P321 Ulcerative colitis: Role of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in predicting disease severity

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

Download Full-text

THE ROLE OF SEVERAL CYTOKINES IN THE PATHOGENESIS OF AUTOIMMUNE INFLAMMATION IN PATIENTS WITH ULCERATIVE COLITIS

10.26226/morressier.59a6b34bd462b80290b559d4 ◽

2017 ◽

Author(s):

Alina Valeeva

Keyword(s):

Ulcerative Colitis ◽

Autoimmune Inflammation

Download Full-text

Faculty Opinions recommendation of Forty-two novel COL7A1 mutations and the role of a frequent single nucleotide polymorphism in the MMP1 promoter in modulation of disease severity in a large European dystrophic epidermolysis bullosa cohort.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1168314.630476 ◽

2009 ◽

Author(s):

Dedee Murrell ◽

Heather Cohn

Keyword(s):

Single Nucleotide Polymorphism ◽

Disease Severity ◽

Epidermolysis Bullosa ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Dystrophic Epidermolysis Bullosa ◽

Mmp1 Promoter

Download Full-text

Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response

Nature Communications ◽

10.1038/s41467-018-07841-3 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 43

Author(s):

Yael Haberman ◽

Rebekah Karns ◽

Phillip J. Dexheimer ◽

Melanie Schirmer ◽

Judith Somekh ◽

...

Keyword(s):

Ulcerative Colitis ◽

Treatment Response ◽

Disease Severity ◽

Underlying Disease

Download Full-text

The Synergistic Role of Diet and Exercise in the Prevention, Pathogenesis, and Management of Ulcerative Colitis: An Underlying Metabolic Mechanism

Nutrition and Metabolic Insights ◽

10.1177/1178638819834526 ◽

2019 ◽

Vol 12 ◽

pp. 117863881983452 ◽

Cited By ~ 1

Author(s):

Jonah Stavsky ◽

Radhashree Maitra

Keyword(s):

Ulcerative Colitis ◽

Aerobic Exercise ◽

Exercise Frequency ◽

Simultaneous Reduction ◽

Diet And Exercise ◽

Literature Reviews ◽

Amino Acid Intake ◽

Metabolic Mechanism ◽

Immunological Research

Ulcerative colitis (UC) is a biologically complex condition characterized by chronic, relapsing inflammation of the gastrointestinal tract. The relative incidence of this debilitating condition is increasing and sociologically damaging outcomes are a continued reality. Several etiological theories for UC are currently under investigation, spanning between genetic and environmental determinants. From an environmental perspective, previous literature reviews have demonstrated the independent effectiveness of specific diet and exercise patterns in modifying UC immuno-pathophysiology. This article explores the synergistic role of diet and aerobic exercise in the prevention, pathogenesis, and management of UC in the context of recent immunological research. Through a unifying mechanism—that is, microbial influence of colonic inflammation and immuno-pathophysiology—the simultaneous reduction of pro-inflammatory dietary sulfurous amino acid intake (ie methionine, cysteine, homocysteine, and taurine) and the upregulation of aerobic exercise frequency (which spurs the colonization of anti-inflammatory butyrate, acetate, and propionate producing microbial taxa) demonstrate the clinical efficacy of incorporating both diet and exercise modifications for UC prevention and management through pathogenic alterations.

Download Full-text

The Abstruse Side of Type I Interferon Immunotherapy for COVID-19 Cases with Comorbidities

Journal of Respiration ◽

10.3390/jor1010005 ◽

2021 ◽

Vol 1 (1) ◽

pp. 49-59

Author(s):

Selvakumar Subbian

Keyword(s):

Infectious Diseases ◽

Disease Severity ◽

Type I Interferon ◽

Host Factors ◽

Type I ◽

The Novel ◽

Inflammatory Drugs ◽

Precautionary Measures ◽

Inducible Genes

The Coronavirus Disease-2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed 1.2 million people globally since December 2019. Although the host factors underpinning COVID-19 pathology are not fully understood, type I interferon (IFN-I) response is considered crucial for SARS-CoV-2 pathogenesis. Perturbations in IFN-I signaling and associated interferon-inducible genes (ISG) are among the primary disease severity indicators in COVID-19. Consequently, IFN-I therapy, either alone or in- combination with existing antiviral or anti-inflammatory drugs, is tested in many ongoing clinical trials to reduce COVID-19 mortality. Since signaling by the IFN-I family of molecules regulates host immune response to other infectious and non-infectious diseases, any imbalance in this family of cytokines would impact the clinical outcome of COVID-19, as well as other co-existing diseases. Therefore, it is imperative to evaluate the beneficial-versus-detrimental effects of IFN-I immunotherapy for COVID-19 patients with divergent disease severity and other co-existing conditions. This review article summarizes the role of IFN-I signaling in infectious and non-infectious diseases of humans. It highlights the precautionary measures to be considered before administering IFN-I to COVID-19 patients having other co-existing disorders. Finally, suggestions are proposed to improve IFN-I immunotherapy to COVID-19.

Download Full-text

THE ROLE OF MYELOPEROXIDASE AND NEUTROPHIL EXTRACELLULAR TRAPS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.009 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S4-S4

Author(s):

Belal Chami ◽

Gulfam Ahmad ◽

Angie Schroder ◽

Patrick San Gabriel ◽

Paul Witting

Keyword(s):

Disease Severity ◽

Hypochlorous Acid ◽

Tissue Injury ◽

Activity Index ◽

Critical Role ◽

Neutrophil Migration ◽

Sodium Sulphate ◽

Host Tissue ◽

Neutrophil Extracellular Trap

Abstract Neutrophils are short-lived immune cells that represent the major cell type recruited to the inflamed bowel releasing their azurophilic granules containing enzymes myeloperoxidase (MPO). Fecal and serum MPO levels has previously been shown to correlate to disease severity in IBD patients. MPO, in the presence of H2O2 and free Cl- undergoes a halogenation cycle, yielding the two-electron oxidant, hypochlorous acid (HOCl) - a potent bactericidal agent. However, chronic intestinal exposure to MPO/HOCl due to perpetual inflammation may cause secondary host-tissue injury and cell death. Neutrophil Extracellular Trap (NET)osis is a specialised form of neutrophil death where MPO is entrapped in a DNA scaffold and continues to elicit HOCl activity and may further contribute to host-tissue injury. We investigated the presence of NETs in surgically excised ileum samples from CD and healthy patients using advanced confocal microscopic techniques and found MPO, Neutrophil Elastase (NE) and Citrullinated Histone h3 (CitH3) - critical components of NET formation, individually positively correlate to the severity of histopathological intestinal injury. Furthermore, multiplex Opal™ IHC performed using LMS880 Airyscan-moduled microscopy with z-stacking revealed colocalization of NE, MPO, CitH3 and DAPI indicating the extensive presence of NETs in severely affected CD tissue. Using two pharmacological inhibitors of MPO in a dextran sodium sulphate (DSS) model of murine colitis, we demonstrated the pathological role of MPO in experimental colitis. MPO inhibitors, TEMPOL and AZD3241 delivered via daily i.p significantly rescued the course of colitis by abrogating clinical indices including body weight loss, disease activity index, inhibiting serum peroxidation, and preserving colon length, while significantly mitigating histoarchitectural damage associated with DSS-induced colitis. We also showed that MPO inhibition decreased neutrophil migration to the gut, suggesting MPO may play a role in perpetuating the inflammatory cell by further recruiting cells to the inflamed gut. Collectively, we have shown for the first time that MPO is not only an important clinical marker of disease severity but may also play a critical role in perpetuating host-tissue damage and inflammation.

Download Full-text