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Immunology Letters Jul 2020Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life....
BACKGROUND
Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life. Notch signaling has an important role in the development of hematopoietic stem cells and their differentiation to committed lineages, as well as in the regulation of several non-hematopoietic cell lines.
OBJECTIVE
As Notch signaling has been implicated in various inflammatory and autoimmune diseases, it is of interest to elucidate what role do Notch receptors and ligands have in inflammatory arthritides.
METHODS
We performed a search on the role of Notch receptors (1-4) and Notch ligands Delta-like (DLL) 1, 3, 4 and Jagged (Jag) 1 and 2 in animal models of inflammatory arthritis and most common types of human inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis). The initial search identified 135 unique articles, of which 24 were ultimately deemed relevant and included in this systematic review.
RESULTS
Overall, identified articles describe roles for Notch ligands and receptors in inflammatory arthritis, with Notch activation resulting in enhanced Th1/17 polarization, osteoclast differentiation, macrophage activation and fibroblast-like synoviocyte proliferation. However, the inhibitory role of Notch signaling, especially by Jag1 is also described.
CONCLUSION
There is evidence that Notch pathway activation affects multiple cell lineages present within the arthritic environment, therefore potentially acting as one of the drivers of disease pathogenesis. Since cell lineage-selective transgenic mouse models and specific Notch receptor inhibitors are becoming increasingly available, it can be expected that future research will evaluate whether Notch signaling components initiate crucial pathogenic impulses and, therefore, present viable therapeutic targets in inflammatory arthritis.
Topics: Animals; Arthritis; Cell Differentiation; Disease Models, Animal; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Osteoclasts; Receptors, Notch; Serrate-Jagged Proteins; Th1 Cells; Th17 Cells
PubMed: 32325090
DOI: 10.1016/j.imlet.2020.04.010 -
Journal of Pediatric Hematology/oncology Aug 2017Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is a rare and potentially fatal complication of Kawasaki disease (KD)....
Macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, is a rare and potentially fatal complication of Kawasaki disease (KD). We report 2 cases, performed a literature search, and analyze the characteristics of MAS associated with KD. A total of 69 patients were evaluated, 34 reported the date of the diagnosis of MAS and KD, 6% had a diagnosis of MAS before KD, 21% had a simultaneous presentation, and 73% had the diagnosis of MAS after KD. Different treatment approaches were observed with corticosteroids administered in 87%, cyclosporine in 49%, etoposide (VP-16) in 39%, and monoclonal anti-TNF in 6% of cases. Coronary abnormalities were especially high in this group of patients (46%) and 9 patients died (13%). The persistence of fever with splenomegaly, hyperferritinemia, thrombocytopenia, and elevated aspartate aminotransferase (AST) should prompt the consideration of MAS complicating KD.
Topics: Adolescent; Adrenal Cortex Hormones; Antibodies, Monoclonal; Aspartate Aminotransferases; Child; Child, Preschool; Coronary Vessel Anomalies; Cyclosporine; Etoposide; Female; Fever; Humans; Infant; Macrophage Activation Syndrome; Male; Mucocutaneous Lymph Node Syndrome; Tumor Necrosis Factor-alpha
PubMed: 28562511
DOI: 10.1097/MPH.0000000000000872 -
PloS One 2019HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and...
HIV and pneumonia infections have both been shown to negatively impact lung function. However, evidence of the role of inflammation on lung dysfunction in HIV and pneumonia co-infected individuals remains limited. We aimed to systematically review the association of inflammatory markers and lung abnormalities in HIV and pneumonia co-infected individuals. This systematic review was registered with the International Prospective Register of Systematic Reviews on August 15, 2017 (registration number CRD42017069254) and used 4 databases (Cochrane Central Register of Controlled Trials, PubMed Central, Clinical Trials.gov and Google Scholar). All clinical trial, observational, and comparative studies targeting adult (> 18 years old) populations with HIV, pneumonia, or both, that report on immune response (cytokine, chemokine, or biomarker), and lung abnormality as an outcome were eligible. Data selection, risk of bias and extraction were performed independently by 2 blinded reviewers. Due to heterogeneity among the articles, a qualitative synthesis was performed. Our search strategy identified 4454 articles of which, 7 met our inclusion criteria. All of the studies investigated the ability of circulating biomarkers to predict lung damage in HIV. None of the articles included patients with both HIV and pneumonia, nor pneumonia alone. Markers of inflammation (IL-6, TNF-α, CRP), innate defense (cathelicidin), monocyte and macrophage activation (sCD14, sCD163 and, IL-2sRα), endothelial dysfunction (ET-1) and general immune health (CD4/CD8 ratio) were associated with lung abnormalities in HIV. This review highlights the lack of available information regarding the impact of inflammatory mediators on lung function in HIV and pneumonia populations, therefore opportunities to prevent lung damage with available anti-inflammatory treatment or to investigate new ones still remain.
Topics: HIV; HIV Infections; Humans; Inflammation Mediators; Respiratory System Abnormalities
PubMed: 31830103
DOI: 10.1371/journal.pone.0226347 -
Brain Sciences May 2022: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between... (Review)
Review
: Ever since the discovery of tumor-associated immune cells, there has been growing interest in the understanding of the mechanisms underlying the crosstalk between these cells and tumor cells. A "seed and soil" approach has been recently introduced to describe the glioblastoma (GBM) landscape: tumor microenvironments act as fertile "soil" and interact with the "seed" (glial and stem cells compartment). In the following article, we provide a systematic review of the current evidence pertaining to the characterization of glioma-associated macrophages and microglia (GAMs) and microglia and macrophage cells in the glioma tumor microenvironment (TME). An online literature search was launched on PubMed Medline and Scopus using the following research string: "((Glioma associated macrophages OR GAM OR Microglia) AND (glioblastoma tumor microenvironment OR TME))". The last search for articles pertinent to the topic was conducted in February 2022. The search of the literature yielded a total of 349 results. A total of 235 studies were found to be relevant to our research question and were assessed for eligibility. Upon a full-text review, 58 articles were included in the review. The reviewed papers were further divided into three categories based on their focus: (1) Microglia maintenance of immunological homeostasis and protection against autoimmunity; (2) Microglia crosstalk with dedifferentiated and stem-like glioblastoma cells; (3) Microglia migratory behavior and its activation pattern. Aggressive growth, inevitable recurrence, and scarce response to immunotherapies are driving the necessity to focus on the GBM TME from a different perspective to possibly disentangle its role as a fertile 'soil' for tumor progression and identify within it feasible therapeutic targets. Against this background, our systematic review confirmed microglia to play a paramount role in promoting GBM progression and relapse after treatments. The correct and extensive understanding of microglia-glioma crosstalk could help in understanding the physiopathology of this complex disease, possibly opening scenarios for improvement of treatments.
PubMed: 35741603
DOI: 10.3390/brainsci12060718 -
American Journal of Reproductive... Apr 2017Endometriosis is a chronic inflammatory disease associated with an impairment in immune response. Disorders in the peritoneal fluid and ectopic endometrium macrophage... (Review)
Review
PROBLEM
Endometriosis is a chronic inflammatory disease associated with an impairment in immune response. Disorders in the peritoneal fluid and ectopic endometrium macrophage populations and their secretory products create a specific microenvironment inducing the development of the disease. The important factors involved in inflammation associated with endometriosis are chemokines, especially interleukin (IL)-8. For this reason, the current study briefly reviews the role of IL-8 in the pathogenesis of endometriosis.
METHOD OF STUDY
A systematic review was done on all published studies that compared IL-8 expression and concentration in patients with and without endometriosis to evaluate their potential as biomarkers for the disease.
RESULTS
IL-8 induces chemotaxis of neutrophils and other immune cells; also, it is a potent angiogenic agent. Most researchers pointed to the increased peritoneal and serum IL-8 levels and showed correlation with the severity of the disease, size and number of the active lesions. IL-8 takes part in all processes during the development of the disease: adhesion, invasion, and implantation of ectopic tissue. Additionally, the chemokine plays a role in growth and maintenance of ectopic endometrial tissue directly affecting endometrial cell proliferation. IL-8 might also protect ectopic cells against death by apoptosis.
CONCLUSION
It may act as an autocrine growth factor in the endometrium and promotes the vicious circle of endometrial cell attachment and, in consequence, may lead to a transformation from acute to chronic inflammation stage.
Topics: Biomarkers; Cellular Microenvironment; Endometriosis; Female; Humans; Interleukin-8; Peritoneum
PubMed: 28120482
DOI: 10.1111/aji.12622 -
Clinical Chemistry and Laboratory... May 2023The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic... (Meta-Analysis)
Meta-Analysis Review
The SARS-CoV-2 infection is characterized by both systemic and organ hyper-thromboinflammation, with a clinical course ranging from mild up-to critical systemic dysfunction and death. In patients with coronavirus disease 2019 (COVID-19) the monocyte/macrophage population is deeply involved as both trigger and target, assuming the value of useful diagnostic/prognostic marker of innate cellular immunity. Several studies correlated morphological and immunophenotypic alterations of circulating monocytes with clinical outcomes in COVID-19 patients, concluding that monocyte distribution width (MDW) may retain clinical value in stratifying the risk of disease worsening. Through an electronic search in Medline and Scopus we performed an updated literature review and meta-analysis aimed to explore the association between increased MDW levels and illness severity in COVID-19 patients, deciphering role(s) and function(s) of monocytes in the harmful network underlining SARS-CoV-2 infection. We found that significantly elevated MDW values were frequently present in COVID-19 patients who developed unfavorable clinical outcomes, compounded by a significant association between monocyte anisocytosis and SARS-CoV-2 outcomes. These findings suggest that blood MDW index and its scatter plot could represent useful routine laboratory tools for early identification of patients at higher risk of unfavorable COVID-19 and for monitoring the progression of viral infection, clinical outcomes, and therapeutic efficacy throughout hospitalization. According to this evidence, therapeutic decisions in patients with SARS-CoV-2 infection could benefit from monitoring MDW value, with administration of drugs limiting thrombo-inflammation due to monocyte hyper-activation in patients with severe/critical COVID-19 disease.
Topics: Humans; COVID-19; Monocytes; SARS-CoV-2; Inflammation; Thrombosis
PubMed: 36626568
DOI: 10.1515/cclm-2022-0936 -
Human Reproduction Update Jan 2021Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health...
BACKGROUND
Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health and quality of life of women. Histologically, it is defined as the presence of ectopic endometrial islets within the myometrium. Its pathogenesis has not yet been elucidated and several pieces of the puzzle are still missing. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. Here, we review current knowledge on the immunological changes in adenomyosis, with the aim of further elucidation of the pathogenesis of this disease.
OBJECTIVE AND RATIONALE
The objective was to systematically review the literature regarding the role of the immune system in development of adenomyosis in the inner and the outer myometrium, in humans.
SEARCH METHODS
A systematic review of published human studies was performed in MEDLINE, EMBASE and Cochrane Library databases from 1970 to February 2019 using the combination of Medical Subject Headings (MeSH): Adenomyosis AND ('Immune System' OR 'Gonadal Steroid Hormones'), and free-text terms for the following search terms (and their variants): Adenomyosis AND (immunity OR immune OR macrophage OR 'natural killer cell' OR lymphocyte* OR leucocyte* OR HLA OR inflammation OR 'sex steroid' OR 'epithelial to mesenchymal transition' OR 'EMT'). Studies in which no comparison was made with control patients, without adenomyosis (systemic sample and/or eutopic endometrium), were excluded.
OUTCOMES
A total of 42 articles were included in our systematic review. Changes in innate and adaptive immune cell numbers were described in the eutopic and/or ectopic endometrium of women with adenomyosis compared to disease-free counterparts. They mostly described an increase in lymphocyte and macrophage cell populations in adenomyosis eutopic endometrium compared to controls. These observations underscore the immune contributions to the disease pathogenesis. Thirty-one cytokines and other markers involved in immune pathways were studied in the included articles. Pro-inflammatory cytokines (interleukin (IL) 6, IL1β, interferon (IFN) α, tumor necrosis factor α, IFNγ) as well as anti-inflammatory or regulatory mediators (IL10, transforming growth factor β…) were found to be elevated in the eutopic endometrium and/or in the ectopic endometrium of the myometrium in women with adenomyosis compared to controls. Moreover, in women affected by adenomyosis, immunity was reported to be directly or indirectly linked to sex steroid hormone aberrations (notably changes in progesterone receptor in eutopic and ectopic endometrium) in three studies and to EMT in four studies.
WIDER IMPLICATIONS
The available literature clearly depicts immunological changes that are associated with adenomyosis. Both systemic and local immune changes have been described in women affected by adenomyosis, with the coexistence of changes in inflammatory as well as anti-inflammatory signals. It is likely that these immune changes, through an EMT mechanism, stimulate the migration of endometrial cells into the myometrium that, together with an endocrine imbalance, promote this inflammatory process. In light of the considerable impact of adenomyosis on women's health, a better understanding of the role played by the immune system in adenomyosis is likely to yield new research opportunities to better understand its pathogenesis.
Topics: Adenomyosis; Endometriosis; Endometrium; Epithelial-Mesenchymal Transition; Female; Humans; Myometrium; Quality of Life
PubMed: 33099635
DOI: 10.1093/humupd/dmaa038 -
Arthritis Research & Therapy Jul 2016Diagnosing systemic juvenile idiopathic arthritis (SJIA) can be extremely challenging if typical arthritis is lacking. A variety of biomarkers have been described for... (Review)
Review
BACKGROUND
Diagnosing systemic juvenile idiopathic arthritis (SJIA) can be extremely challenging if typical arthritis is lacking. A variety of biomarkers have been described for the diagnosis and management of SJIA. However, very few markers have been well-validated. In addition, increasing numbers of biomarkers are identified by high throughput or multi-marker panels.
METHOD
We identified diagnostic or prognostic biomarkers by systematic literature review, evaluating each according to a predefined level of verification, validation or clinical utility. Diagnostic biomarkers were those identifying SJIA versus (1) non-SJIA conditions or healthy controls (HC) or (2) other non-systemic JIA subtypes. Prognostic biomarkers were those specifically tested for the prediction of (1) disease flare, (2) increased disease activity +/- discrimination of active versus inactive disease, or (3) macrophage activation syndrome (MAS).
RESULTS
Fifty-five studies fulfilled the inclusion criteria identifying 68 unique biomarkers, of which 50/68 (74 %) were investigated by only a single research group. Candidate marker verification and clinical utility was evaluated according to whether markers were readily and reliably measurable, investigated by independent study groups, discovered by more than one method (i.e. verified markers) and validated in independent cohorts. This evaluation revealed diagnostic biomarkers of high interest for further evaluation in the diagnostic approach to SJIA that included heme oxygenase-1, interleukin-6 (IL-6), IL-12, IL-18, osteoprotegerin, S100 calcium-binding protein A12 (S100A12) and S100A8/A9.
CONCLUSION
In summary, a number of biomarkers were identified, though most had limited evidence for their use. However, our findings combined with the identified studies could inform validation studies, whether in single or multi-marker assays, which are urgently needed.
Topics: Arthritis, Juvenile; Biomarkers; Humans
PubMed: 27411444
DOI: 10.1186/s13075-016-1069-z -
Seminars in Arthritis and Rheumatism Dec 2021Adult-onset Still's disease (AOSD) is a rare inflammatory disease, typically characterized by spiking fever, skin rash, and arthralgia or arthritis. Its conventional... (Review)
Review
BACKGROUND
Adult-onset Still's disease (AOSD) is a rare inflammatory disease, typically characterized by spiking fever, skin rash, and arthralgia or arthritis. Its conventional treatment includes NSAIDs and corticosteroids, and DMARDs as second-line therapy. Frequently, IL-1 inhibitors are also required, mainly in patients refractory to traditional therapy. Canakinumab is a monoclonal antibody that binds IL-1β with high affinity and specificity, making it appropriate for therapeutic purposes in AOSD.
OBJECTIVE
The aim of this systematic review was to identify and compile the current data on the efficacy and safety of canakinumab in the treatment of AOSD.
METHODS
Following the guidelines established by the PRISMA statement, we searched Scopus, Web of Science, Pubmed, and Cochrane Library for relevant literature up to March 2021. The inclusion criteria comprised: randomized controlled trials, pooled analyses, observational studies, case series, and case reports.
RESULTS
Seventeen studies published from 2012 to 2021 were evaluated; 11 of these correspond to case series or case reports, four observational studies, one placebo-controlled phase II trial, and one analysis of pooled systemic juvenile idiopathic arthritis data. In general, out of a total of 99 patients, 68.7% of these presented a complete remission of the systemic and arthritic manifestations at the end of the observation period, while 16.2% of the patients showed a partial improvement of the symptoms and the remaining (15.1%) did not show clinical improvement or were excluded. Moreover, 210 adverse events were reported in 69 patients during canakinumab treatment, of which the majority correspond to respiratory tract infections, arthralgia, disease flares, abdominal pain, nausea, and diarrhea, whereas the most common severe adverse events included macrophage activation syndrome and serious infections. Also, a corticosteroid-sparing effect was observed in a large percentage of patients.
CONCLUSION
More studies with solid evidence are needed to support the efficacy of canakinumab in AOSD, although its use is encouraged by the increasing favorable results reported and the efficacy of other IL-1 inhibitors. It was also associated with an acceptable safety profile, similar to expected in IL-1 inhibitor therapy. However, future studies with well-defined endpoints are warranted to examine further the usefulness of canakinumab in AOSD.
Topics: Adult; Antibodies, Monoclonal, Humanized; Arthritis, Juvenile; Humans; Macrophage Activation Syndrome; Still's Disease, Adult-Onset
PubMed: 34493394
DOI: 10.1016/j.semarthrit.2021.08.007 -
Rheumatology International Jul 2023A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and...
A literature review on new-onset autoimmune connective tissue diseases (ACTDs) following COVID-19 is lacking. We evaluated potential associations between COVID-19 and the development of new-onset ACTDs. The "population" was adults with disease terms for ACTDs, including systemic lupus erythematosus (SLE), Sjogren's syndrome, systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), anti-synthetase syndrome, mixed CTD and undifferentiated CTD, and "intervention" as COVID-19 and related terms. Databases were searched for English-language articles published until September 2022. We identified 2236 articles with 28 ultimately included. Of the 28 included patients, 64.3% were female, with a mean age was 51.1 years. The USA reported the most cases (9/28). ACTD diagnoses comprised: 11 (39.3%) IIM (including four dermatomyositis); 7 (25%) SLE; four (14.3%) anti-synthetase syndrome; four (14.3%) SSc; two (7.1%) other ACTD (one lupus/MCTD overlap). Of eight, four (14.3%) patients (including that with lupus/MCTD) had lupus nephritis. The average time from COVID-19 to ACTD diagnosis was 23.7 days. A third of patients were admitted to critical care, one for treatment of haemophagocytic lymphohistiocytosis in SLE (14 sessions of plasmapheresis, rituximab and intravenous corticosteroids) and nine due to COVID-19. 80% of patients went into remission of ACTD following treatment, while three (10%) patients died-one due to macrophage activation syndrome with anti-synthetase syndrome and two from unreported causes. Our results suggest a potential association between COVID-19 and new-onset ACTDs, notably in young females, reflecting more comprehensive CTD epidemiology. The most common diagnosis in our cohort was IIM. The aetiology and mechanisms by which ACTDs emerge following COVID-19 remain unknown and require further research.
Topics: Adult; Humans; Female; Middle Aged; Male; Mixed Connective Tissue Disease; Incidence; COVID-19; Connective Tissue Diseases; Autoimmune Diseases; Lupus Erythematosus, Systemic; Scleroderma, Systemic; Prognosis; Lupus Nephritis; Myositis
PubMed: 36786873
DOI: 10.1007/s00296-023-05283-9