inflammatory diseases
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Cytokine ◽  
2022 ◽  
Vol 150 ◽  
pp. 155781
Author(s):  
Mathilde Harel ◽  
Sébastien Fauteux-Daniel ◽  
Charlotte Girard-Guyonvarc'h ◽  
Cem Gabay

Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Olalekan Lee Aiyegbusi ◽  
Lavinia Ferrante di Ruffano ◽  
Ameeta Retzer ◽  
Philip N. Newsome ◽  
Christopher D. Buckley ◽  
...  

Abstract Background Tissue-agnostic drug development provides a paradigm shift in precision medicine and requires innovative trial designs. However, outcome selection for such trials can prove challenging. The objectives of this review were to: Identify and map core outcome sets (COS), across 11 immune-mediated inflammatory diseases (IMIDs) in order to facilitate the selection of relevant outcomes across the conditions for innovative trials of tissue-agnostic drug therapies. Compare outcomes or endpoints recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to identify and highlight similarities and differences. Methods The Core Outcome Measures in Effectiveness Trials (COMET), International Consortium for Health Outcomes Measurement (ICHOM), FDA and EMA databases were searched from inception to 28th December 2019. Two reviewers independently screened titles and abstracts of retrieved entries and conducted the subsequent full text screening. Hand searching of the reference lists and citation searching of the selected publications was conducted. The methodological quality of the included peer-reviewed articles was independently assessed by the reviewers based on the items of the COS–Standards for Development recommendations (COS–STAD) checklist. Core outcomes from the included publications were extracted and mapped across studies and conditions. Regulatory guidance from FDA and EMA, where available for clinical trials for the IMIDs, were obtained from their databases and recommendations on outcomes to measure directly compared. Results Forty-four COS publications were included in the final analysis. Outcomes such as disease activity, pain, fatigue, quality of life, physical function, work limitation/productivity, steroid use and biomarkers were recommended across majority of the conditions. There were significant similarities and differences in FDA and EMA recommendations. The only instance where either regulatory body directly referenced a COS was for jSLE—both referenced the Paediatric Rheumatology International Trials Organization (PRINTO) COS. Conclusions The findings from this systematic review provide valuable information to inform outcome selection in tissue-agnostic trials for IMIDs. There is a need for increased collaboration between regulators and COS developers and inclusion of regulators as key stakeholders in COS development to enhance the quality of COS. Trial registration Not registered.


Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 164
Author(s):  
Hannah K. Fitzgerald ◽  
Sinead A. O’Rourke ◽  
Eva Desmond ◽  
Nuno G. B. Neto ◽  
Michael G. Monaghan ◽  
...  

The extracellular parasite and causative agent of African sleeping sickness Trypanosoma brucei (T. brucei) has evolved a number of strategies to avoid immune detection in the host. One recently described mechanism involves the conversion of host-derived amino acids to aromatic ketoacids, which are detected at relatively high concentrations in the bloodstream of infected individuals. These ketoacids have been shown to directly suppress inflammatory responses in murine immune cells, as well as acting as potent inducers of the stress response enzyme, heme oxygenase 1 (HO-1), which has proven anti-inflammatory properties. The aim of this study was to investigate the immunomodulatory properties of the T. brucei-derived ketoacids in primary human immune cells and further examine their potential as a therapy for inflammatory diseases. We report that the T. brucei-derived ketoacids, indole pyruvate (IP) and hydroxyphenylpyruvate (HPP), induce HO-1 expression through Nrf2 activation in human dendritic cells (DC). They also limit DC maturation and suppress the production of pro-inflammatory cytokines, which, in turn, leads to a reduced capacity to differentiate adaptive CD4+ T cells. Furthermore, the ketoacids are capable of modulating DC cellular metabolism and suppressing the inflammatory profile of cells isolated from patients with inflammatory bowel disease. This study therefore not only provides further evidence of the immune-evasion mechanisms employed by T. brucei, but also supports further exploration of this new class of HO-1 inducers as potential therapeutics for the treatment of inflammatory conditions.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Kang Chen ◽  
Yong Yao ◽  
Xinxin Mao ◽  
Hui You ◽  
Linjie Wang ◽  
...  

Abstract Background The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. Case presentation A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. Conclusion Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.


2022 ◽  
pp. jrheum.211148
Author(s):  
Jessica Widdifield ◽  
Lihi Eder ◽  
Simon Chen ◽  
Jeffrey C. Kwong ◽  
Carol Hitchon ◽  
...  

Objective We assessed COVID-19 vaccine uptake among individuals with immune-mediated inflammatory diseases (IMID) and the Ontario general population. Methods We studied all residents 16 years and older who were alive and enrolled in Ontario's universal health insurance plan as of December 14, 2020 when vaccination commenced (n=12,435,914). Individuals with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), psoriasis (PsO), and inflammatory bowel disease (IBD) were identified using established disease-specific case definitions applied to health administrative data. Vaccination status was extracted from the provincial COVaxON registry. Weekly cumulative proportions of first and second doses up until October 3, 2021 were expressed as the vaccinated percentage of each disease group, and compared to the general Ontario population, and stratified by age. Results By October 3, 2021, the cumulative percentage with at least one dose was 82.1% for the general population, 88.9% for RA, 87.4% for AS, 90.6% for PsA, 87.3% for PsO, and 87.0% for IBD. There was also a higher total cumulative percentage with two doses among IMIDs (83.8-88.2%) vs the general population (78.0%). The difference was also evident when stratifying by age. Individuals with IMIDs in the youngest age group initially had earlier uptake than the general population but remain the lowest age group with two doses (70.6% in the general population vs. 73.7-79.2% across IMID groups). Conclusion While implementation of COVID-19 vaccination programs has differed globally, these Canadian estimates are the first to reassuringly show higher COVID-19 vaccine uptake among individuals with IMIDs.


2022 ◽  
Vol 18 (1) ◽  
Author(s):  
Leila Khani ◽  
Mir Hadi Jazayeri ◽  
Reza Nedaeinia ◽  
Mahmood Bozorgmehr ◽  
Seyed Masood Nabavi ◽  
...  

Abstract Background Multiple sclerosis (MS) and neuromyelitis optica syndrome disease (NMOSD) are inflammatory diseases of the central nervous system. The pathogenesis and treatments for these two conditions are very different. Natural killer (NK) and natural killer T (NKT) cells are immune cells with an important role in shaping the immune response. B cells are involved in antigen presentation as well as antibody and cytokine production. There is conflicting evidence of the roles of NK, NKT, and B cells in the two conditions. We aimed to compare the frequency of CD3−CD16+CD56+NK, CD3+ CD56+ NKT, and CD5+CD19+ B cells in the peripheral blood and serum Interleukin-10 (IL-10) in patients with MS and NMOSD. Methods CD19+CD5+ B, CD3− CD16+CD56+ NK, and CD3+CD56+ NKT cells were quantitated by flow cytometry in 15 individuals with Interferon-Beta (IFN-β) treated relapsing–remitting MS (RRMS), 15 untreated RRMS, and 15 NMOSD patients as well as 30 healthy controls (HC). Serum IL-10 was measured using an enzyme-linked immunosorbent assay (ELISA). Results The percentage of CD3−CD56+CD16+ NK cells in the peripheral blood of IFN-treated MS (1.81 ± 0.87) was significantly lower than for untreated RRMS (4.74 ± 1.80), NMOSD (4.64 ± 1.26) and HC (5.83 ± 2.19) (p < 0.0001). There were also differences for the percentage of CD3−CD16+ and CD3−CD56+ cells (p < 0.001 and p < 0.0007; respectively). IFN-treated RRMS (2.89 ± 1.51) had the lowest proportion of CD3+CD56+ among the study groups (p < 0.002). Untreated RRMS (5.56 ± 3.04) and NMOSD (5.47 ± 1.24) had higher levels of CD3+CD56+ than the HC (3.16 ± 1.98). The mean percentage of CD19+CD5+ B cells in the peripheral blood of untreated RRMS patients (1.32 ± 0.67) was higher compared to the patients with NMOSD (0.30 ± 0.20), HC (0.5 ± 0.22) and IFN-treated RRMS (0.81 ± 0.17) (p < 0.0001). Serum interleukin-10 was significantly higher in the IFN-treated RRMS (8.06 ± 5.39) and in HC (8.38 ± 2.84) compared to untreated RRMS (5.07 ± 1.44) and the patients with NMOSD (5.33 ± 2.56) (p < 0.003). Conclusions The lower proportion of CD3−CD56+ CD16+ NK and CD3+CD56+ cells in peripheral blood of IFN-treated RRMS compared to other groups suggests the importance of immunomodulation in patients with RRMS disorder. Based on the differences in CD19+CD5+ B cells and serum IL-10 between patients and HC, supplementary assessments could be of value in clarifying their roles in autoimmunity.


Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 352
Author(s):  
Carolina F. F. A. Costa ◽  
Benedita Sampaio-Maia ◽  
Ricardo Araujo ◽  
Diana S. Nascimento ◽  
Joana Ferreira-Gomes ◽  
...  

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.


2022 ◽  
Author(s):  
Jun Xiao ◽  
Shuo-Qi Zhang ◽  
Xin Chen ◽  
Yue Tang ◽  
Man Chen ◽  
...  

Abstract Objective: Several autoimmune CNS inflammatory diseases, including autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorders (AQP4-IgG+ NMOSD) often presented initially with similar infectious meningitis-like symptoms. However, it was not easy to differentiate them at disease onset without antibody detection. The present study aimed to compare the clinical, immunological and radiological features among the three diseases. Methods: In our single-center cohorts, 9 A-GFAP-A, 17 MOGAD and 11 AQP4-IgG+ NMOSD patients mimicking infectious meningitis as initial symptoms were retrospectively included. The autoantibodies were detected with cell-based assays. The clinical, immunological and radiological characteristics of the three groups were summarized. Results: AQP4-IgG+ NMOSD patients were statistically more often in men (10, 90.9%, P=0.003). Tremor was predominated in A-GFAP-A (4, 44.4%) over MOGAD (1, 5.9%, P= 0.034) and never found in AQP4-IgG+NMOSD (0, P=0.026). The Modified Rankin Score (mRS) at the clinical nadir of diseases was lower in AQP4-IgG+NMOSD (2.2 [IQR, 1-3]) compared to A-GFAP-A (3.7 [IQR, 3-5], P=0.04). On CSF examination, white blood cell count (WBC) was higher in A-GFAP-A (median, 272×106/L [range, 0-1600]) compared to AQP4-IgG+NMOSD (median, 12×106/L [range, 0-48], P=0.049). Significant increase in CSF protein (1490.7±871.2 mg/L), lactic acid (3.43±0.81 mmol/L), IgG (130.9±60.4 mg/L), IgM (8.6±6.1mg/L) and IgA (23.0±11.4mg/L) levels in A-GFAP-A was found compared to MOGAD (CSF protein: 606.7±379.4 mg/L, P<0.001; lactic acid: 2.15 ± 0.62mmol/L, P<0.001; IgG: 77.9±71.3 mg/L, P=0.043; IgM, 2.7±2.9mg/L, P=0.002; IgA, 11.3±12.1mg/L, P=0.012) and AQP4-IgG+NMOSD (CSF protein: 441.8±178.0 mg/L, P<0.001; lactic acid: 2.40 ± 0.66 mmol/L, P=0.003; IgG, 53.2±30.3 mg/L, P=0.01; IgM, 2.1±3.9mg/L, P=0.003; IgA, 5.2±5.0mg/L, P=0.001). Over half of the A-GFAP-A patients (5/8, 62.5%) showed small (<2 cm), symmetrical lesions in ganglia and thalamus (5/8, 62.5%), but never in MOGAD (0%, P=0.001) and AQP4-IgG+NMOSD (0%, P=0.026). Diffuse meningeal enhancement was common in A-GFAP-A (8, 88.9%) compared to MOGAD (5, 29.4%, P=0.011) and AQP4-IgG+NMOSD (1/6, 16.7%, P=0.011). Acute disseminated encephalomyelitis (ADEM) -like lesions occurred frequently in MOGAD (6/16, 37.5%) but never in A-GFAP-A and AQP4-IgG+NMOSD (P=0.02). Conclusion: Our study demonstrated that several signs including the symptom of tremor, a more severe disease course, higher CSF immunological profiles and ganglia bilateral symmetrical lesions, diffuse meningeal enhancement were distinct features in A-GFAP-A, and ADEM-like lesions occurred only in MOGAD mimicking infectious meningitis as initial symptoms, providing possible clinical implications for patient differential diagnosis.


Immuno ◽  
2022 ◽  
Vol 2 (1) ◽  
pp. 104-117
Author(s):  
Dennis Awuah ◽  
Alisa Ruisinger ◽  
Meshal Alobaid ◽  
Chidimma Mbadugha ◽  
Amir M. Ghaemmaghami

The peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor expressed in dendritic cells (DCs), where it exerts anti-inflammatory responses against TLR4-induced inflammation. Recently, microRNA-511 (miR-511) has also emerged as a key player in controlling TLR4-mediated signalling and in regulating the function of DCs. Interestingly, PPARγ has been previously highlighted as a putative target of miR-511 activity; however, the link between miR-511 and PPARγ and its influence on human DC function within the context of LPS-induced inflammatory responses is unknown. Using a selection of miR-511-3p-specific inhibitors and mimics, we demonstrate for the first time that knockdown or overexpression of miR-511-3p inversely correlates with PPARγ mRNA levels and affects its transcriptional activity following treatment with rosiglitazone (RSG; PPARγ agonist), in the presence or absence of LPS. Additionally, we show that PPARγ-mediated suppression of DC activation and pro-inflammatory cytokine production in miR-511-3p knockdown DCs is abrogated following overexpression of miR-511-3p. Lastly, PPARγ activation suppressed LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. Our data thus suggests that PPARγ-induced modulation of DC phenotype and function is influenced by miR-511-3p expression, which may serve as a potential therapeutic target against inflammatory diseases.


2022 ◽  
Author(s):  
Pengcheng Yan ◽  
Xiaoning Song ◽  
Joanne Tran ◽  
Runfa Zhou ◽  
Xinran Cao ◽  
...  

Abstract Viral myocarditis (VMC), which is most prevalently caused by Coxsackievirus B3 (CVB3) infection, is a serious clinical condition characterized by cardiac inflammation. Dapagliflozin, a kind of sodium glucose co-transporters 2(SGLT-2) inhibitor, exhibited protective effects on plenty of inflammatory diseases, while its effect on viral myocarditis has not been studied. Recently we found the protective effect of dapagliflozin on VMC. After CVB3 infection, dapagliflozin were given orally to Balb/c male mice for 8 days and then the severity of myocarditis was assessed. Our results indicated that dapagliflozin significantly alleviated the severity of viral myocarditis, elevated the survival rate, and ameliorated cardiac function. Besides, dapagliflozin can decrease the level of proinflammatory cytokines included IL-1β, IL-6, TNF-α. Furthermore, dapagliflozin can inhibit macrophages differentiate to classically activated macrophages (M1) in cardiac tissue and activate the Stat3 signal pathway which is reported to promote polarization of the alternatively activated macrophage (M2). In conclusion, our study demonstrates that dapagliflozin alleviates myocardial inflammation by regulating the macrophage polarization and Stat3-related pathways in coxsackie virus B3-induced acute viral myocarditis.


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