tiprelestat (SKALP) / tiakis Biotech - LARVOL DELTA

A Multicenter Validation of a Fully Automated Chemiluminescence Immunoassay for Plasma Elafin in Psoriasis Diagnosis and Severity Assessment. (PubMed, Adv Sci (Weinh)) - "It effectively distinguishes disease severity (AUC 0.68 mild vs moderate; 0.77 moderate vs severe), and Elafin levels correlated with treatment duration in moderate (R = 0.51) and severe (R = 0.41) cases. This CLIA reagent kit demonstrates excellent analytical and clinical performance, supporting automated, high-throughput Elafin detection as a reliable tool for diagnosing and managing moderate-to-severe psoriasis."

Journal • Dermatology • Dermatopathology • Immunology • Psoriasis

Tiprelestat for treatment of hospitalized COVID-19: results of the double-blind randomized placebo-controlled COMCOVID trial. (PubMed, Adv Ther) - P1/2 | "Tiprelestat infused for 30 min twice daily in patients with moderate COVID-19 requiring hospitalization was well tolerated and appears to be safe. Beneficially, plasma trough levels of the drug over time were high and stable. The small sample size does not facilitate reliable statements about efficacy. Further studies are necessary including other inflammatory severe respiratory diseases."

Clinical • Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • ELANE

Serum Elafin and Vascular Affection in Behcet Disease (clinicaltrials.gov) - P=N/A | N=90 | Not yet recruiting | Sponsor: Assiut University

New trial • Immunology

Phase I Clinical Trial of CK0801 (cord blood regulatory T cells) in Patients with Bone Marrow Failure Syndrome (BMF) Including Aplastic Anemia, Myelodysplasia and Myelofibrosis (ASH 2019) - P1; "Serum will be analyzed for inflammatory cytokines: IL1, IL2, IL4, IL6, IL7, IL8, IL10, IL17, IFN-gamma, ST2, REG3a, OPN, Follistatin, Elafin, TGF-beta. Optional exploratory cytokines: SCF, G-CSF, GM-CSF, HGF, VEGF, SDF1a, MCP1, MCP2, TARC, MIP3a, TECK, CTACK, CCL28, FGF, PDGF, EGF, TGF-α, TLR. The first patient is already consented with a planned total of 9 patients."

Clinical • P1 data • CSF2 • CSF3 • CXCL8 • HGF • IFNG • IL10 • IL15 • IL17A • IL2 • IL4 • IL6 • IL7 • REG3A • VEGFA

Plasma Biomarker Association with Response in Acute GVHD Subjects Treated with the Combination of Itacitinib and Corticosteroids in a Phase 1 Clinical Trial (ASH 2018) - P1; "In this study, we compared the plasma levels of ST2, REG3A, TNFR1, and Trappin-2/Elafin in order to distinguish response to combination treatment. Proteomic analysis of clinical samples confirmed the value of ST2 and TNFR1 in predicting response to treatment with itacitinib and steroids and also identified a number of novel plasma biomarkers that may have utility in selecting and/or monitoring aGVHD subjects when treated with a combination of corticosteroids and itacitinib."

Biomarker • Clinical • P1 data • Biosimilar • Graft versus Host Disease • Transplantation

Combination of IL-17A/F and TNF-α uniquely alters the bronchial epithelial cell proteome to enhance proteins that augment neutrophil migration. (PubMed, J Inflamm (Lond)) - "This study identifies proteins and signaling mediated by concurrent IL-17A/F and TNF-α exposure in the lungs, relevant to respiratory diseases characterized by chronic inflammation, especially neutrophilic airway inflammation such as severe asthma."

Journal • Asthma • Immunology • Inflammation • Oncology • Pneumonia • Pulmonary Disease • Respiratory Diseases • CXCL8 • IL17A • LCN2 • TNFA

Subcutaneous Elafin in Healthy Subjects (clinicaltrials.gov) - P1; N=30; Completed; Sponsor: Roham T. Zamanian; Active, not recruiting ➔ Completed; Trial completion date: Jul 2020 ➔ Nov 2020

Clinical • Trial completion • Trial completion date • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Elafin as a Predictive Biomarker of Acute Skin Graft-Versus-Host Disease After Haploidentical Stem Cell Transplantation Using Post-Transplant High-Dose Cyclophosphamide. (PubMed, Front Immunol) - "Of note, patients with higher elafin plasma levels at day +15 presented a higher incidence of stage III-IV skin aGVHD (HR = 18.9; p < 0.001). These results were confirmed (HR = 20.6; p < 0.001) in an independent group of patients (n = 62), i.e. the "validation cohort." These data suggest that measurement of elafin in patients undergoing haplo-HSCT with PTCy might be useful for an early identification of those patients who are at higher risk of suffering severe skin aGVHD and thus, improve their treatment and prognosis."

Biomarker • Journal • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation • ELANE

Transglutaminase 2 as a Marker for Inflammation and Therapeutic Target in Sepsis. (PubMed, Int J Mol Sci) - "Based on these findings and recently published research, we have reviewed the current understanding of the relationship between TG2 and sepsis. Following the genetic and pharmacological inhibition of TG2, we also assessed the evidence regarding the use of TG2 as a potential marker and therapeutic target in inflammation and sepsis."

Journal • Review • Hepatology • Immunology • Infectious Disease • Inflammation • Septic Shock

Molecular structure, gene expression and functional role of WFDC1 in angiogenesis and cancer. (PubMed, Cell Biochem Funct) - "The WAP four-disulphide core domain protein 1 (WFDC1) gene (also called PS20), encodes the 20 kDa prostate stromal protein (ps20), which is a member of the WAP-type four-disulphide core domain family of proteins, and exhibits characteristics of serine protease inhibitors, such as elafin and secretory leukocyte protease inhibitor...In addition, it was involved in the modulation of memory T cells during human immunodeficiency virus infection. Gaining a solid understanding of the mechanisms by which WFDC1 regulates tissue homeostasis and disease processes, in a tissue specific manner, will be an important move towards the development of WFDC1/ps20 as potential therapeutic targets."

Journal • Review • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Oncology

[VIRTUAL] Acute sexual violence exposure dysregulates HIV associated cervical immune biomarkers in women (HIVR4P 2021) - "ELISA was used to analyze protective/anti-inflammatory/HIV inhibitory biomarkers Serpin A1, Elafin, Secretory Leukocyte Protease Inhibitor (SLPI), and Human Beta-Defensin-2 (HBD2) and inflammatory cytokines/chemokines IL6, IL1b, IL1a, TNFa, MIP3a, IL8, and IP10... Our data points to immune dysregulation in the female genital tract following exposure to acute sexual violence, which has the potential to increase HIV risk in this population."

Biomarker • Clinical • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Women's Health • CXCL8 • IL1A • IL1B • IL6 • TNFA

[VIRTUAL] Effects of continued Progestin-based contraceptive usage in the adolescent genital tract: implications for HIV acquisition (HIVR4P 2021) - "Vaginal secretions were tested for pro-inflammatory (IL-1a, IL-1b, TNFa, IL-6, IL-8, MIP-3a,) and anti-inflammatory/anti-HIV (Serpin-A1, Elafin, Beta-Defensin-2) immune mediators using ELISA... Our study demonstrated that the genital immune milieu in adolescent girls was not significantly altered by 3-months of use of any of the progestin-based contraceptives investigated. Additionally, we show feasibility of research in this population which highlights the need for future studies with larger sample size and longer follow-up to evaluate safe and effective contraceptives in adolescent girls."

Human Immunodeficiency Virus • Infectious Disease • Long-acting Reversible Contraceptives • CXCL8 • IL1A • IL1B • IL6 • TNFA

[VIRTUAL] Detecting 24 Kinds of Cytokines Via Flow Cytometry Aimplex Kit Is an Effective Way to Monitor CRS after CAR-T Cells Infusion (ASH 2020) - " A two tubes panel was designed to detect 24 cytokines, including IFN-γ/IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β, and sCD25/GM-CSF/IL-15/MCP-1/GranzymeB/Reg3A/ST2/TNFRSF1A/Elafin/MIP-1 alpha... Detecting 24 kinds of cytokines by Aimplex kit is a promising method, which is time and specimens saving, and can cost-effectively reflect the cytokine situation in PBs from patients post-CAR-T treatment. Increasing the sample size and establishing a cytokines database will be helpful for monitoring, early prevention and control of side effects after CAR-T treatment."

CAR T-Cell Therapy • IO Biomarker • CCL3 • CD8 • CSF2 • CXCL8 • GZMB • IFNG • IL10 • IL15 • IL17A • IL1B • IL2 • IL4 • IL5 • IL6 • REG3A • TNFA

Evaluation of Elafin Immunohistochemical Expression as Marker of Cervical Cancer Severity. (PubMed, Acta Cytol) - "Our results suggest that PI3/Elafin levels and subcellular localization may be used as a biomarker for CC severity."

Journal • Cervical Cancer • Infectious Disease • Oncology • Solid Tumor

New Approaches to Skin Photodamage Histology - Differentiating 'good' versus 'bad' Elastin. (PubMed, J Cosmet Dermatol) - "and conclusion A combination of Movat, fibrillin, elafin and versican for elastogenesis and reversal of solar elastosis. CD44 for HA status (mainly epidermal) and Herovici stain for identifying early collagenesis in the ECM, appears to offer an ideal collection of stains for identifying regenerative events within the skin layers."

Journal • CD44 • VCAN

Predictive value of cervical cytokine, antimicrobial and microflora levels for pre-term birth in high-risk women. (PubMed, Sci Rep) - "There were no differences in elafin or human beta defensin-1 protein levels between the two groups. Multiple bacterial species were detected in a higher proportion of women who delivered preterm than in those who delivered at term (P = 0.005). Cervical fluid IL-8 and IL-1β and microflora have the potential to be used as biomarkers to predict sPTB in high risk women."

Biomarker • Clinical • Journal

[VIRTUAL] Serum elafin as a potential marker for the diagnosis and assessment of disease activity in Behçet's disease (EADV 2020) - No abstract available

[VIRTUAL] Localization of Upregulated Proteins in Hidradenitis Suppurativa (SHSA 2020) - "Our findings reveal the antimicrobial and structural proteins that are more abundant in HS skin are expressed at different locations in HS skin compared to control skin. Additionally, the expression pattern of OAS2, psoriasin, koebnerisin, elafin, and OASL in non-healing sinus tracts in HS further highlights the link between chronic wounds and HS. Our findings add to the growing knowledge of the pathological changes associated with HS."

Dermatology • Hidradenitis Suppurativa • Inflammation

[VIRTUAL] Expression of antimicrobial peptides in lesional keratinocytes of patients with HS (SHSA 2020) - "Gene expression of the following AMPs was analyzed by quantitative RT-PCR: hBD-2, LL37, RNAse 7, psoriasin and SKALP (Elafin)... In HS keratinocytes expression of hBD-2 und psoriasin is stimulated only with Pam2CSK4 but not with MDP. The lack of stimulation with MDP is remarkable, as it represents a constituent of the bacterial cell wall and thus a common pathogen-associated molecular pattern (PAMP). It may be related to the impaired control of commensal bacteria, potentially contributing to the pathogenesis of HS."

Clinical • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • CXCL8 • IL6 • TNFA

[VIRTUAL] SAFETY OF BIFIDOBACTERIUM LONGUM NCC 2705 AND PRODUCTION OF ITS SERPIN IN PATIENTS WITH CELIAC DISEASE AND NON-CELIAC GLUTEN SENSITIVITY (UEGW 2020) - "Expression of the human serine protease inhibitor elafin is decreased in the duodenum of CeD patients [1]... BL NCC2705 is well tolerated and safe for human consumption. The appearance of BL NCC2705 in duodenal aspirates is associated with a concomitant increase in serpin concentration. This provides a mechanistic basis for the potential use of BL NCC2705 as adjuvant treatment to GFD to protect from accidental gluten intake."

Clinical • Allergy • Celiac Disease • Gastrointestinal Disorder • Immunology

[VIRTUAL] THE ANTI-INFLAMMATORY AND ANTIMICROBIAL ELAFIN SYNERGIZES WITH IL-6 TO INDUCE M2 MACROPHAGES, WHICH PROTECT MICE WHEN ADOPTIVELY TRANSFERRED DURING PSEUDOMONAS AERUGINOSA LUNG INFECTIONS (NACFC 2020) - "Our study demonstrates that AMs genetically modified ex vivo with IL-6 and the anti-inflammatory molecule elafin provide protection when administered in lungs of mice infected with P.a, by conferring a local regulatory/anti-inflammatory phenotype. This study strenghthens the idea that gene/cell transfer therapy aiming at reinforcing the anti-inflammatory/repairing phenotype could benefit cystic fibrosis patients, in addition to the already successful corrector/potentiator strategies currently in use."

Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Inflammation • Respiratory Diseases • ELANE • IL10 • IL4R • IL6

Concerted actions by MMPs, ADAMTS and serine proteases during remodeling of the cartilage callus into bone during osseointegration of hip implants. (PubMed, Bone Rep) - "Plasma was analyzed for MMP-1, -2, -3, -8, -9, -10, -13, -14, tissue inhibitor of metalloproteinase (TIMP)-1, -2, -3, ADAMTS4, ADAMTS5, the serine proteases neutrophil elastase (NE), proteinase 3 (PR3) and their endogenous inhibitors, secretory leucocyte proteinase inhibitor (SLPI), trappin-2/elafin and serpina1 (α-1 antitrypsin)...Regulation and fine-tuning of cartilage remodeling by MMPs and ADAMTS is controlled by TIMP-3 whereas serine proteases are regulated by serpina1. Increased MMP-1 and MMP-9 beyond 10Y post-THA support a role during coupled bone remodeling."

Journal • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology

Gene expression in urinary incontinence and pelvic organ prolapse: a review of literature. (PubMed, Curr Opin Obstet Gynecol) - "The current review highlights many genes which are potential biomarkers and targets for drug development."

Journal • Overactive Bladder • Urinary Incontinence • Urology • APOE • Collagen Type IV • CTNNB1 • ER • MMP9 • RASGRP1 • SLPI • STAT3

Evolution of pathogenetic therapy of pulmonary arterial hypertension (PubMed, Ter Arkh) - "The available results of these studies allow to suggest the inclusion to clinical guidelines several new drugs for the pathogenetic treatment of PAH in the near future: receptor tyrosine kinase inhibitors, Rho - kinase inhibitors, immunosuppressants and type 2 activin receptor agonists, protein kinase C inhibitors, aromatase inhibitors and estrogen receptor antagonists, poly-(ADP-ribose)-polymerase inhibitors and bromodomain protein 4, elastase inhibitors. Some of the drugs have already passed the III phase of clinical trials (imatinib), others are at the preclinical stage or at the I-II phase tests (olaparib, enzastaurin, elafin)."

Journal • Gene Therapies • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Portal Hypertension • Pulmonary Arterial Hypertension

A panel of 4 biomarkers for the early diagnosis and therapeutic efficacy of aGVHD. (PubMed, JCI Insight) - "In addition, patients with severe aGVHD showed increased IL-6, TLR4, TNF receptor 1 (TNFR1), and Elafin and decreased TGF-β. TLR4 and TNFR1 were significantly increased in steroid-refractory aGVHD patients compared with steroid-effective patients (P < 0.05).CONCLUSIONA combination of TLR4, TNFR1, TGF-β, and Elafin could be a new 4-biomarker panel to assist aGVHD diagnosis, grading, and evaluation of steroid sensitivity for clinical aGVHD patients.TRIAL REGISTRATIONChiCTR1900022292 "Clinical Research of Umbilical Cord-Derived Mesenchymal Stromal Cells in the Prophylaxis of Graft-Versus-Host Disease After HLA-Haploidentical Stem-Cell Transplantation."FUNDINGNational Key Research Program, National Natural Science Foundation of China, Chongqing Social Career and People's Livelihood Security Science and Technology Innovation Project, Fundamental and Frontier Research Program of Chongqing, and Foundation of Xinqiao Hospital."

Biomarker • Clinical • Journal • Graft versus Host Disease • Hematological Disorders • Transplantation