HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study

Cazzato, Gerardo; Colagrande, Anna; Cimmino, Antonietta; Cicco, Gerolamo; Scarcella, Vincenza Sara; Tarantino, Piero; Lospalluti, Lucia; Romita, Paolo; Foti, Caterina; Demarco, Aurora; Sablone, Sara; Candance, Pragnell Maria Victoria; Cicco, Sebastiano; Lettini, Teresa; Ingravallo, Giuseppe; Resta, Leonardo

doi:10.3390/biom11081219

Cited by 12 publications

(10 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cazzato et al have observed in their study that there is no difference between CD4 and CD8 levels in skin biopsy samples in healthy volunteers and COVID-19 positive patients. However, in their study, they have also concluded that HMGB1 levels rise significantly in COVID-19 positive patients [12].…”

Section: Discussionmentioning

confidence: 87%

Is there a relationship between HMGB1 levels and clinical conditions of patients tested positive for COVID-19?

Gundogdu¹,

Tanriverdi²,

Celikturk³

et al. 2022

Med-Science

View full text Add to dashboard Cite

Severe COVID-19 may be complicated by acute respiratory distress syndrome, sepsis and septic shock, which can lead to death. These life-threatening conditions are supposed to be the outcome of immune system overactivity, which causes cytokine storm syndrome and multiple organ failure. High mobility group box-1 (HMGB1) is one of the damages associated with molecular model molecules (DAMPs), which plays a role in the pathogenesis of various inflammatory diseases and infections where many studies have been conducted. In this study, the role of HMGB1 in COVID-19 positive cases, which could be considered a potential diagnosis and treatment method, is investigated. COVID-19 patients, who were hospitalized to our clinic in Sanko University Hospital, were included in this study. Blood samples were taken from patients to measure their HMGB1 level which was then compared with their clinical severity. It is observed that HMGB1 levels rise in COVID-19 patients when compared to the control group, but the severity of the illness does not get particularly affected by their HMGB1 levels.

show abstract

Section: Discussionmentioning

confidence: 87%

Is there a relationship between HMGB1 levels and clinical conditions of patients tested positive for COVID-19?

Gundogdu¹,

Tanriverdi²,

Celikturk³

et al. 2022

Med-Science

View full text Add to dashboard Cite

show abstract

“…Therefore, although HO-1 was detected in specific tissue samples we could not assess the degree of protein expression. Another study has also described the detection of HO-1 in skin tissue samples from COVID-19 patients [ 20 ]. However, the study included patients with mild symptoms and the specimens were obtained from specific skin lesions and reported downregulation of HO-1 protein expression when compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

Increase of HO-1 Expression in Critically Ill COVID-19 Patients Is Associated with Poor Prognosis and Outcome

et al. 2022

View full text Add to dashboard Cite

Heme-oxygenase (HO)-1 is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties and previous reports have also emphasized the antiviral properties of HO-1, either directly or via induction of interferons. To investigate the potential role of HO-1 in patients with coronavirus disease 2019 (COVID-19), the present study assessed changes in HO-1 expression in whole blood and tissue samples. Upregulation of HO-1 protein was observed in lung, liver, and skin tissue independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence. A significant increase of blood HO-1 mRNA levels was observed in critically ill COVID-19 patients compared to those in severe COVID-19 patients and healthy controls. This increase was accompanied by significantly elevated levels of serum ferritin and bilirubin in critically ill compared to patients with severe disease. Further grouping of patients in survivors and non-survivors revealed a significant increase of blood HO-1 mRNA levels in the later. Receiver operating characteristic (ROC) analysis for prediction of ICU admission and mortality yielded an AUC of 0.705 (p = 0.016) and 0.789 (p = 0.007) respectively indicating that HO-1 increase is associated with poor COVID-19 progression and outcome. The increase in HO-1 expression observed in critically ill COVID-19 patients could serve as a mechanism to counteract increased heme levels driving coagulation and thrombosis or as an induced protective mechanism.

show abstract

“…The expression of HMGB1 [18], TIM-3 [19] and HO-1 [20,21] was assessed by highlighting the chromogen signal on the cytoplasm, in the nucleus or extracellular medium of the samples analyzed. For HMGB1, TIM-3 and HO-1, a score was assigned, summing the different degrees of staining intensity (grade 0 = no staining; grade 1 = weak staining; grade 2 = moderate staining; grade 3 = intense staining) plus the score for the percentage extension of the mass (score 0: <1%; score 1: 1-25%; score 2: 26-50%; score 3: 51-74%; score 4: ≥75%).…”

Section: Methodsmentioning

confidence: 99%

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study

Filoni

Cicco

Cazzato

et al. 2022

Life

Self Cite

View full text Add to dashboard Cite

Background: Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications of recessive dystrophic epidermolysis bullosa (RDEB). We recently demonstrated a reduction in immune cell peritumoral infiltration in RDEB patients with cSCC, together with a reduction in CD3+, CD4+, CD68+ and CD20 lymphocytes as compared to primary and secondary cSCC in patients without RDEB. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity. Objective: Patients with RDEB are known to be at increased risk of developing skin cancers, including the dreaded squamous cell carcinoma of the. Tendentially, cSCCs that arise in the context of EBDR are more aggressive and lead to statistically significant bad outcomes compared to cSCCs developed on the skin of patients without EBDR. In an attempt to study the microenvironment of these lesions, we conducted an immunohistochemical analysis study of proteins that could be actively involved in the genesis of this type of malignant neoplasms. Methods: In this retrospective study, the OH1-HMGB1-TIM3 activation axis, as correlated to the T lymphocytes cell count, was assessed in biopsy samples from 31 consecutive cases consisting of 12 RDEB patients with cSCC, 12 patients with primary cSCC and 7 RDEB patients with pseudoepitheliomatous cutaneous hyperplasia. Parametric Student’s t-test was applied for normally distributed values, such as CD4+ and CD8+, and non-parametric Mann–Whitney test for non-normally distributed values, such as HMGB-1, TIM-3 and HO-1. Results: In RDEB patients with cSCC and with pseudoepitheliomatous hyperplasia, the expression of CD4 T helper lymphocytes was lower than in the peritumoral infiltrate found in primary cSCC. CD8 cytotoxic T lymphocytes were increased in primary cSCC compared to the other two groups. An increased HMGB1 expression was evident in both primary and RDEB cSCC. TIM3 expression was higher in RDEB patients with cSCC compared to the other two groups. A significantly reduced immunohistochemical expression of HO-1 was evident in the tumoral microenvironment of cSCC-RDEB as compared to primary cSCC. Conclusions: These data suggest that a reduced immune cell peritumoral infiltration in RDEB patients could be responsible, in the complexity of the mechanisms of carcinogenesis and host response, of the particular aggressiveness of the cSCC of RDEB patients, creating a substrate for greater local immunosuppression, which, potentially, can “open the doors” to development and eventual metastasis by this malignant neoplasm.

show abstract

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study

Cited by 12 publications

References 37 publications

Is there a relationship between HMGB1 levels and clinical conditions of patients tested positive for COVID-19?

Is there a relationship between HMGB1 levels and clinical conditions of patients tested positive for COVID-19?

Increase of HO-1 Expression in Critically Ill COVID-19 Patients Is Associated with Poor Prognosis and Outcome

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study

Contact Info

Product

Resources

About