638-651 ◽  
Author(s):  
Yun Li ◽  
Bradley Cleveland ◽  
Igor Klots ◽  
Bruce Travis ◽  
Barbra A. Richardson ◽  
...  

ABSTRACT Glycans on human immunodeficiency virus (HIV) envelope protein play an important role in infection and evasion from host immune responses. To examine the role of specific glycans, we introduced single or multiple mutations into potential N-linked glycosylation sites in hypervariable regions (V1 to V3) of the env gene of HIV type 1 (HIV-1) 89.6. Three mutants tested showed enhanced sensitivity to soluble CD4. Mutant N7 (N197Q) in the carboxy-terminal stem of the V2 loop showed the most pronounced increase in sensitivity to broadly neutralizing antibodies (NtAbs), including those targeting the CD4-binding site (IgG1b12) and the V3 loop (447-52D). This mutant is also sensitive to CD4-induced NtAb 17b in the absence of CD4. Unlike the wild-type (WT) Env, mutant N7 mediates CD4-independent infection in U87-CXCR4 cells. To study the immunogenicity of mutant Env, we immunized pig-tailed macaques with recombinant vaccinia viruses, one expressing SIVmac239 Gag-Pol and the other expressing HIV-1 89.6 Env gp160 in WT or mutant forms. Animals were boosted 14 to 16 months later with simian immunodeficiency virus gag DNA and the cognate gp140 protein before intrarectal challenge with SHIV89.6P-MN. Day-of-challenge sera from animals immunized with mutant N7 Env had significantly higher and broader neutralizing activities than sera from WT Env-immunized animals. Neutralizing activity was observed against SHIV89.6, SHIV89.6P-MN, HIV-1 SF162, and a panel of subtype B primary isolates. Compared to control animals, immunized animals showed significant reduction of plasma viral load and increased survival after challenge, which correlated with prechallenge NtAb titers. These results indicate the potential advantages for glycan modification in vaccine design, although the role of specific glycans requires further examination.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Massimiliano Castellazzi ◽  
Simone Patergnani ◽  
Mariapina Donadio ◽  
Carlotta Giorgi ◽  
Massimo Bonora ◽  
...  

AbstractDementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer’s disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with “mixed” dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline.


2018 ◽  
Vol 38 (6) ◽  
pp. 1203-1206
Author(s):  
Vivien M. Morikawa ◽  
Maysa Pellizzaro ◽  
Igor A.D. Paploski ◽  
Mariana Kikuti ◽  
Maria C.C.S.H. Lara ◽  
...  

ABSTRACT: Bluetongue (BT) is an infectious and non-contagious disease of compulsory notification which may affect domestic and wild ruminants, transmitted by Culicoides spp. midges. Despite the high morbidity and mortality in sheep, role of wild animals in the BT cycle remains unclear. Caprine arthritis-encephalitis (CAE) and Maedi-Visna virus (MVV) have been reportedly found in goats and sheep, but not described in wildlife species. Accordingly, serum samples from 17 captive Barbary sheep (Ammotragus lervia) from Curitiba zoo, southern Brazil, were tested for bluetongue, caprine arthritis-encephalitis (CAE) and Maedi-Visna viruses by agar gel immunodiffusion (AGID) and enzyme linked immunosorbent assay (ELISA). Antibodies for bluetongue were observed in 6/17 (35.3%) Barbary sheep by AGID test and in 7/17 (41.2%) by ELISA. All samples were negative for the presence of antibodies against caprine arthritis-encephalitis (CAE) and Maedi-Visna viruses. These findings indicate that Barbary sheep may be infected by bluetongue virus and act as wildlife reservoir in both captive and free-range environments.


Cartilage ◽  
2020 ◽  
pp. 194760352096116
Author(s):  
Amin Safa ◽  
Abolfazl Bagherifard ◽  
Hamadalla Hadi Al-Baseesee ◽  
Azade Amini Kadijani ◽  
Hooman Yahyazadeh ◽  
...  

Objective The identification of early-stage osteoarthritis (OA) is crucial for the deceleration of its progression; however, no reliable biomarker is available for this purpose. The current study aimed to determine the role of serum calprotectin in the detection of early-stage knee OA. Design In a case-control study, serum samples were collected from 84 patients with primary bilateral knee OA and 52 healthy controls. The radiographic grading of knee OA was performed using the Kellgren-Lawrence classification system. Serum concentrations of calprotectin were measured using an enzyme-linked immunosorbent assay. Results The mean serum calprotectin level was 2908 ± 2516 ng/mL in OA patients and 901 ± 875 ng/mL in healthy control subjects ( P < 0.001). Mean serum calprotectin levels were significantly higher in the lower stages of OA: 3740 ± 2728 ng/mL in OA grade I, 3100 ± 2084 ng/mL in OA grade II, 2246 ± 1418 ng/mL in OA grade III, and 2035 ± 765 ng/mL in OA grade IV ( P = 0.047). Serum calprotectin levels were significantly higher in patients with a disease duration <42 months compared with those with a disease duration >42 months ( P = 0.043). Conclusion Serum calprotectin level increases significantly in the early stages of OA and shows a reverse association with disease severity. Therefore, it could be suggested as a promising blood-based marker for early-stage knee OA.


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