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Frontiers in Medicine 2021Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not...
Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not considered as a frequent complication of pSLE; however, its occurrence could be under-estimated and the diagnosis can be challenging. In order to address this issue, we performed a systematic review of the available medical literature, aiming to retrieve all those papers providing diagnostic (clinical/laboratory) data on patients with pSLE-related MAS, in individual or aggregated form. The selected case reports and series provided a pool of 46 patients, accounting for 48 episodes of MAS in total. We re-analyzed these patients in light of the diagnostic criteria for MAS validated in systemic Juvenile Idiopathic Arthritis (sJIA) patients and the preliminary diagnostic criteria for MAS in pSLE, respectively. Five clinical studies were also selected and used to support this analysis. This systematic review confirms that MAS diagnosis in pSLE patients is characterized by several diagnostic challenges, which could lead to delayed diagnosis and/or under-estimation of this complication. Specific criteria should be considered to diagnose MAS in different rheumatic diseases; as regards pSLE, the aforementioned preliminary criteria for MAS in pSLE seem to perform better than the sJIA-related MAS criteria, because of a lower ferritin cut-off.
PubMed: 34150813
DOI: 10.3389/fmed.2021.681875 -
AIDS (London, England) Sep 2022Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the...
OBJECTIVE
Both obesity and HIV infection are characterized by a state of chronic inflammation associated with increased morbidity and mortality. This review aims to assess the available literature on immune dysregulation in obesity and people with HIV infection (PWH).
DESIGN
A systematic review of peer-reviewed literature.
METHODS
We conducted a systematic literature search of PubMed, Embase, Scopus, and international conference abstracts for articles on the epidemiology of obesity in the general population and in PWH and the pathogenesis of obesity with a focus on inflammation and immune activation.
RESULTS
Of the 631 articles selected after title review, 490 met the inclusion criteria and 90 were included in the final selection. The selected studies highlight the increasing prevalence of obesity in PWH and a substantial role for antiretroviral treatment (ART) in its development. Pathogenesis of obesity and its associated inflammation derives from disturbances in adipose tissue (AT) immune function, focused on T-cell and macrophage function, with a switch to pro-inflammatory immune phenotype and resulting increases in pro-inflammatory chemokines, which contribute to the development of metabolic syndrome. Although dysregulation of these pathways is seen in both obesity and HIV, there remains a lack of human studies on AT inflammation in HIV.
CONCLUSION
Obesity is an emerging comorbidity in PWH, with a substantial overlap in immune dysregulation patterns seen in both conditions. How this immune dysfunction impacts on development of metabolic complications for both obesity and HIV infection, and whether targeting of AT-derived inflammation will improve outcomes in PWH requires further study.
Topics: Anti-Retroviral Agents; HIV Infections; Host-Pathogen Interactions; Humans; Inflammation; Obesity
PubMed: 35979828
DOI: 10.1097/QAD.0000000000003281 -
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 -
Fundamental & Clinical Pharmacology Apr 2023Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of... (Meta-Analysis)
Meta-Analysis Review
Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.
Topics: Humans; Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Anti-Inflammatory Agents; Macrophages; Mice, Inbred C57BL; Peptide Fragments
PubMed: 36300567
DOI: 10.1111/fcp.12844 -
PloS One Jan 2011Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Natural resistance associated macrophage protein 1 (NRAMP1), encoded by the SLC11A1 gene, has been described to regulate macrophage activation and be associated with infectious and autoimmune diseases. The relation between SLC11A1 polymorphisms and tuberculosis susceptibility has been studied in different populations.
METHODS
We systematically reviewed published studies on SLC11A1 polymorphisms and tuberculosis susceptibility until September 15, 2010 and quantitatively summarized associations of the most widely studied polymorphisms using meta-analysis.
RESULTS
In total, 36 eligible articles were included in this review. In Meta-analysis, significant associations were observed between tuberculosis risk and widely studied SLC11A1 polymorphisms with summarized odds ratio of 1.35 (95%CI, 1.17-1.54), 1.25 (95% CI, 1.04-1.50), 1.23 (95% CI, 1.04-1.44), 1.31 (95%CI, 1.08-1.59) for 3' UTR, D543N, INT4, and 5' (GT)n, respectively. Heterogeneity between studies was not pronounced, and the associations did not remarkably vary in the stratified analysis with respect to study population and study base.
CONCLUSIONS
The association between SLC11A1 polymorphisms and tuberculosis susceptibility observed in our analyses supports the hypothesis that NRAMP1 might play an important role in the host defense to the development of tuberculosis.
Topics: Cation Transport Proteins; Genetic Predisposition to Disease; Humans; Polymorphism, Genetic; Tuberculosis
PubMed: 21283567
DOI: 10.1371/journal.pone.0015831 -
Materials (Basel, Switzerland) Oct 2022Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to... (Review)
Review
UNLABELLED
Immunomodulatory biomaterials have the potential to stimulate an immune response able to promote constructive and functional tissue remodeling responses as opposed to persistent inflammation and scar tissue formation. As such, the controlled activation of macrophages and modulation of their phenotype through implant surface modification has emerged as a key therapeutic strategy.
METHODS
Online databases were searched for in vitro studies between January 1991 and June 2020 which examined the effect of titanium implant surface topography on the adherent macrophage phenotype at either the gene or protein level.
RESULTS
Thirty-nine studies were subsequently included for review. Although there was significant heterogeneity between studies, treatment of titanium surfaces increased the surface roughness or hydrophilicity, and hence increased macrophage attachment but decreased cell spreading. Physical coating of the titanium surface also tended to promote the formation of cell clusters. Titanium and titanium-zirconium alloy with a micro- or nano-scale rough topography combined with a hydrophilic surface chemistry were the most effective surfaces for inducing an anti-inflammatory phenotype in adherent macrophages, as indicated by significant changes in cytokine gene expression and or cytokine secretion profiles.
CONCLUSIONS
The published data support the hypothesis that incorporation of specific topographical and physiochemical surface modifications to titanium can modulate the phenotypic response of adherent macrophages.
PubMed: 36295379
DOI: 10.3390/ma15207314 -
Pediatric Blood & Cancer Mar 2023Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Risk factors of mortality in critically ill children with hemophagocytic lymphohistiocytosis (HLH) are not well described. This systematic review aims to determine overall mortality of critically ill children with HLH, and describes etiologies, treatment, and pediatric intensive care unit (PICU) support employed.
DATA SOURCES
PubMed, Embase, Web of Science, CINAHL, and Cochrane Library from inception until February 28, 2022.
STUDY SELECTION
Observational studies and randomized controlled trials reporting children aged 18 years or below, diagnosed with HLH and admitted to the PICU.
DATA EXTRACTION
Etiologies, treatment modalities, PICU therapies, and mortality outcomes were summarized. Random-effects meta-analysis was performed.
DATA SYNTHESIS
Total 36 studies (total patients = 493, mean age: 49.5 months [95% confidence interval (CI): 30.9-79.5]) were included. Pooled mortality rate was 32.6% (95% CI: 23.4-42.4). The most frequent etiologies for HLH were infections (53.3%) and primary HLH (12.8%), while the remaining cases were due to other causes of secondary HLH, including autoimmune diseases, malignancy, and drug-induced and idiopathic HLH. Pooled mortality rate was higher in primary than secondary HLH (72.2%, 95% CI: 57.8-84.5 vs. 23.9%, 95% CI: 14.4-35.02; p < .01). Univariate analysis found that treatment with etoposide was associated with higher mortality, while intravenous immunoglobulins (IVIGs) were associated with lower mortality. Conversely, multivariable analysis adjusted for etiology demonstrated no association between etoposide and IVIG use, and mortality. Twenty-one studies (total patients = 278) had detailed information on PICU therapies. Mechanical ventilation (MV), continuous renal replacement therapy, and inotropes were used in 107 (38.5%), 66 (23.7%), and 51 patients (18.3%), respectively. Need for MV was associated with increased risk of mortality (mean difference = 28%, 95% CI: 9-47).
CONCLUSION
Critically ill children with HLH have high mortality rates and require substantial PICU support. Collaborative work between multiple centers with standardized data collection can potentially provide more robust data.
Topics: Humans; Child; Child, Preschool; Lymphohistiocytosis, Hemophagocytic; Etoposide; Critical Illness; Retrospective Studies; Intensive Care Units, Pediatric; Immunoglobulins, Intravenous
PubMed: 36579732
DOI: 10.1002/pbc.30122 -
Current Opinion in Allergy and Clinical... Oct 2015A large number of studies investigating the correlation between severity of atopic dermatitis and various biomarkers have been published over the past decades. The aim... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
A large number of studies investigating the correlation between severity of atopic dermatitis and various biomarkers have been published over the past decades. The aim of this review was to identify, evaluate and synthesize the evidence examining the correlation of biomarkers with disease severity in atopic dermatitis patients, something that has not been performed previously.
RECENT FINDINGS
Three electronic databases were systematically searched and relevant studies were selected for inclusion. A total of 222 articles, reporting on 115 different biomarkers in 30 063 patients, were critically appraised. Studies were divided into two main groups. The first group consisted of longitudinal randomized controlled trials and cohort studies, which reported measurements at multiple time points. The second contained cross-sectional studies that reported only one measurement per patient. Out of 222 articles, 108 articles reported sufficient data for meta-analysis. Only four biomarkers were eligible for meta-analysis in the longitudinal group, and nine in the cross-sectional group.
SUMMARY
Serum thymus and activation-regulated chemokine (TARC) was found to be the most reliable biomarker studied, showing pooled correlation coefficients of 0.60 (95% CI 0.48-0.70) and 0.64 (95% CI 0.57-0.70) in longitudinal and cross-sectional studies, respectively. Additional biomarkers that could prove useful but require additional research include serum cutaneous T-cell attracting chemokine (CTACK), sE-selectin, macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH) and interleukin (IL)-18.
Topics: Biomarkers; Chemokine CCL17; Chemokine CCL22; Chemokine CCL27; Dermatitis, Atopic; E-Selectin; Humans; Interleukin-18; L-Lactate Dehydrogenase
PubMed: 26226355
DOI: 10.1097/ACI.0000000000000198 -
Journal of Leukocyte Biology Mar 2023Despite effective antiretroviral therapies, chronic inflammation and spontaneous viral "blips" occur in HIV-infected patients. Given the roles for monocytes/macrophages...
Despite effective antiretroviral therapies, chronic inflammation and spontaneous viral "blips" occur in HIV-infected patients. Given the roles for monocytes/macrophages in HIV pathogenesis and extracellular vesicles in intercellular communication, we performed this systematic review to delineate the triad of HIV, monocytes/macrophages, and extracellular vesicles in the modulation of immune activation and HIV activities. We searched PubMed, Web of Science, and EBSCO databases for published articles, up to 18 August 2022, relevant to this triad. The search identified 11,836 publications, and 36 studies were deemed eligible and included in this systematic review. Data were extracted for the characteristics of HIV, monocytes/macrophages, and extracellular vesicles used for experiments and the immunologic and virologic outcomes in extracellular vesicle recipient cells. Evidence for the effects on outcomes was synthesized by stratifying the characteristics by outcomes. In this triad, monocytes/macrophages were potential producers and recipients of extracellular vesicles, whose cargo repertoires and functionalities were regulated by HIV infection and cellular stimulation. Extracellular vesicles derived from HIV-infected monocytes/macrophages or the biofluid of HIV-infected patients enhanced innate immune activation and HIV dissemination, cellular entry, replication, and latency reactivation in bystander or infected target cells. These extracellular vesicles could be synthesized in the presence of antiretroviral agents and elicit pathogenic effects in a wide range of nontarget cells. At least eight functional types of extracellular vesicles could be classified based on the diverse extracellular vesicle effects, which were linked to specific virus- and/or host-derived cargos. Thus, the monocyte/macrophage-centered multidirectional crosstalk through extracellular vesicles may help sustain persistent immune activation and residual viral activities during suppressed HIV infection.
Topics: Humans; HIV Infections; Monocytes; Macrophages; Inflammation; Extracellular Vesicles
PubMed: 36802000
DOI: 10.1093/jleuko/qiac021 -
European Neuropsychopharmacology : the... Aug 2023Clozapine presents immunoregulatory properties not well understood. To address this issue, we performed this systematic review to evaluate the immune alterations induced... (Meta-Analysis)
Meta-Analysis Review
Clozapine presents immunoregulatory properties not well understood. To address this issue, we performed this systematic review to evaluate the immune alterations induced by clozapine and its relationship with the drug's clinical response and compare it with other antipsychotics. Our systematic review has selected nineteen studies meeting the inclusion criteria, from which eleven were included in the meta-analysis, totalizing 689 subjects distributed over three different comparisons. The results revealed that clozapine treatment activates the compensatory immune-regulatory system (CIRS) (Hedges's g = +1.049; CI +0.62 - +1.47, p < 0.001) but has no effects on the immune-Inflammatory Response System (IRS) (Hedges's g= -0.27; CI -1.76 - +1.22, p = 0.71), M1 macrophage (Hedges's g= -0.32; CI -1.78 - +1.14, p = 0.65) and Th1 (Hedge's g = 0.86; CI -0.93 - +1.814, p = 0.07) profiles. Comparing clozapine-treated patients with other anti-psychotics-treated, plasma levels of interleukin (IL)-6 were greater in the clozapine group (Hedge's g = 0.75; CI 0.35 - 1.15, p<0.001). In addition, higher IL-6 plasma levels after four weeks of clozapine treatment were related to the development of clozapine-induced fever; however, IL-6 levels recovered to baseline in 6-10 weeks due to an unexplained compensatory mechanism. In conclusion, our results show that clozapine treatment causes a time-dependent mixed immune profile characterized by increased IL-6 levels and CIRS activation, which may contribute to this drug mechanism of action and adverse effects. Future studies must be designed to investigate the relationship between clozapine-induced immune alterations and symptom remission, treatment resistance, and adverse effects, given the importance of this drug for treating resistant schizophrenia.
Topics: Humans; Clozapine; Schizophrenia; Interleukin-6; Antipsychotic Agents; Oxidative Stress
PubMed: 37148631
DOI: 10.1016/j.euroneuro.2023.04.003