Alarmins in autoimmune diseases

Danieli, Maria Giovanna; Antonelli, Eleonora; Piga, M.; Claudi, Ilaria; Palmeri, Davide; Tonacci, Alessandro; Allegra, Alessandro; Gangemi, Sebastiano

doi:10.1016/j.autrev.2022.103142

Cited by 26 publications

(20 citation statements)

References 230 publications

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“…Because HMGB1 can only be secreted following acetylation and acetylated HMGB1 can act as a damage-associated molecular pattern (DAMP) molecule to induce sterile inflammation and immune responses through different mechanisms ( 5 , 8 ), we mainly focused on acetylated HMGB1 during early pregnancy. From days 1 to 3, there was no detectable acetylated HMGB1 immunofluorescence in mouse uteri ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

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The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization

Chen

et al. 2023

Front. Immunol.

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IntroductionHigh-mobility group box 1 (HMGB1) is a non-histone nuclear protein and can be extracellularly secreted to induce sterile inflammation. Although uterine deletion of HMGB1 causes implantation and decidualization defects, how secreted HMGB1 is involved in mouse early pregnancy is still unknown.MethodsMouse models, mouse primary endometrial cells and human endometrial cell lines were used in this study. Both immunofluorescence and Western blot were performed to show the localization and relative level of HMGB1 and acetylated HMGB1, respectively. Relative mRNA levels were analyzed by real time RT-PCR.ResultsThe secreted HMGB1 was detected in uterine lumen fluid in mouse periimplantation uterus. There is an obvious difference for secreted HMGB1 levels in uterine fluid between day 4 of pregnancy and day 4 of pseudopregnancy, suggesting the involvement of blastocysts during HMGB1 secretion. Trypsin is clearly detected in mouse blastocyst cavity and in the supernatant of cultured blastocysts. Trypsin significantly stimulates HB-EGF production through activating PAR2 and ADAM17. Uterine injection of PAR2 inhibitor into day 4 pregnant mice significantly reduces the number of implantation sites. HB-EGF released from luminal epithelium can induce mouse in vitro decidualization. The conditioned medium collected from trypsin-treated luminal epithelium is able to induce in vitro decidualization, which is suppressed by EGFR inhibitor. Intrauterine injection of glycyrrhizin (HMGB1 inhibitor) can significantly inhibit mouse embryo implantation. We also showed that exogenous HMGB1 released from human epithelial cells are able to induce human in vitro decidualization.ConclusionTrypsin can induce decidualization of stromal cells via PAR2-HMGB1-ADAM17-HB-EGF from luminal epithelium.

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Section: Resultsmentioning

confidence: 99%

“…HMGB1 release can be caused by stress and damaged cells ( 7 ). The secreted extracellular HMGB1 can act as a damage-associated molecular pattern (DAMP) molecule to induce sterile inflammation and immune responses through different mechanisms ( 5 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization

Chen

et al. 2023

Front. Immunol.

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“…HBD is one of the alarmins that are endogenous peptides or proteins, which are released after cell damage in the extracellular milieu. They have a strong proinflammatory action, stimulating innate immunity and triggering antigen-presenting cells that in turn activate the adaptive immune response [25].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of serum Level of Human Beta Defensin 1 patients With Alopecia Areata

El-moneam

Ebrahim²,

Mustafa³

et al. 2022

Benha Journal of Applied Sciences

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Alopecia areata is an autoimmune disease characterized by non-scarring hair loss in single or multiple areas of the scalp, face or body. Human beta-defensin 1 is a protein that in humans is encoded by the DEFB1 gene. Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Human beta defensin 1 was purified from hemodialysate fluid, but its tissue sources were not identified. Aim:To evaluate serum level of human beta defensin 1 to reveal its role in alopecia areata pathogenesis and to relate with studied clinical parameters. Patients and methods: This prospective casecontrol study was included fourty patients with AA (Group A) and fourty age and sex matched apparently healthy subjects as a control group (Group B). Patients were selected from the Dermatology outpatient clinic of Benha University Hospitals in the period between December 2018 and June 2019. Results:we found that AA group showed no significant difference in serum level of HBD-1 when compared to control group (p=0.03). HBD-1 concentration was not considered as predictor of AA.Conclusion: HBD-1 concentration was not considered as a predictor of AA susceptibility and severity.

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“…Its accurate prediction is essential in informing clinical decision-making. The discovery of a convenient model useful for prediction could be driven to the removal of less-necessary clinical examinations, saving time and money, and reducing the burden on the patients (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease

Gui

et al. 2022

Front. Immunol.

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BackgroundAnti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease (anti-MDA5 DM-ILD) is a disease with high mortality. We sought to develop an effective and convenient prediction tool to estimate mortality risk in patients with anti-MDA5 DM-ILD and inform clinical decision-making early.MethodsThis prognostic study included Asian patients with anti-MDA5 DM-ILD hospitalized at the Nanjing Drum Hospital from December 2016 to December 2020. Candidate laboratory indicators were retrospectively collected. Patients hospitalized from 2016 to 2018 were used as the discovery cohort and applied to identify the optimal predictive features using a least absolute shrinkage and selection operator (LASSO) logistic regression model. A risk score was determined based on these features and used to construct the mortality risk prediction model in combination with clinical characteristics. Results were verified in a temporal validation comprising patients treated between 2019 and 2020. The primary outcome was mortality risk within one year. The secondary outcome was overall survival. The prediction model’s performance was assessed in terms of discrimination, calibration, and clinical usefulness.ResultsThis study included 127 patients, (72 men [56.7%]; median age, 54 years [interquartile range, 48-63 years], split into discovery (n = 87, 70%) and temporal validation (n=37, 30%) cohorts. Five optimal features were selected by LASSO logistic regression in the discovery cohort (n = 87) and used to construct a risk score, including lymphocyte counts, CD3+CD4+ T-cell counts, cytokeratin 19 fragment (CYFRA21-1), oxygenation index, and anti-Ro52 antibody. The retained predictive variables in the final prediction model were age, Heliotrope, fever, and risk score, and the most predictive factor was the risk score. The prediction model showed good discrimination (AUC: 0.915, 95% CI: 0.846–0.957), good calibration (Hosmer–Lemeshow test, P = 0.506; Brier score, 0.12), and fair clinical usefulness in the discovery cohort. The results were verified among patients in the temporal validation cohort (n = 38). We successfully divided patients into three risk groups with very different mortality rates according to the predictive score in both the discovery and validation cohorts (Cochran-Armitage test for trend, P < 0.001).ConclusionsWe developed and validated a mortality risk prediction tool with good discrimination and calibration for Asian patients with anti-MDA5 DM-ILD. This tool can offer individualized mortality risk estimation and inform clinical decision-making.

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Alarmins in autoimmune diseases

Cited by 26 publications

References 230 publications

The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization

The regulation and function of acetylated high-mobility group box 1 during implantation and decidualization

Evaluation of serum Level of Human Beta Defensin 1 patients With Alopecia Areata

Prediction model for the pretreatment evaluation of mortality risk in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with interstitial lung disease

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