-
Frontiers in Immunology 2023Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several... (Review)
Review
Glutamate, as one of the most important carbon sources in the TCA cycle, is central in metabolic processes that will subsequently influence tumor progression. Several factors can affect the expression of glutamate receptors, playing either a tumor-promoting or tumor-suppressor role in cancer. Thus, the activation of glutamate receptors by the ligand could play a role in tumor development as ample studies have demonstrated the expression of glutamate receptors in a broad range of tumor cells. Glutamate and its receptors are involved in the regulation of different immune cells' development and function, as suggested by the receptor expression in immune cells. The activation of glutamate receptors can enhance the effectiveness of the effector's T cells, or decrease the cytokine production in immunosuppressive myeloid-derived suppressor cells, increasing the antitumor immune response. These receptors are essential for the interaction between tumor and immune cells within the tumor microenvironment (TME) and the regulation of antitumor immune responses. Although the role of glutamate in the TCA cycle has been well studied, few studies have deeply investigated the role of glutamate receptors in the regulation of cancer and immune cells within the TME. Here, by a systematic review of the available data, we will critically assess the physiopathological relevance of glutamate receptors in the regulation of cancer and immune cells in the TME and provide some unifying hypotheses for futures research on the role of glutamate receptors in the immune modulation of the tumor.
Topics: Humans; Tumor Microenvironment; Neoplasms; T-Lymphocytes; Glutamic Acid; Receptors, Glutamate
PubMed: 36817470
DOI: 10.3389/fimmu.2023.1123841 -
Current Opinion in Rheumatology Jan 2023Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent...
PURPOSE OF THE REVIEW
Emerging data suggest that regulatory T-cells (Treg) alterations play a major role in systemic vasculitis pathophysiology. We performed a systematic review of recent advances in the role of Treg and interleukin (IL)-10 in the pathogenesis and treatment of systemic vasculitis, including giant cell arteritis (GCA), Takayasu arteritis, Behçet's disease, antineutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV), and cryoglobulinemia associated vasculitis.
RECENT FINDINGS
Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Decreased peripheral blood frequencies of Treg are described in all vasculitis when compared to healthy donors. Altered Treg functions are reported in GCA, Takayasu arteritis, AAV, and Behçet's disease with different mechanisms proposed. Treatment with biologics, and sometimes other immunosuppressants, may restore Treg frequencies and/or immune activity with significant differences in active disease or disease in remission in several systemic vasculitis. IL-10 is elevated in GCA, AAV, cryoglobulinemia associated vasculitis. In Behçet's disease, IL-10 is decreased in peripheral blood and elevated in saliva. In Takayasu arteritis, IL-10 levels were essentially elevated in patients' vessel wall. Several new therapeutic approaches targeting Treg and Il-10 (low dose IL-2, CAR Treg…) are developed to treat patients with systemic vasculitis.
SUMMARY
Treg and IL-10 play a central role in the regulation of inflammation in vasculitis and new targeting approaches are emerging.
Topics: Humans; T-Lymphocytes, Regulatory; Interleukin-10; Behcet Syndrome; Giant Cell Arteritis; Takayasu Arteritis; Systemic Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
PubMed: 36508306
DOI: 10.1097/BOR.0000000000000915 -
Acta Neurologica Scandinavica Jun 2021Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which causes demyelination and neuroaxonal damage. Low-grade systemic...
Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, which causes demyelination and neuroaxonal damage. Low-grade systemic inflammation has been suggested to contribute to the pathogenesis due to amplification of pathogenic immune activation. However, there is a lack of reliable biomarkers of systemic inflammation predicting disease activity and progression in MS. The neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) have been identified as biomarkers of severity and disease activity in various disorders. In September 2020, we conducted a systematic literature search on multiple databases on studies reporting NLR values or CRP levels in MS. The aim of this systematic review was to highlight the current knowledge about the potential of NLR and CRP as biomarkers in MS. A total of nineteen articles qualified for inclusion. Data on CRP were included in fourteen studies and NLR in nine studies. The results regarding CRP were inconsistent, and present literature does not support the use of CRP as a diagnostic or prognostic biomarker in MS. In contrast, NLR values were increased in MS patients compared with healthy controls in all case-control studies. Furthermore, NLR was associated with disease activity in untreated patients. Our systematic review therefore indicates that NLR might serve as a potential biomarker of disease activity. Given that the results of NLR are mainly drawn from retrospective case-control or cross-sectional studies, future prospective studies with long-term follow-up are required to accurately determine optimal timing and cutoff values that may be used in the clinical setting.
Topics: Biomarkers; C-Reactive Protein; Female; Humans; Inflammation; Lymphocyte Count; Male; Middle Aged; Multiple Sclerosis; Neutrophils; Prospective Studies
PubMed: 33591593
DOI: 10.1111/ane.13401 -
Vector Borne and Zoonotic Diseases... Jul 2016In high-income countries, homeless individuals in urban areas often live in crowded conditions with limited sanitation and personal hygiene. The environment of... (Review)
Review
INTRODUCTION
In high-income countries, homeless individuals in urban areas often live in crowded conditions with limited sanitation and personal hygiene. The environment of homelessness in high-income countries may result in intensified exposure to ectoparasites and urban wildlife, which can transmit infections. To date, there have been no systematic evaluations of the published literature to assess vector-borne and zoonotic disease risk to these populations.
OBJECTIVES
The primary objectives of this study were to identify diversity, prevalence, and risk factors for vector-borne and zoonotic infections among people experiencing homelessness and extreme poverty in urban areas of high-income countries.
METHODS
We conducted a systematic review and narrative synthesis of published epidemiologic studies of zoonotic and vector-borne infections among urban homeless and very poor people in the United States and Europe from 1990 to 2014.
RESULTS
Thirty-one observational studies and 14 case studies were identified (n = 45). Seroprevalence to the human louse-borne pathogen Bartonella quintana (seroprevalence range: 0-37.5%) was identified most frequently, with clinical disease specifically observed among HIV-positive individuals. Seropositivity to Bartonella henselae (range: 0-10.3%) and Rickettsia akari (range: 0-16.2%) was noted in multiple studies. Serological evidence of exposure to Rickettsia typhi, Rickettsia prowazekii, Bartonella elizabethae, West Nile virus, Borellia recurrentis, lymphocytic choriomeningitis virus, Wohlfartiimonas chitiniclastica, Seoul hantavirus (SEOV), and Leptospira species was also identified in published studies, with SEOV associated with chronic renal disease later in life. HIV infection, injection drug use, and heavy drinking were noted across multiple studies as risk factors for infection with vector-borne and zoonotic pathogens.
CONCLUSIONS
B. quintana was the most frequently reported vector-borne infection identified in our article. Delousing efforts and active surveillance among HIV-positive individuals, who are at elevated risk of complication from B. quintana infection, are advised to reduce morbidity. Given documented exposure to rodent-borne zoonoses among urban homeless and marginalized people, reducing human contact with rodents remains an important public health priority.
Topics: Animals; Bacterial Infections; Europe; Ill-Housed Persons; Humans; Social Marginalization; United States; Zoonoses
PubMed: 27159039
DOI: 10.1089/vbz.2015.1863 -
Rheumatology and Therapy Aug 2022Belimumab is a recombinant human monoclonal antibody that binds to soluble B-lymphocyte stimulator and inhibits its biological activity. Since receiving approvals for... (Review)
Review
INTRODUCTION
Belimumab is a recombinant human monoclonal antibody that binds to soluble B-lymphocyte stimulator and inhibits its biological activity. Since receiving approvals for the treatment of systemic lupus erythematosus (SLE), several observational studies have investigated the effectiveness of belimumab in the real-world setting. This study reports a systematic review and meta-analysis of the literature to evaluate the real-world effectiveness of belimumab for the treatment of SLE.
METHODS
A literature search following PRISMA Guidelines and limited to studies in English was performed (2014-2020) to identify relevant studies reporting effectiveness outcomes of belimumab in patients with SLE. A modified version of the Newcastle-Ottawa Scale was used to assess study quality. Outcomes, including SLE Disease Activity Index (SLEDAI) score, prednisone-equivalent use, and SLE flare were pooled and analyzed using statistical aggregation methods.
RESULTS
The literature search identified 514 articles for initial review. Of these, 17 articles were suitable for data extraction and summary. Baseline characteristics of patients in real-world studies were generally similar to those of relevant clinical trials, including age, sex, disease duration, SLEDAI score, and prednisone-equivalent use. Real-world use of belimumab was associated with reductions in SLEDAI score (mean baseline score to month 6: 10.1-4.4; 57% reduction), prednisone-equivalent dosing (mean baseline dose to month 6: 12.1 mg/day to 6.9 mg/day; 43% reduction), and flare frequency (12 months prior to belimumab to 12 months after belimumab: 1.15-0.39 mean flares per patient per year; 66% reduction). Long-term data (up to 2 years post-treatment initiation) for SLEDAI score and prednisone-equivalent dose indicated that improvements in both outcomes continue over time among patients remaining on therapy.
CONCLUSIONS
In the real-world setting, observed outcomes with belimumab for the treatment of SLE are consistent with those reported from randomized clinical trials. Improvements persist long-term for SLEDAI activity and prednisone-equivalent use with belimumab.
PubMed: 35596922
DOI: 10.1007/s40744-022-00454-9 -
International Journal of Molecular... Nov 2022Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade... (Meta-Analysis)
Meta-Analysis Review
Activation of the Monocyte/Macrophage System and Abnormal Blood Levels of Lymphocyte Subpopulations in Individuals with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.
Autism spectrum disorder (ASD) is a neurodevelopmental condition with a so far unknown etiology. Increasing evidence suggests that a state of systemic low-grade inflammation may be involved in the pathophysiology of this condition. However, studies investigating peripheral blood levels of immune cells, and/or of immune cell activation markers such as neopterin are lacking and have provided mixed findings. We performed a systematic review and meta-analysis of studies comparing total and differential white blood cell (WBC) counts, blood levels of lymphocyte subpopulations and of neopterin between individuals with ASD and typically developing (TD) controls (PROSPERO registration number: CRD CRD42019146472). Online searches covered publications from 1 January 1994 until 1 March 2022. Out of 1170 publication records identified, 25 studies were finally included. Random-effects meta-analyses were carried out, and sensitivity analyses were performed to control for potential moderators. Results: Individuals with ASD showed a significantly higher WBC count (k = 10, g = 0.29, p = 0.001, I2 = 34%), significantly higher levels of neutrophils (k = 6, g = 0.29, p = 0.005, I2 = 31%), monocytes (k = 11, g = 0.35, p < 0.001, I2 = 54%), NK cells (k = 7, g = 0.36, p = 0.037, I2 = 67%), Tc cells (k = 4, g = 0.73, p = 0.021, I2 = 82%), and a significantly lower Th/Tc cells ratio (k = 3, g = −0.42, p = 0.008, I2 = 0%), compared to TD controls. Subjects with ASD were also characterized by a significantly higher neutrophil-to-lymphocyte ratio (NLR) (k = 4, g = 0.69, p = 0.040, I2 = 90%), and significantly higher neopterin levels (k = 3, g = 1.16, p = 0.001, I2 = 97%) compared to TD controls. No significant differences were found with respect to the levels of lymphocytes, B cells, Th cells, Treg cells, and Th17 cells. Sensitivity analysis suggested that the findings for monocyte and neutrophil levels were robust, and independent of other factors, such as medication status, diagnostic criteria applied, and/or the difference in age or sex between subjects with ASD and TD controls. Taken together, our findings suggest the existence of a chronically (and systemically) activated inflammatory response system in, at least, a subgroup of individuals with ASD. This might have not only diagnostic, but also, therapeutic implications. However, larger longitudinal studies including more homogeneous samples and laboratory assessment methods and recording potential confounding factors such as body mass index, or the presence of comorbid psychiatric and/or medical conditions are urgently needed to confirm the findings.
Topics: Humans; Monocytes; Autism Spectrum Disorder; Neopterin; Leukocytes; Lymphocyte Subsets; Th17 Cells; Macrophages
PubMed: 36430805
DOI: 10.3390/ijms232214329 -
International Journal of Environmental... Apr 2023The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group... (Meta-Analysis)
Meta-Analysis Review
The rate of new human immunodeficiency virus (HIV) infections globally is alarming. Although antiretroviral therapy (ART) improves the quality of life among this group of patients, ARTs are associated with risk of cardiovascular diseases (CVD). Moreover, virally suppressed patients still experience immune activation associated with HIV migration from reservoir sites. Statins are widely recommended as therapeutic agents to control ART-related CVD; however, their impacts on the cluster of differentiation (CD)4 count and viral load are inconsistent. To assess the effect of statins on markers of HIV infections, immune activation and cholesterol, we thoroughly reviewed evidence from randomised controlled trials. We found 20 relevant trials from three databases with 1802 people living with HIV (PLHIV) on statin-placebo treatment. Our evidence showed no significant effect on CD4 T-cell count standardised mean difference (SMD): (-0.59, 95% confidence intervals (CI): (-1.38, 0.19), = 0.14) following statin intervention in PLHIV on ART. We also found no significant difference in baseline CD4 T-cell count (SD: (-0.01, 95%CI: (-0.25, 0.23), = 0.95). Our findings revealed no significant association between statins and risk of viral rebound in PLHIV with undetectable viral load risk ratio (RR): (1.01, 95% CI: (0.98, 1.04), = 0.65). Additionally, we found a significant increase in CD8CD38HLA-DR T-cells (SMD (1.10, 95% CI: (0.93, 1.28), < 0.00001) and CD4CD38HLA-DR T-cells (SMD (0.92, 95% CI: (0.32, 1.52), = 0.003). Finally, compared to placebo, statins significantly reduced total cholesterol (SMD: (-2.87, 95% CI: (-4.08, -1.65), < 0.0001)). Our results suggest that the statin lipid-lowering effect in PLHIV on ART may elevate immune activation without influencing the viral load and CD4 count. However, due to the limited evidence synthesised in this meta-analysis, we recommend that future powered trials with sufficient sample sizes evaluate statins' effect on CD4 count and viral load, especially in virally suppressed patients.
Topics: Humans; HIV Infections; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Quality of Life; HIV-1; HLA-DR Antigens; CD4 Lymphocyte Count; Cardiovascular Diseases; Cholesterol; Viral Load
PubMed: 37174188
DOI: 10.3390/ijerph20095668 -
Health Science Reports May 2022Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to... (Review)
Review
BACKGROUND AND AIMS
Older people have higher rates of comorbidities and may experience more severe inflammatory responses; therefore, are at higher risk of death. Herein, we aimed to systematically review the mortality in coronavirus disease 2019 (COVID-19) patients and its predictors in this age group.
METHODS
We searched PubMed, Web of Science, and Science Direct using relevant keywords. Retrieved records underwent a two-step screening process consisting of title/abstract and full-text screenings to identify the eligible studies.
RESULTS
Summarizing findings of 35 studies demonstrated that older patients have higher mortality rates compared to the younger population. A review of articles revealed that increasing age, body mass index, a male gender, dementia, impairment or dependency in daily activities, presence of consolidations on chest X-ray, hypoxemic respiratory failure, and lower oxygen saturation at admission were risk factors for death. High d-dimer levels, 25-hydroxy vitamin D serum deficiencies, high C-reactive protein (≥5 mg/L) levels plus any other abnormalities of lymphocyte, higher blood urea nitrogen or lactate dehydrogenase, and higher platelet count were predictors of poor prognosis and mortality in the elderly. Studies have also shown that previous treatment with renin-angiotensin-aldosterone system inhibitors, pharmacological treatments of respiratory disorders, antibiotics, corticosteroids, vitamin K antagonist, antihistamines, azithromycin, Itolizumab (an anti-CD6 monoclonal antibody) in combination with other antivirals reduces COVID-19 worsening and mortality. Vaccination against seasonal influenza might also reduce COVID-19 mortality.
CONCLUSION
Overall, a critical consideration is necessary for the care and management of COVID-19 in the aged population considering the drastic contrasts in manifestation and prognosis compared to other age groups. Mortality from COVID-19 is independently associated with the patient's age. Elderly patients with COVID-19 are more vulnerable to poor outcomes. Thus, strict preventive measures, timely diagnosis, and aggressive therapeutic/nontherapeutic care are of great importance to reduce acute respiratory distress syndrome and severe complications in older people.
PubMed: 35620541
DOI: 10.1002/hsr2.657 -
Arthritis Research & Therapy Oct 2017The aim of this study was to identify the most reliable biomarkers in the literature that could be used as flare predictors in systemic lupus erythematosus (SLE). (Review)
Review
BACKGROUND
The aim of this study was to identify the most reliable biomarkers in the literature that could be used as flare predictors in systemic lupus erythematosus (SLE).
METHODS
A systematic review of the literature was performed using two databases (MEDLINE and EMBASE) through April 2015 and congress abstracts from the American College of Rheumatology and the European League Against Rheumatism were reviewed from 2010 to 2014. Two independent reviewers screened titles and abstracts and analysed selected papers in detail, using a specific questionnaire. Reports addressing the relationships between one or more defined biological test(s) and the occurrence of disease exacerbation were included in the systematic review.
RESULTS
From all of the databases, 4668 records were retrieved, of which 69 studies or congress abstracts were selected for the systematic review. The performance of seven types of biomarkers performed routinely in clinical practice and nine types of novel biological markers was evaluated. Despite some encouraging results for anti-double-stranded DNA antibodies, anti-C1q antibodies, B-lymphocyte stimulator and tumour necrosis factor-like weak inducer of apoptosis, none of the biomarkers stood out from the others as a potential gold standard for flare prediction. The results were heterogeneous, and a lack of standardized data prevented us from identifying a powerful biomarker.
CONCLUSIONS
No powerful conclusions could be drawn from this systematic review due to a lack of standardized data. Efforts should be undertaken to optimize future research on potential SLE biomarkers to develop validated candidates. Thus, we propose a standardized pattern for future studies.
Topics: Antibodies, Antinuclear; B-Cell Activating Factor; Biomarkers; C-Reactive Protein; Complement C1q; Cytokine TWEAK; Humans; Lupus Erythematosus, Systemic; Prognosis; Sensitivity and Specificity
PubMed: 29065901
DOI: 10.1186/s13075-017-1442-6 -
The Journal of Investigative Dermatology Nov 2022Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to... (Meta-Analysis)
Meta-Analysis
Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
Topics: Rats; Animals; Burns; Neutrophils; Macrophages; Anti-Bacterial Agents; Inflammation Mediators
PubMed: 35623415
DOI: 10.1016/j.jid.2022.05.004