scholarly journals IMMMUNE MEDIATORS IN IDIOPATHIC UVEITIS

2021 ◽  
Author(s):  
Marie-Helene Errera ◽  
Ana Pratas ◽  
Sylvain Fisson ◽  
Thomas Manicom ◽  
Marouane Boubaya ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Unsupervised Classification ◽  
Control Group ◽  
Serum Samples ◽  
Gm Csf ◽  
Cytokines And Chemokines ◽  
Age Related ◽  
Order Of Magnitude ◽  
Ifn Γ ◽  
Endothelial Growth Factor

To investigate which cytokines, chemokines and growth factors are involved in the immunopathogenesis of idiopathic uveitis, and whether cytokine profiles are associated with. Serum and aqueous humor (AH) samples of 75 patients with idiopathic uveitis were analyzed by multiplex immunoassay. Infectious controls consisted of 16 patients with ocular toxoplasmosis all confirmed by intraocular fluid analyses. Noninfectious controls consisted of 7 patients with Behçet disease related uveitis and 15 patients with sarcoidosis related uveitis. The control group consisted of AH and serum samples from 47 noninflammatory control patients with age-related cataract. In each sample, 27 immune mediators ± IL-21 and IL-23 were measured. In idiopathic uveitis, 13 of the 29 mediators, including most proinflammatory and vascular mediators such as IL-6, IL-8, IL-12, G-CSF, GM-CSF, MCP-1, IP-10, TNF-α and VEGF, were significantly elevated in the aqueous humor when compared to all controls. Moreover, IL-17, IP-10, and IL-21, were significantly elevated in the serum when compared to all controls. We clustered 4 subgroups of idiopathic uveitis using a statistical analysis of hierarchical unsupervised classification, characterized by the order of magnitude of concentrations of intraocular cytokines. The pathogenesis of idiopathic uveitis is characterized by the presence of predominantly proinflammatory cytokines and chemokines and vascular endothelial growth factor with high expression levels as compared to other causes of uveitis. There are indications for obvious Th-1/ IL21-Th17 pathways but also IL9-Th9 and increased IFN-γ-inducing cytokine (IL12) and IFN-γ-inducible CXC chemokine (IP-10). The combined data suggest that immune mediator expression is different among idiopathic uveitis. This study suggests various clusters among the idiopathic uveitis group rather than one specific uveitis entity.

scholarly journals Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

2020 ◽  
Author(s):  
Heping Wang ◽  
Yuqi Li ◽  
Song Han ◽  
Tongtong Niu
Keyword(s):  
Growth Factor ◽  
Aqueous Humor ◽  
Control Group ◽  
Gm Csf ◽  
Macular Holes ◽  
Cytokine Levels ◽  
Idiopathic Macular Holes ◽  
Ifn Γ ◽  
Hepatocyte Growth ◽  
Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes. Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified. Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group , while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group. Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

scholarly journals Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

2021 ◽  
Author(s):  
Heping Wang ◽  
Yuqi Li ◽  
Song Han ◽  
Tongtong Niu
Keyword(s):  
Growth Factor ◽  
Aqueous Humor ◽  
Control Group ◽  
Gm Csf ◽  
Macular Holes ◽  
Cytokine Levels ◽  
Idiopathic Macular Holes ◽  
Ifn Γ ◽  
Hepatocyte Growth ◽  
Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group, while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group.Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

scholarly journals Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole 

2020 ◽  
Author(s):  
Heping Wang ◽  
Yuqi Li ◽  
Song Han ◽  
Tongtong Niu
Keyword(s):  
Macular Hole ◽  
Aqueous Humor ◽  
Significant Positive Correlation ◽  
Control Group ◽  
Idiopathic Macular Hole ◽  
Positive Correlation ◽  
Gm Csf ◽  
Macular Holes ◽  
Idiopathic Macular Holes ◽  
Ifn Γ

Abstract Background Idiopathic macular hole is a common type of ophthalmic disease, and its pathogenesis is unknown. At present, little research about the pathogenesis, especially the immune mechanism, of idiopathic macular hole has been reported. To provide scientific guidance for the treatment and prognosis of idiopathic macular holes, this study examined and analyzed multiple cytokines levels in aqueous humor from patients with idiopathic macular hole. Methods Thirty-eight subjects were divided into cataract control group (n = 17) and idiopathic macular hole group (n = 21). The levels of 48 cytokines in aqueous humor were detected by multiple magnetic beads immunization. Results There were significant differences in cytokine levels in aqueous humor from idiopathic macular holes patients compared with the cataract control group. For example, HGF (p = 0.0001), GM-CSF (p = 0.0111), and IFN-γ (p = 0.0120) were significantly up-regulated, while TNF-α (p = 0.0032), GRO-α (p < 0.0001), and MIF (p < 0.0001) were significantly down-regulated. GM-CSF showed a significant positive correlation with IL-1 (r = 0.67904, p < 0.001), IL-4 (r = 0.76017, p < 0.001), and IFN-γ (r = 0.59922, p = 0.004097). Moreover, NGF and HGF also showed a significant positive correlation (r = 0.64951, p = 0.001441). Conclusion Patients with idiopathic macular hole could exhibit significant variation of the immune reaction in aqueous humor after the disease, including the recruitment of immune cells and the regulation of cytokine expression. This study also implied that it is not rigorous to use macular hole as the control in current studies on aqueous humor cytokines in ophthalmic diseases.

scholarly journals Analysis of multiple cytokines in aqueous humor of patients with idiopathic macular hole

2020 ◽  
Author(s):  
Heping Wang ◽  
Yuqi Li ◽  
Song Han ◽  
Tongtong Niu
Keyword(s):  
Growth Factor ◽  
Aqueous Humor ◽  
Control Group ◽  
Gm Csf ◽  
Macular Holes ◽  
Cytokine Levels ◽  
Idiopathic Macular Holes ◽  
Ifn Γ ◽  
Hepatocyte Growth ◽  
Experimental Group

Abstract Background: Idiopathic macular holes are common ophthalmic manifestations with unknown pathogenesis. Thus far, there has been minimal research regarding the causes of idiopathic macular holes, especially with respect to the underlying immune mechanism. To provide clarity regarding the treatment and prognosis of idiopathic macular holes, specifically regarding the levels of cytokines in affected patients, this study examined and analyzed multiple cytokine levels in aqueous humor from patients with idiopathic macular holes.Methods: This comparative cross-sectional study included 38 patients in two groups: a cataract control group (n=17) and an idiopathic macular hole group (n=21). The levels of 48 cytokines in aqueous humor were detected by multiplex analysis with antibody-coupled magnetic beads. The Kolmogorov–Smirnov test was used to check whether the data were normally distributed; Student’s t-test and the Mann–Whitney U test were used to assess differences in cytokine levels between the two groups. Spearman correlation analysis was used to assess relationships among cytokine levels in the experimental group. Signaling pathways containing cytokines with significantly different expression in the experimental group were identified.Results: There were significant differences in aqueous humor cytokine levels between patients with idiopathic macular holes and patients in the cataract control group. Notably, hepatocyte growth factor (p=0.0001), GM-CSF (p=0.0111), and IFN-γ (p=0.0120) were significantly upregulated in the experimental group, while TNF-α (p=0.0032), GRO-α (p<0.0001), and MIF (p<0.0001) were significantly downregulated in the experimental group. Furthermore, the GM-CSF level showed significant positive correlations with levels of IL-1 (r=0.67904, p<0.001), IL-4 (r=0.76017, p<0.001), and IFN-γ (r=0.59922, p=0.004097) in the experimental group. Moreover, the levels of nerve growth factor and hepatocyte growth factor showed a significant positive correlation (r=0.64951, p=0.001441) in the experimental group.Conclusions: Patients with idiopathic macular holes showed significant variation in aqueous humor immune response after the onset of hole formation, including the recruitment of immune cells and regulation of cytokine expression. Our findings also suggest that it is not appropriate to use patients with macular holes as the control group in studies of aqueous humor cytokine levels in ophthalmic diseases.

scholarly journals Evaluation of aqueous humor and serum clusterin levels in patients with glaucoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fuat Yavrum ◽  
Ufuk Elgin ◽  
Zeynep Adiyaman Kocer ◽  
Vildan Fidanci ◽  
Emine Sen
Keyword(s):  
Anterior Chamber ◽  
Aqueous Humor ◽  
Open Angle Glaucoma ◽  
Control Group ◽  
Posterior Chamber ◽  
Serum Samples ◽  
Chi Square ◽  
New Finding ◽  
High Level ◽  
And Control

Abstract Background To compare the aqueous humor (AH) and the serum clusterin levels of patients with pseudoexfoliation syndrome (PEX), pseudoexfoliation glaucoma (PEXG), and primary open-angle glaucoma (POAG) with each other and with an age- and sex-matched control group. Methods This prospective, cross-sectionalstudy evaluated 92 eyes from 92 adult cases of uncomplicated phacoemulsification and posterior chamber intraocular lens (IOL) implantation. The cases were divided into PEX, PEXG, POAG, and control groups. Serum samples were taken from the antecubital vein just before the surgery, and the AH samples were aspirated at the beginning of the surgery. Kruskal-Wallis H, One-way ANOVA, Mann-Whitney U with Bonferroni correction and Chi-Square tests were used for statistical analysis. Results The serum clusterin levels were the highest in the PEXG group, but no statistically significant differences were observed between the groups (p=0.633). The mean AH clusterin levels were 286.79±29.64 μg/mL in the PEXG group, 263.92±31.70 μg/mL in the PEX group, 272.59±49.71 μg/mL in the POAG group, and 193.50±62.38 μg/mL in the control group (p< 0.001). This came out to be 1.48 times increase for the PEXG group, 1.36 for the PEX group, and 1.41 for the POAG group when compared with the control subjects. Conclusions A higher level of clusterin in the anterior chamber was found to be associated with PEX and PEXG. In addition, a high level of anterior chamber clusterin in POAG, which is a new finding, showed that this molecule might be important not only in pseudoexfoliation, but also other types of glaucoma like POAG.

scholarly journals Aqueous humor cytokine levels through microarray analysis and a sub-analysis based on optical coherence tomography in wet age-related macular degeneration patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jin-Ho Joo ◽  
Hyejee Kim ◽  
Jae-Ho Shin ◽  
Sang Woong Moon
Keyword(s):  
Optical Coherence Tomography ◽  
Growth Factor ◽  
Inflammatory Cytokines ◽  
Age Related Macular Degeneration ◽  
Gm Csf ◽  
Age Related ◽  
Ifn Γ ◽  
Low Levels ◽  
Wet Amd

Abstract Background To identify disease-specific cytokine and growth factor profile differences in the aqueous humor between wet age-related macular degeneration (AMD) patients and age-matched controls and to correlate their levels with the optical coherence tomography (OCT) findings. Methods Aqueous humors were obtained from 13 wet AMD eyes and 10 control eyes. Twenty cytokines and growth factors were measured using a RayBio antibody microarray technology in wet AMD and control eyes. Results The samples obtained from wet AMD patients exhibited a significantly increased expression of MCP-1, MIP-1α, MIP-1β, and vascular endothelial growth factor (VEGF). Subretinal fluid (SRF) patients showed significantly lower levels of proinflammatory cytokines, such as IL-1α and GM-CSF, than those without SRF. Pigment epithelial detachments (PED) patients showed lower levels of inflammatory cytokines, such as GM-CSF, IFN-γ, and TNF-α, than those without PED. Subretinal tissue (SRT) patients showed a higher level of IFN-γ than those without SRT. Compared with the controls, type 1 macular neovascularization (MNV) patients showed increased levels of MCP-1, MIP-1α, and MIP-1β, but not VEGF (p = 0.083). However, type 2 MNV patients showed increased levels of MCP-1 and VEGF (p = 0.040 and p = 0.040). Conclusion Inflammatory cytokines varied according to the type of AMD- and OCT-based parameters. Our observation of low levels of VEGF in patients with type 1 MNV implies that the inhibition of VEGF alone appears to be insufficient treatment for these patients and that cytokines such as MCP-1, MIP-1α, and MIP-1β should be modulated. And the presence of SRF in MNV may be associated with a positive prognosis because we found relatively low levels of proinflammatory cytokines.

Serum cytokine profile during subcutaneous implantation of the decellularized esophagus matrix in rats

2020 ◽  
Vol 35 (3) ◽  
pp. 446-455
Author(s):  
Karina Melkonyan ◽  
Ramazan Nakokhov ◽  
Tatyana Rusinova ◽  
Yana Yutskevich ◽  
Ilya Bykov ◽  
...  
Keyword(s):  
Dynamic Change ◽  
Healing Process ◽  
Cytokine Profile ◽  
Control Group ◽  
Wound Healing Process ◽  
Subcutaneous Implantation ◽  
Serum Cytokine ◽  
Serum Samples ◽  
Rat Serum ◽  
Gm Csf

Aim to study non-specific immune response characteristics (serum cytokine profile) in rats after subcutaneous implantation of the decellularized esophagus matrix. Methods Data were obtained in Wistar rats. The rats underwent subcutaneous implantation of decellularized esophagus (DE) and native allogeneic esophagus (NE). Explantation of sampling were carried out on the 7th, 14th and 21st day of the experiment. Explanted NEs and DEs were processed for histologic examination. The content of IL1α, IL2, IL4, IL17А, TNFα, IFNγ and GM-CSF in serum samples were tested by ELISA. Results In rat serum with DEs on the 7th day of the experiment it was significant increase in IL1α level in comparison with control group, IL2, TNFα, IL4 levels did not differ from the control group levels that indicates the stabilization of inflammation. The content of IL17A, IFNγ and GM-CSF significantly decreased compared to control. On the 14th day, IL17A concentration analysis showed a sharp decrease in comparison with the the 7th experimental day. We found decrease in IL1α level vs control group and decrease in IFNγ level vs 7th day. On the 21st experimental day was shown a significant decrease in the IL17A, IFNγ and IL1α content in DE rats. Conclusions It was found dynamic change in studied rat cytokine concentrations that correspond to favourable clinical picture in DE group in comparison with an active inflammatory reaction in NE group. IL1α, IL4, IL17A and IFNγ concentrations reflect positive dynamics of the wound healing process and the absence of local inflammation and rejection of decellularized matrices.

scholarly journals Is Saffron Able to Prevent the Dysregulation of Retinal Cytokines Induced by Ocular Hypertension in Mice?

2021 ◽  
Vol 10 (21) ◽  
pp. 4801
Author(s):  
José A. Fernández-Albarral ◽  
Miguel A. Martínez-López ◽  
Eva M. Marco ◽  
Rosa de Hoz ◽  
Beatriz Martín-Sánchez ◽  
...  
Keyword(s):  
Ocular Hypertension ◽  
Proinflammatory Cytokines ◽  
Control Group ◽  
Chemokine Production ◽  
Cytokines And Chemokines ◽  
Saffron Extract ◽  
Anti Inflammatory ◽  
Contralateral Eye ◽  
Laser Induction ◽  
Endothelial Growth Factor

Cytokine- and chemokine-mediated signalling is involved in the neuroinflammatory process that leads to retinal ganglion cell (RGC) damage in glaucoma. Substances with anti-inflammatory properties could decrease these cytokines and chemokines and thus prevent RGC death. The authors of this study analysed the anti-inflammatory effect of a hydrophilic saffron extract standardized to 3% crocin content, focusing on the regulation of cytokine and chemokine production, in a mouse model of unilateral laser-induced ocular hypertension (OHT). We demonstrated that following saffron treatment, most of the concentration of proinflammatory cytokines (IL-1β, IFN-γ, TNF-α, and IL-17), anti-inflammatory cytokines (IL-4 and IL-10), Brain-derived Neurotrophic Factor (BDNF), Vascular Endothelial Growth Factor (VEGF), and fractalkine were unaffected in response to laser-induced OHT in both the OHT eye and its contralateral eye. Only IL-6 levels were significantly increased in the OHT eye one day after laser induction compared with the control group. These results differed from those observed in animals subjected to unilateral OHT and not treated with saffron, where changes in cytokine levels occurred in both eyes. Therefore, saffron extract regulates the production of proinflammatory cytokines, VEGF, and fractalkine induced by increasing intraocular pressure (IOP), protecting the retina from inflammation. These results indicate that saffron could be beneficial in glaucoma by helping to reduce the inflammatory process.

Booster inoculations of the AE37 peptide vaccine enhance immunological responses in a phase II study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3095-3095
Author(s):  
Eleftheria A Anastasopoulou ◽  
Efi Pappou ◽  
Panagiotis Tzonis ◽  
Alexandros Ardavanis ◽  
Sathibalan Ponniah ◽  
...  
Keyword(s):  
High Risk ◽  
Immune Responses ◽  
Phase Ii ◽  
Clinical Efficacy ◽  
Peptide Vaccine ◽  
Significant Risk ◽  
Control Group ◽  
Gm Csf ◽  
Ifn Γ ◽  
Disease Free

3095 Background: We are conducting a multicenter randomized phase II trial of AE37, the Ii-Key hybrid peptide of HER2 776-790 (AE36). The purpose of the study is to determine if the AE37 vaccine can prevent recurrence in disease-free conventionally treated node-positive (NP) and high-risk node-negative (NN) breast cancer patients at significant risk for recurrence. Since clinical efficacy is anticipated to occur as the result of long lasting memory immune responses induced by vaccination, repeated booster inoculations were scheduled as part of the trial. Here we present data on immune responses in patients who received boosters up to 24 months after completion of the primary vaccination series (PVS). Methods: The trial is enrolling NP or high-risk NN patients with any degree of HER2 expression (IHC 1-3+ or FISH > 1.2) rendered disease-free following standard of care therapy. The vaccine group (VG) received AE37+GM-CSF and control group (CG) GM-CSF alone in 6 monthly i.d. inoculations followed by boosters administered every 6 months x 4. Immunologic responses were assessed in vivo by dermal reactions at the inoculation site, and in vitro, against the AE36 peptide, with proliferation and IFN-γ ELISPOT assays. Results: 25 patients in the VG and 23 in the CG have completed their boosters. After the last booster (BRC24), 100%, 54% and 54% in the VG (vs. 9%, 18% and 27% in the CG) responded by dermal reaction, proliferation and IFN-γ ELISPOT, respectively. Mean dermal reactions (orthogonal mean in mm) in vaccinated patients was 25.9±3.13 at completion of the PVS (R6) and increased to 35.47±4.35 at BRC24 (p=0.01). VG patients increased their proliferation response (stimulation index, SI) to AE36 from 0.97±0.046 at baseline (R0) before vaccination to 2.27±0.57 at R6 (p=0.0003) which was maintained until BRC24 (SI 2.21±0,33, p<0.0001). The number of IFN-γ specific spots/106 PBMC increased from 26.88±12.36 at R0 to 40.35±17.02 (p=0.07) at R6, up to 62±16.82 (p=0.0076) at BRC24. Conclusions: Our data demonstrate that AE37 vaccine boosters enhance the immune responses against HER elicited during the PVS, thus sustaining long lasting immunity, a prerequisite for possible clinical efficacy which is currently being evaluated. Clinical trial information: NCT00524277.

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