Research

18 pages, 1559 KiB

Open AccessArticle

A Lysine Residue at the C-Terminus of MHC Class I Ligands Correlates with Low C-Terminal Proteasomal Cleavage Probability

by Adrian Schmalen, Ilona E. Kammerl, Silke Meiners, Elfriede Noessner, Cornelia A. Deeg and Stefanie M. Hauck

Biomolecules 2023, 13(9), 1300; https://doi.org/10.3390/biom13091300 - 24 Aug 2023

Viewed by 1002

Abstract

The majority of peptides presented by MHC class I result from proteasomal protein turnover. The specialized immunoproteasome, which is induced during inflammation, plays a major role in antigenic peptide generation. However, other cellular proteases can, either alone or together with the proteasome, contribute [...] Read more.

The majority of peptides presented by MHC class I result from proteasomal protein turnover. The specialized immunoproteasome, which is induced during inflammation, plays a major role in antigenic peptide generation. However, other cellular proteases can, either alone or together with the proteasome, contribute peptides to MHC class I loading non-canonically. We used an immunopeptidomics workflow combined with prediction software for proteasomal cleavage probabilities to analyze how inflammatory conditions affect the proteasomal processing of immune epitopes presented by A549 cells. The treatment of A549 cells with IFNγ enhanced the proteasomal cleavage probability of MHC class I ligands for both the constitutive proteasome and the immunoproteasome. Furthermore, IFNγ alters the contribution of the different HLA allotypes to the immunopeptidome. When we calculated the HLA allotype-specific proteasomal cleavage probabilities for MHC class I ligands, the peptides presented by HLA-A*30:01 showed characteristics hinting at a reduced C-terminal proteasomal cleavage probability independently of the type of proteasome. This was confirmed by HLA-A*30:01 ligands from the immune epitope database, which also showed this effect. Furthermore, two additional HLA allotypes, namely, HLA-A*03:01 and HLA-A*11:01, presented peptides with a markedly reduced C-terminal proteasomal cleavage probability. The peptides eluted from all three HLA allotypes shared a peptide binding motif with a C-terminal lysine residue, suggesting that this lysine residue impairs proteasome-dependent HLA ligand production and might, in turn, favor peptide generation by other cellular proteases. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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24 pages, 5415 KiB

Open AccessArticle

Effects of GHR Deficiency and Juvenile Hypoglycemia on Immune Cells of a Porcine Model for Laron Syndrome

by Marie-Christin Schilloks, Isabella-Maria Giese, Arne Hinrichs, Lucia Korbonits, Stefanie M. Hauck, Eckhard Wolf and Cornelia A. Deeg

Biomolecules 2023, 13(4), 597; https://doi.org/10.3390/biom13040597 - 26 Mar 2023

Cited by 1 | Viewed by 1993

Abstract

Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) [...] Read more.

Laron syndrome (LS) is a rare genetic disorder characterized by low levels of insulin-like growth factor 1 (IGF1) and high levels of growth hormone (GH) due to mutations in the growth hormone receptor gene (GHR). A GHR-knockout (GHR-KO) pig was developed as a model for LS, which displays many of the same features as humans with LS-like transient juvenile hypoglycemia. This study aimed to investigate the effects of impaired GHR signaling on immune functions and immunometabolism in GHR-KO pigs. GHR are located on various cell types of the immune system. Therefore, we investigated lymphocyte subsets, proliferative and respiratory capacity of peripheral blood mononuclear cells (PBMCs), proteome profiles of CD4⁻ and CD4⁺ lymphocytes and IFN-α serum levels between wild-type (WT) controls and GHR-KO pigs, which revealed significant differences in the relative proportion of the CD4⁺CD8α⁻ subpopulation and in IFN-α levels. We detected no significant difference in the respiratory capacity and the capacity for polyclonal stimulation in PBMCs between the two groups. But proteome analysis of CD4⁺ and CD4⁻ lymphocyte populations revealed multiple significant protein abundance differences between GHR-KO and WT pigs, involving pathways related to amino acid metabolism, beta-oxidation of fatty acids, insulin secretion signaling, and oxidative phosphorylation. This study highlights the potential use of GHR-KO pigs as a model for studying the effects of impaired GHR signaling on immune functions. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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20 pages, 17199 KiB

Open AccessArticle

Potential Biomarkers and Endometrial Immune Microenvironment in Recurrent Implantation Failure

by Fangfang Li, Wenxin Gao, Yanmei Li, Yiqing Wang, Lin Liu and Xuehong Zhang

Biomolecules 2023, 13(3), 406; https://doi.org/10.3390/biom13030406 - 21 Feb 2023

Cited by 2 | Viewed by 1929

Abstract

The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database [...] Read more.

The molecular mechanisms underlying unexplained recurrent implantation failure (RIF) remain unclear. This study aimed at identifying potential biomarkers, exploring relevant signaling pathways, and analyzing the contribution of immune cell infiltration in RIF. Microarray expression datasets were extracted from the Gene Expression Omnibus database to perform bioinformatic analyses. The results showed that ten hub genes may predict RIF with high specificity and sensitivity (area under the curve = 1.000). Protein–protein interaction analysis revealed close interactions between the hub genes and the endometrial receptivity array. The real-time quantitative polymerase chain reaction further validated three potential biomarkers (RAB32, TRIB2, and FAM155B). Functional enrichment analyses indicated that immune pathways were significantly downregulated and lipid metabolism pathways were significantly upregulated in RIF compared with the controls. Significant negative correlations were observed between fatty acid biosynthesis and the immune pathways. Immune cell infiltration, including those in CD56dim natural killer, dendritic, Th1, Th2, and regulatory T cells, as well as macrophages, was significantly reduced in RIF compared with the controls used herein. This study may provide a novel perspective on the diagnosis and treatment of RIF. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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16 pages, 1339 KiB

Open AccessFeature PaperArticle

Monitoring Blood Immune Cells in Patients with Advanced Small Cell Lung Cancer Undergoing a Combined Immune Checkpoint Inhibitor/Chemotherapy

by Dagmar Riemann, Steffi Turzer, Georgi Ganchev, Wolfgang Schütte, Barbara Seliger and Miriam Möller

Biomolecules 2023, 13(2), 190; https://doi.org/10.3390/biom13020190 - 17 Jan 2023

Cited by 4 | Viewed by 1844

Abstract

In this exploratory prospective observational study on 40 small cell lung cancer (SCLC) patients treated with a combination of chemotherapy and immune checkpoint inhibitors, blood immune cells were characterized by multi-color flow cytometry at the baseline and at the third therapy cycle. The [...] Read more.

In this exploratory prospective observational study on 40 small cell lung cancer (SCLC) patients treated with a combination of chemotherapy and immune checkpoint inhibitors, blood immune cells were characterized by multi-color flow cytometry at the baseline and at the third therapy cycle. The numbers of neutrophils and of T-, B-, and NK cells, as well as the frequency of HLA-DR^low monocytes, 6-SulfoLacNAc (slan)+ non-classical monocytes and circulating dendritic cell (DC) subtypes were determined. The prognostic value of the parameters was evaluated by the patient’s survival analysis with overall survival (OS) as the primary endpoint. In addition, blood cell parameters from SCLC patients were compared to those from non-SCLC (NSCLC). The global median OS of patients was 10.4 ± 1.1 months. Disease progression (15% of patients) correlated with a higher baseline neutrophil/lymphocyte ratio (NLR), more HLA-DR^low monocytes, and lower NK cell and DC numbers. The risk factors for poor OS were the presence of brain/liver metastases, a baseline NLR ≥ 6.1, HLA-DR^low monocytes ≥ 21% of monocytes, slan+ non-classical monocytes < 0.12%, and/or CD1c+ myeloid DC < 0.05% of leukocytes. Lymphocytic subpopulations did not correlate with OS. When comparing biomarkers in SCLC versus NSCLC, SCLC had a higher frequency of brain/liver metastases, a higher NLR, the lowest DC frequencies, and lower NK cell numbers. Brain/liver metastases had a substantial impact on the survival of SCLC patients. At the baseline, 45% of SCLC patients, but only 24% of NSCLC patients, had between three and five risk factors. A high basal NLR, a high frequency of HLA-DR^low monocytes, and low levels of slan+ non-classical monocytes were associated with poor survival in all lung cancer histotypes. Thus, the blood immune cell signature might contribute to a better prediction of SCLC patient outcomes and may uncover the pathophysiological peculiarities of this tumor entity. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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16 pages, 3351 KiB

Open AccessArticle

EIF4G1 Is a Potential Prognostic Biomarker of Breast Cancer

by Kun Li, Guangqing Tan, Xin Zhang, Weiyu Lu, Jingyi Ren, Yuewen Si, Enoch Appiah Adu-Gyamfi, Fangfang Li, Yingxiong Wang, Biao Xie and Meijiao Wang

Biomolecules 2022, 12(12), 1756; https://doi.org/10.3390/biom12121756 - 26 Nov 2022

Cited by 3 | Viewed by 2985

Abstract

Background: Breast cancer (BRCA) is one of the most common cancers in women worldwide and a leading cause of death from malignancy. This study was designed to identify a novel biomarker for prognosticating the survival of BRCA patients. Methods: The prognostic potential of [...] Read more.

Background: Breast cancer (BRCA) is one of the most common cancers in women worldwide and a leading cause of death from malignancy. This study was designed to identify a novel biomarker for prognosticating the survival of BRCA patients. Methods: The prognostic potential of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) was assessed using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) as training cohort and validation set, respectively. The functional enrichment analysis of differentially expressed genes (DEGs) was performed. The relationship between EIF4G1 and tumor microenvironment (TME) was analyzed. Immunotherapy responses were explored by the immunophenoscores (IPS) and tumor immune dysfunction and exclusion (TIDE) score. The Connectivity Map (CMap) was used to discover potentially effective therapeutic molecules against BRCA. Immunohistochemistry (IHC) was applied to compare the protein levels of EIF4G1 in normal and cancer tissues and to verify the prognostic value of EIF4G1. Results: BRCA patients with increased expression of EIF4G1 had a shorter overall survival (OS) in all cohorts and results from IHC. EIF4G1-related genes were mainly involved in DNA replication, BRCA metastasis, and the MAPK signaling pathway. Infiltration levels of CD4⁺-activated memory T cells, macrophages M0, macrophages M1, and neutrophils were higher in the EIF4G1 high-expression group than those in the EIF4G1 low-expression group. EIF4G1 was positively correlated with T cell exhaustion. Lower IPS was revealed in high EIF4G1 expression patients. Five potential groups of drugs against BRCA were identified. Conclusion: EIF4G1 might regulate the TME and affect BRCA metastasis, and it is a potential prognostic biomarker and therapeutic target for BRCA. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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10 pages, 1920 KiB

Open AccessArticle

A New Laboratory Workflow Integrating the Free Light Chains Kappa Quotient into Routine CSF Analysis

by Malte Johannes Hannich, Mohammed R. Abdullah, Kathrin Budde, Astrid Petersmann, Matthias Nauck, Alexander Dressel and Marie Süße

Biomolecules 2022, 12(11), 1690; https://doi.org/10.3390/biom12111690 - 15 Nov 2022

Cited by 2 | Viewed by 1130

Abstract

We performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid [...] Read more.

We performed this cohort study to test whether further analysis of intrathecal inflammation can be omitted if the free light chain kappa (FLCκ) quotient is within the reference range in the corresponding quotient diagram. FLCκ concentrations were measured in serum and cerebrospinal fluid (CSF) samples. The intrathecal fraction (IF) of FLCκ was calculated in relation to the hyperbolic reference range. 679 patient samples were used as a discovery cohort (DC). The sensitivity and negative predictive value (NPV) of the FLCκ-IF for the detection of an intrathecal humoral immune response (CSF-specific OCB and/or IF IgG/A/M > 0%) was determined. Based on these data, a diagnostic algorithm was developed and prospectively validated in an independent validation cohort (VC, n = 278). The sensitivity of the FLCκ-IF was 98% in the DC and 97% in the VC with a corresponding NPV of 99%. The use of the FLCκ-IF as a first line analysis would have reduced the Ig and OCB analysis by 62% in the DC and 74% in the VC. The absence of a FLCκ-IF predicts the absence of a humoral intrathecal immune response with a very high NPV of 99%. Thus, integration of our proposed algorithm into routine CSF laboratory analysis could help to reduce analytical efforts. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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17 pages, 3830 KiB

Open AccessArticle

FDCSP Is an Immune-Associated Prognostic Biomarker in HPV-Positive Head and Neck Squamous Carcinoma

by Qingqing Wu, Tingru Shao, Guangzhao Huang, Zenan Zheng, Yingtong Jiang, Weisen Zeng and Xiaozhi Lv

Biomolecules 2022, 12(10), 1458; https://doi.org/10.3390/biom12101458 - 12 Oct 2022

Cited by 4 | Viewed by 1973

Abstract

Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, [...] Read more.

Background: Head and neck squamous carcinoma (HNSC) poses a major threat to human life. The role of human papillomavirus (HPV) infection in the initiation and progression of HNSC is becoming more widely accepted. HPV-positive (HPV+) HNSC has shown unique responses to cancer therapies, which may be due to differences in immune cell infiltration. It is critical to determine how the immune responses to HPV in HNSC are regulated. Methods: Transcriptome data of HNSC from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database were analyzed. Then, the CIBERSORT algorithm was used to calculate immune cell infiltration in HNSC. FDCSP expression level was detected by qPCR in the HNSC tissues collected from the Nanfang Hospital. Results: Follicular dendritic cell secreted protein (FDCSP) was highly expressed in HPV+ HNSC, and higher expression of FDSCP was associated with a favorable prognosis. In HPV+ HNSC samples, FDCSP significantly increased the proportion of T follicular helper cells (TFHs). FDCSP expression was also found to be associated with TP53 mutation status in HPV+ HNSC. The function of FDCSP was intimately connected to chemokine pathways, particularly with the C-X-C motif chemokine ligand 13 (CXCL13). We verified that the high expression of FDCSP in HPV+ HNSC and higher FDCSP is closely related to prognosis in HNSC samples we collected by qPCR. Conclusions: Collectively, these findings may provide fresh evidence that FDCSP is a potential chemokine-associated prognostic biomarker in HPV+ HNSC. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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10 pages, 3508 KiB

Open AccessArticle

Expression of Major Lipid Raft Protein Raftlin in Chronic Rhinosinusitis with Nasal Polyps in Smoking and Non-Smoking Patients Correlated with Interleukin-17 and Tumor Necrosis Factor-α Levels

by Yu-Tsai Lin, Ming-Hsien Tsai, Yan-Ye Su, Wei-Chih Chen, Shun-Chen Huang and Chih-Yen Chien

Biomolecules 2022, 12(9), 1316; https://doi.org/10.3390/biom12091316 - 17 Sep 2022

Cited by 1 | Viewed by 1662

Abstract

Raftlin, as an inflammatory biomarker, has been previously reported in chronic inflammatory diseases. This study investigates the expression of Raftlin in cigarette smokers and in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as evaluating its correlation with interleukin-17 (IL-17) and tumor necrosis [...] Read more.

Raftlin, as an inflammatory biomarker, has been previously reported in chronic inflammatory diseases. This study investigates the expression of Raftlin in cigarette smokers and in chronic rhinosinusitis with nasal polyps (CRSwNP), as well as evaluating its correlation with interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) levels. A total of 30 CRSwNP non-smoking and 16 CRSwNP + SK (smoking) patients undergoing endoscopic sinus surgery were enrolled, while 20 middle turbinate tissue pieces were examined and performed as the control group. In nasal mucosa epithelial staining, Raftlin levels were elevated in the columnar cells and were stained much more intensely in the CRSwNP and CRSwNP + SK groups. Raftlin was located more closely to the apical region of the epithelium in the CRSwNP + SK group; however, the Raftlin levels from whole nasal tissue pieces, according to ELISA data, showed that there was no significant difference between the three different study groups. A positive relationship by Pearson correlation was found between IL-17 or TNF-α levels and Raftlin levels. Taken together, these data indicate that increasing Raftlin expression in columnar cells might involve nasal epithelial remodeling in smokers with CRSwNP. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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13 pages, 2033 KiB

Open AccessArticle

t⁶A and ms²t⁶A Modified Nucleosides in Serum and Urine as Strong Candidate Biomarkers of COVID-19 Infection and Severity

by Yu Nagayoshi, Kayo Nishiguchi, Ryosuke Yamamura, Takeshi Chujo, Hiroyuki Oshiumi, Hiroko Nagata, Hitomi Kaneko, Keiichi Yamamoto, Hirotomo Nakata, Korin Sakakida, Akihiro Kunisawa, Masataka Adachi, Yutaka Kakizoe, Takanori Mizobe, Jun-ichi Kuratsu, Shinya Shimada, Yasushi Nakamori, Masao Matsuoka, Masashi Mukoyama, Fan-Yan Wei and Kazuhito Tomizawa Show full author list Hide full author list

Biomolecules 2022, 12(9), 1233; https://doi.org/10.3390/biom12091233 - 03 Sep 2022

Cited by 3 | Viewed by 2037

Abstract

SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 [...] Read more.

SARS-CoV-2 infection alters cellular RNA content. Cellular RNAs are chemically modified and eventually degraded, depositing modified nucleosides into extracellular fluids such as serum and urine. Here we searched for COVID-19-specific changes in modified nucleoside levels contained in serum and urine of 308 COVID-19 patients using liquid chromatography-mass spectrometry (LC-MS). We found that two modified nucleosides, N⁶-threonylcarbamoyladenosine (t⁶A) and 2-methylthio-N⁶-threonylcarbamoyladenosine (ms²t⁶A), were elevated in serum and urine of COVID-19 patients. Moreover, these levels were associated with symptom severity and decreased upon recovery from COVID-19. In addition, the elevation of similarly modified nucleosides was observed regardless of COVID-19 variants. These findings illuminate specific modified RNA nucleosides in the extracellular fluids as biomarkers for COVID-19 infection and severity. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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7 pages, 523 KiB

Open AccessArticle

Development of Systemic Autoimmune Diseases in Healthy Subjects Persistently Positive for Antiphospholipid Antibodies: Long-Term Follow-Up Study

by Fulvia Ceccarelli, Francesco Natalucci, Giulio Olivieri, Carmelo Pirone, Licia Picciariello, Valeria Orefice, Simona Truglia, Francesca Romana Spinelli, Cristiano Alessandri, Antonio Chistolini and Fabrizio Conti

Biomolecules 2022, 12(8), 1088; https://doi.org/10.3390/biom12081088 - 07 Aug 2022

Cited by 2 | Viewed by 1443

Abstract

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least [...] Read more.

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least two consecutive determinations, for one or more aPL [anti-Cardiolipin (aCL) IgM/IgG, anti-Beta2Glycoprotein I (aB2GPI) IgM/IgG, Lupus Anticoagulant (LA)]. All subjects were evaluated every six months, or in accordance with the patient’s clinical course, in order to record the development of clinical and laboratory features suggestive for sAD. Ninety-five subjects [M/F 20/75, median age at first determination 46 years, Interquartile Range (IQR) 19] were enrolled. Thirty-three subjects (34.7%) were positive for only one aPL [15 (15.8%) for aCL, 15 (15.8%) for LA, and 5 (5.3%) for aB2GPI]; 37 (38.9%) had double positivity [32 (33.6%) for aCL and aB2GPI; 5 (5.3%) for aCL and LA], 23 (24.2%) had triple positivity. We prospectively followed up our cohort for a median period of 72 months (IQR 84). During a total follow-up of 7692 person-months, we found an absolute risk for sAD development equal to 1.8%. Specifically, 14 (14.7%) patients developed a sAD: in four patients (4.2%), after developing a thrombotic event, an antiphospholipid syndrome was diagnosed, 7 (7.4%) patients developed an Undifferentiated Connective Tissue Disease after a median period of 76 months (IQR 75.5), and lastly, three (3.1%) patients could be classified as affected by Systemic Lupus Erythematosus according to the ACR/EULAR 2019 criteria. The presence of triple positivity status resulted in being significantly associated with the progression to sAD (p-value = 0.03). In conclusion, we observed the development of sAD in almost 15% of aPL positive subjects. Triple positivity was significantly associated with this progression, suggesting a possible role as biomarker for this condition. Thus, our results could suggest the need for periodic follow-up for such patients to assess early diagnosis and treatment. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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15 pages, 2900 KiB

Open AccessArticle

NETosis and Nucleosome Biomarkers in Septic Shock and Critical COVID-19 Patients: An Observational Study

by Laure Morimont, Mélanie Dechamps, Clara David, Céline Bouvy, Constant Gillot, Hélène Haguet, Julien Favresse, Lorian Ronvaux, Julie Candiracci, Marielle Herzog, Pierre-François Laterre, Julien De Poortere, Sandrine Horman, Christophe Beauloye and Jonathan Douxfils

Biomolecules 2022, 12(8), 1038; https://doi.org/10.3390/biom12081038 - 27 Jul 2022

Cited by 9 | Viewed by 2535

Abstract

Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to [...] Read more.

Background: Neutrophil extracellular traps’ (NETs’) formation is a mechanism of defense that neutrophils deploy as an alternative to phagocytosis, to constrain the spread of microorganisms. Aim: The aim was to evaluate biomarkers of NETs’ formation in a patient cohort admitted to intensive care unit (ICU) due to infection. Methods: Forty-six septic shock patients, 22 critical COVID-19 patients and 48 matched control subjects were recruited. Intact nucleosomes containing histone 3.1 (Nu.H3.1), or citrullinated histone H3R8 (Nu.Cit-H3R8), free citrullinated histone (Cit-H3), neutrophil elastase (NE) and myeloperoxidase (MPO) were measured. Results: Significant differences in Nu.H3.1 and NE levels were observed between septic shock and critical COVID-19 subjects as well as with controls (p-values < 0.05). The normalization of nucleosome levels according to the neutrophil count improved the discrimination between septic shock and critical COVID-19 patients. The ratio of Nu.Cit-H3R8 to Nu.H3.1 allowed the determination of nucleosome citrullination degree, presumably by PAD4. Conclusions: H3.1 and Cit-H3R8 nucleosomes appear to be interesting markers of global cell death and neutrophil activation when combined. Nu.H3.1 permits the evaluation of disease severity and differs between septic shock and critical COVID-19 patients, reflecting two distinct potential pathological processes in these conditions. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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13 pages, 1233 KiB

Open AccessArticle

SCD14-ST and New Generation Inflammatory Biomarkers in the Prediction of COVID-19 Outcome

by Emanuela Galliera, Luca Massaccesi, Lina Yu, Jianwen He, Marco Ranucci and Massimiliano M. Corsi Romanelli

Biomolecules 2022, 12(6), 826; https://doi.org/10.3390/biom12060826 - 13 Jun 2022

Cited by 3 | Viewed by 1926

Abstract

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study [...] Read more.

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients. Full article

(This article belongs to the Special Issue Immune-Related Biomarkers)

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