The dysregulation of monocyte subpopulations in individuals at risk of developing rheumatoid arthritis

Abstract Objectives Individuals carrying antibodies against citrullinated proteins (ACPA) are at high risk of developing RA. EULAR provided a clinical definition of individuals with arthralgia suspicious for progression to RA (clinically suspect arthralgia, CSA). The alteration of monocyte subpopulations in patients with established RA has been previously described. We analysed peripheral blood monocyte subpopulations in individuals with arthralgia at risk of RA. Methods We included 70 at-risk individuals, defined as having arthralgia without arthritis and being either ACPA+ or meeting the clinical CSA definition, 23 patients with early RA (ERA) and 19 healthy controls (HCs). Monocytes classified as classical (CD14++CD16−), intermediate (CD14++CD16+/++) and nonclassical (CD14−/+CD16++) were analysed by flow cytometry. Results Of the 70 at-risk individuals, 46 were ACPA+ and 45 met the CSA definition. The at-risk individuals and, especially, ERA patients had a lower percentage of classical monocytes and a higher percentage of nonclassical monocytes than the HCs. ACPA positivity had no effect on the difference in the distribution of the monocyte subsets between at-risk individuals and ERA patients, but a difference was determined in those reaching the ERA phase. However, when compared with HCs, the shift of monocyte subsets was more significant in ACPA+ than in ACPA− individuals with arthralgia. This trend was observed in individuals who did not meet the CSA definition. This finding was, however, determined by a selection bias, as these individuals were solely ACPA+. Conclusion The shift from classical to nonclassical monocyte subpopulations was observed already in individuals at risk of developing RA.

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A Pilot Study of Circulating Monocyte Subsets in Patients Treated with Stem Cell Transplantation for High-Risk Hematological Malignancies

Medicina ◽

10.3390/medicina56010036 ◽

2020 ◽

Vol 56 (1) ◽

pp. 36 ◽

Cited By ~ 2

Author(s):

Ida Marie Rundgren ◽

Elisabeth Ersvær ◽

Aymen Bushra Ahmed ◽

Anita Ryningen ◽

Øystein Bruserud

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Peripheral Blood ◽

Hematological Malignancies ◽

Peripheral Blood Monocyte ◽

Healthy Controls ◽

Monocyte Subsets ◽

Classical Monocytes

Background and Objectives: Autologous and allogeneic stem cell transplantation is used in the treatment of high-risk hematological malignancies, and monocytes are probably involved in hematological reconstitution as well as posttransplant immunoregulation. The aim of our study was to investigate the levels of circulating monocyte subsets in allotransplant recipients. Materials and Methods: The levels of the classical, intermediate, and nonclassical monocyte subsets were determined by flow cytometry. Sixteen patients and 18 healthy controls were included, and the levels were analyzed during pretransplant remission (n = 13), early posttransplant during cytopenia (n = 9), and early reconstitution (n = 9). Results: Most patients in remission showed a majority of classical monocytes. The patients showed severe early posttransplant monocytopenia, but the total peripheral blood monocyte counts normalized very early on, and before neutrophil and platelet counts. During the first 7–10 days posttransplant (i.e., during cytopenia) a majority of the circulating monocytes showed a nonclassical phenotype, but later (i.e., 12–28 days posttransplant) the majority showed a classical phenotype. However, the variation range of classical monocytes was wider for patients in remission and during regeneration than for healthy controls. Conclusions: The total peripheral blood monocyte levels normalize at the very early stages and before neutrophil reconstitution after stem cell transplantation, and a dominance of classical monocytes is reached within 2–4 weeks posttransplant.

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CD16+Monocyte Subsets Are Increased in Large Abdominal Aortic Aneurysms and Are Differentially Related with Circulating and Cell-Associated Biochemical and Inflammatory Biomarkers

Disease Markers ◽

10.1155/2013/836849 ◽

2013 ◽

Vol 34 (2) ◽

pp. 131-142 ◽

Cited By ~ 22

Author(s):

Giorgio Ghigliotti ◽

Chiara Barisione ◽

Silvano Garibaldi ◽

Claudio Brunelli ◽

Daniela Palmieri ◽

...

Keyword(s):

Flow Cytometry ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Inflammatory Biomarkers ◽

Healthy Controls ◽

Monocyte Subsets ◽

Inflammatory Parameters ◽

Abdominal Aortic ◽

Classical Monocytes ◽

D Dimer

Proinflammatory components are present in abdominal aortic aneurysm (AAA). Circulating monocytes display heterogeneity, and three subsets have been identified, based on the differential expression for CD14 and CD16 receptors: CD14+CD16-, classical, CD14+CD16+, intermediate and CD14dimCD16+, non-classical monocytes. Increased proinflammatory CD16+monocytes with high expression of CD143 are present in CKD patients. D-dimer is increased in AAA patients, and might contribute to the pro-inflammatory response associated to circulating monocytes. We aimed to investigate the frequency of CD14+CD16+, CD14dimCD16+monocytes and monocyte CD143 expression in AAA patients, and their relationship with D-dimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14+, CD16+, CD14dimCD16+monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+SUPsets (CD14+CD16+: 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14dimCD16+: 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p<0.05). CD14+CD16+cells were associated to D-dimer and age, and to reduced eGFR. CD14dimCD16+cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16+supsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers.

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Distinct immune regulatory receptor profiles linked to altered monocyte subsets in sarcoidosis

ERJ Open Research ◽

10.1183/23120541.00804-2020 ◽

2020 ◽

pp. 00804-2020

Author(s):

Simon D. Fraser ◽

Michael G. Crooks ◽

Paul M. Kaye ◽

Simon P. Hart

Keyword(s):

Inflammatory Responses ◽

Pulmonary Sarcoidosis ◽

Receptor Expression ◽

Healthy Controls ◽

Blood Monocytes ◽

Monocyte Subsets ◽

Oral Corticosteroids ◽

Duration Of Disease ◽

Classical Monocytes ◽

Intermediate Monocytes

BackgroundIn sarcoidosis, blood monocytes, circulating precursors of granuloma macrophages, display enhanced inflammatory cytokine production, reduced expression of the regulatory (inhibitory) receptor CD200R, and altered subsets defined by CD14 and CD16. Regulatory receptors serve to dampen monocyte and macrophage inflammatory responses. We investigated the relationship between monocyte subsets and regulatory receptor expression in sarcoidosis.MethodsMulti-parameter flow cytometry was used to perform detailed analyses of cell surface regulatory molecules on freshly isolated blood immune cells from patients with chronic pulmonary sarcoidosis and age-matched healthy controls.ResultsTwenty-five patients with chronic pulmonary sarcoidosis (median duration of disease 22 months) who were not taking oral corticosteroids or other immunomodulators were recruited. Non-classical monocytes were expanded in sarcoidosis and exhibited significantly lower expression of regulatory receptors CD200R, SIRP-α, and CD47 than classical or intermediate monocytes. In sarcoidosis, all three monocyte subsets had significantly reduced CD200R and CD47 expression compared with healthy controls. A dichotomous distribution of CD200R was seen on classical and intermediate monocytes in the sarcoidosis population, with 14/25 (56%) sarcoidosis patients having a CD200R-low phenotype, and 11/25 (44%) CD200R-high. These distinct sarcoidosis monocyte phenotypes remained consistent over time.ConclusionNon-classical monocytes, which are expanded in sarcoidosis, express very low levels of regulatory receptors. Two distinct and persistent phenotypes of CD200R expression in classical and intermediate monocytes could be evaluated as sarcoidosis biomarkers.

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Abstract 13608: The Association Between Cardiometabolic Disorders/Cardiovascular Disease and the Distribution of Monocyte Subsets: A Systematic Review and Meta-Analysis

Circulation ◽

10.1161/circ.142.suppl_3.13608 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Ester Oh ◽

Muzi Na ◽

Connie Rogers

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Meta Analysis ◽

Cochrane Central Register ◽

Monocyte Subset ◽

Healthy Controls ◽

Monocyte Subsets ◽

Cardiometabolic Disorders ◽

Meta Analyses ◽

Classical Monocytes

Introduction: Monocytes play a crucial role in the pathology of atherosclerosis, a major cause of cardiovascular disease (CVD). Previous studies in preclinical models report that monocyte subsets (i.e. classical, intermediate and non-classical monocytes) may differently contribute to the pathogenesis of atherosclerosis. However, changes in the distribution and the role of each monocyte subset in cardiometabolic disorders (overweight/obesity, metabolic syndrome, hypercholesterolemia, and type 2 diabetes) and CVD in humans is less clear. Therefore, the aim of the current systematic review and meta-analysis was to evaluate the association between the monocyte subset distribution and cardiometabolic disorders/CVD in humans. Methods: Articles were systematically searched in CINAHL, Cochrane Central Register of Controlled Trials, and PubMed until April 2020. A total of 1592 articles were independently screened by 2 reviewers. A total of 25 studies were selected for qualitative analyses. Among them, 6 studies reported the percentage of each monocyte subset and were included in the meta-analyses. For the meta-analyses, a random-effects model was used to generate pooled standardized mean differences (SMD) between subjects with cardiometabolic disorders and healthy controls. Results: In total, sample size ranged from 22 to 135, and mean age of subjects ranged from 22 to 70 years. The percentage of classical monocytes was lower [SMD = -1.21; 95% CI (-1.92, -0.50); P < 0.001; I 2 = 91%] in subjects with cardiometabolic disorders compared to healthy controls. However, the percentage of intermediate [SMD = 0.56; 95% CI (0.23, 0.88); P < 0.001; I 2 = 65%] and non-classical monocytes [SMD = 1.39; 95% CI (0.59, 2.19); P < 0.001; I 2 = 93%] was higher in subjects with cardiometabolic disorders compared to healthy controls. Conclusions: There may be a shift in the distribution of monocytes from classical to intermediate and non-classical monocytes in individuals with cardiometabolic disorders. This shift may be an underlying cause of chronic low-grade inflammation, exacerbate atherosclerotic risk, and contribute to the development of CVD based on preclinical studies. However, additional mechanistic studies are needed in humans to evaluate this question.

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Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.741890 ◽

2021 ◽

Vol 8 ◽

Author(s):

Noushin Askari ◽

Christoph Lipps ◽

Sandra Voss ◽

Nora Staubach ◽

Dimitri Grün ◽

...

Keyword(s):

Myocardial Infarction ◽

Myocardial Injury ◽

Stable Coronary Artery Disease ◽

Inflammatory Cells ◽

Monocyte Subsets ◽

Coronary Syndrome ◽

Monocyte Subpopulations ◽

Artery Disease ◽

Classical Monocytes ◽

Intermediate Monocytes

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations. For this purpose, peripheral whole blood from patients with a suspected MI was used for flow cytometric measurements of the monocyte subpopulations, and myocardial injury was classified by cardiac troponin levels in serum. In patients with acute coronary syndrome (n = 82, 62.2% male) similar proportions of the monocyte subsets were associated with the two types of MI, whereas total monocyte counts were increased in patients with substantial myocardial injury vs. those with minor injury (p = 0.045). This was accompanied by a higher proportion of intermediate (p = 0.045) and classical monocytes (p = 0.059); no difference was found for non-classical monocytes (p = 0.772). In patients with chronic coronary syndrome (n = 144, 66.5% male), an independent association with myocardial injury was also observed for classical monocytes (p = 0.01) and intermediate monocytes (p = 0.08). In conclusion, changes in monocyte subpopulation counts, particularly for classical and intermediate monocytes, were related to the extent of myocardial injury in acute and stable coronary artery disease but not to the type of MI.

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Blood Monocyte Subsets and Selected Cardiovascular Risk Markers in Rheumatoid Arthritis of Short Duration in relation to Disease Activity

BioMed Research International ◽

10.1155/2014/736853 ◽

2014 ◽

Vol 2014 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Ewa Klimek ◽

Tomasz Mikołajczyk ◽

Joanna Sulicka ◽

Beata Kwaśny-Krochin ◽

Mariusz Korkosz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Short Duration ◽

Subclinical Atherosclerosis ◽

Intima Media Thickness ◽

Peripheral Blood Monocyte ◽

Blood Monocyte ◽

Monocyte Subsets ◽

Hla Dr ◽

Monocyte Subpopulations

Objectives. To evaluate blood monocyte subsets and functional monocyte properties in patients with rheumatoid arthritis (RA) of short duration in the context of cardiovascular (CV) risk and disease activity.Methods. We studied conventional markers of CV risk, intima media thickness (IMT), and blood monocyte subsets in 27 patients aged 41 ± 10 years with RA of short duration (median 12 months) and 22 healthy controls. The RA subjects were divided into low (DAS28: 2.6–5.1) and high (DAS28 > 5.1) disease activity.Results. RA patients exhibited increased levels of intermediate (CD14++CD16+) monocytes with decreased CD45RA expression compared to controls, increased counts of classical (CD14++CD16−) monocytes, and decreased percentages of nonclassical (CD14+CD16++) monocytes. Patients with high disease activity had lower HLA DR expression on classical monocytes compared to low disease activity patients. There were no differences in monocyte subsets between subjects with DAS > 5.1 and DAS ≤ 5.1. There were no significant intergroup differences in IMT and the majority of classical CV risk factors.Conclusions. Patients with RA of short duration show alteration in peripheral blood monocyte subsets despite the fact that there is no evidence of subclinical atherosclerosis. Disease activity assessed with DAS28 was associated with impaired functional properties but not with a shift in monocyte subpopulations.

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The Distinction between [P] and [S]

10.23943/princeton/9780691161006.003.0018 ◽

2017 ◽

Author(s):

Galen Strawson

Keyword(s):

Personal Identity ◽

Radical Change ◽

Legal Responsibility ◽

The Difference ◽

Definition Of ◽

Over Time

This chapter examines the difference between John Locke's definition of a person [P], considered as a kind of thing, and his definition of a subject of experience of a certain sophisticated sort [S]. It first discusses the equation [P] = [S], where [S] is assumed to be a continuing thing that is able to survive radical change of substantial realization, as well as Locke's position about consciousness in relation to [P]'s identity or existence over time as [S]. It argues that Locke is not guilty of circularity because he is not proposing consciousness as the determinant of [S]'s identity over time, but only of [S]'s moral and legal responsibility over time. Finally, it suggests that the terms “Person” and “Personal identity” pull apart, in Locke's scheme of things, but in a perfectly coherent way.

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L'anglicisme dans la langue française

Digital Press Social Sciences and Humanities ◽

10.29037/digitalpress.43286 ◽

2019 ◽

Vol 3 ◽

pp. 00013

Author(s):

Danny Susanto

Keyword(s):

English Language ◽

Oil Industry ◽

English Word ◽

Public Institutions ◽

Font Size ◽

The World ◽

French Speaking ◽

The Difference ◽

Definition Of ◽

Bibliographic Study

The purpose of this study is to analyze the phenomenon known as “anglicism”: a loan made to the English language by another language. Anglicism arose either from the adoption of an English word as a result of a translation defect despite the existence of an equivalent term in the language of the speaker, or from a wrong translation, as a word-by-word translation. Said phenomenon is very common nowadays and most languages of the world including making use of some linguistic concepts such as anglicism, neologism, syntax, morphology etc, this article addresses various aspects related to Anglicisms in French through a bibliographic study: the definition of Anglicism, the origin of Anglicisms in French and the current situation, the areas most affected by Anglicism, the different categories of Anglicism, the difference between French Anglicism in France and French-speaking Canada, the attitude of French-speaking society towards to the Anglicisms and their efforts to stop this phenomenon. The study shows that the areas affected are, among others, trade, travel, parliamentary and judicial institutions, sports, rail, industrial production and most recently film, industrial production, sport, oil industry, information technology, science and technology. Various initiatives have been implemented either by public institutions or by individuals who share concerns about the increasingly felt threat of the omnipresence of Anglicism in everyday life.

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Definitions and Concepts for Quantitative Rockfall Hazard and Risk Analysis

Geosciences ◽

10.3390/geosciences11040158 ◽

2021 ◽

Vol 11 (4) ◽

pp. 158

Author(s):

Didier Hantz ◽

Jordi Corominas ◽

Giovanni B. Crosta ◽

Michel Jaboyedoff

Keyword(s):

Risk Assessment ◽

At Risk ◽

Failure Probability ◽

Rockfall Hazard ◽

Process Failure ◽

Failure Propagation ◽

Element At Risk ◽

Hazard And Risk ◽

Hazard And Risk Assessment ◽

Definition Of

There is an increasing need for quantitative rockfall hazard and risk assessment that requires a precise definition of the terms and concepts used for this particular type of landslide. This paper suggests using terms that appear to be the most logic and explicit as possible and describes methods to derive some of the main hazards and risk descriptors. The terms and concepts presented concern the rockfall process (failure, propagation, fragmentation, modelling) and the hazard and risk descriptors, distinguishing the cases of localized and diffuse hazards. For a localized hazard, the failure probability of the considered rock compartment in a given period of time has to be assessed, and the probability for a given element at risk to be impacted with a given energy must be derived combining the failure probability, the reach probability, and the exposure of the element. For a diffuse hazard that is characterized by a failure frequency, the number of rockfalls reaching the element at risk per unit of time and with a given energy (passage frequency) can be derived. This frequency is relevant for risk assessment when the element at risk can be damaged several times. If it is not replaced, the probability that it is impacted by at least one rockfall is more relevant.

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Ability of radiofrequency echographic multispectrometry to identify osteoporosis status in elderly women with type 2 diabetes

Aging Clinical and Experimental Research ◽

10.1007/s40520-021-01889-w ◽

2021 ◽

Author(s):

Carla Caffarelli ◽

Maria Dea Tomai Pitinca ◽

Antonella Al Refaie ◽

Elena Ceccarelli ◽

Stefano Gonnelli

Keyword(s):

Type 2 Diabetes ◽

Lumbar Spine ◽

Elderly Women ◽

Fragility Fractures ◽

Dual Energy ◽

Healthy Controls ◽

Diagnosis Of Osteoporosis ◽

X Ray ◽

The Difference

Abstract Background Patients with type 2 diabetes (T2DM) have an increased or normal BMD; however fragility fractures represent one of the most important complications of T2DM. Aims This study aimed to evaluate whether the use of the Radiofrequency Echographic multi spectrometry (REMS) technique may improve the identification of osteoporosis in T2DM patients. Methods In a cohort of 90 consecutive postmenopausal elderly (70.5 ± 7.6 years) women with T2DM and in 90 healthy controls we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD) and total hip (TH-BMD) using a dual-energy X-ray absorptiometry device; moreover, REMS scans were also carried out at the same axial sites. Results DXA measurements were all higher in T2DM than in non-T2DM women; instead, all REMS measurements were lower in T2DM than in non T2DM women. Moreover, the percentage of T2DM women classified as “osteoporotic”, on the basis of BMD by REMS was markedly higher with respect to those classified by DXA (47.0% vs 28.0%, respectively). On the contrary, the percentage of T2DM women classified as osteopenic or normal by DXA was higher with respect to that by REMS (48.8% and 23.2% vs 38.6% and 14.5%, respectively). T2DM women with fragility fractures presented lower values of both BMD-LS by DXA and BMD-LS by REMS with respect to those without fractures; however, the difference was significant only for BMD-LS by REMS (p < 0.05). Conclusions Our data suggest that REMS technology may represent a useful approach to enhance the diagnosis of osteoporosis in patients with T2DM.

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