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Frontiers in Immunology 2022Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages...
Cardiovascular diseases, the notorious killer, are mainly caused by atherosclerosis (AS) characterized by lipids, cholesterol, and iron overload in plaques. Macrophages are effector cells and accumulate to the damaged and inflamed sites of arteries to internalize native and chemically modified lipoproteins to transform them into cholesterol-loaded foam cells. Foam cell formation is determined by the capacity of phagocytosis, migration, scavenging, and the features of phenotypes. Macrophages are diverse, and the subsets and functions are controlled by their surrounding microenvironment. Generally, macrophages are divided into classically activated (M1) and alternatively activated (M2). Recently, intraplaque macrophage phenotypes are recognized by the stimulation of CXCL4 (M4), oxidized phospholipids (Mox), hemoglobin/haptoglobin complexes [HA-mac/M(Hb)], and heme (Mhem). The pro-atherogenic or anti-atherosclerotic phenotypes of macrophages decide the progression of AS. Besides, apoptosis, necrosis, ferroptosis, autophagy and pyrotopsis determine plaque formation and cardiovascular vulnerability, which may be associated with macrophage polarization phenotypes. In this review, we first summarize the three most popular hypotheses for AS and find the common key factors for further discussion. Secondly, we discuss the factors affecting macrophage polarization and five types of macrophage death in AS progression, especially ferroptosis. A comprehensive understanding of the cellular and molecular mechanisms of plaque formation is conducive to disentangling the candidate targets of macrophage-targeting therapies for clinical intervention at various stages of AS.
Topics: Atherosclerosis; Foam Cells; Humans; Macrophage Activation; Macrophages; Plaque, Atherosclerotic
PubMed: 35432323
DOI: 10.3389/fimmu.2022.843712 -
Arthritis & Rheumatology (Hoboken, N.J.) Apr 2022To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ)...
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
OBJECTIVE
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
METHODS
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
CONCLUSION
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Topics: Arthritis, Juvenile; Humans; Quality of Life; Rheumatology; Temporomandibular Joint; Temporomandibular Joint Disorders; United States; Uveitis
PubMed: 35233993
DOI: 10.1002/art.42037 -
Arthritis Care & Research Apr 2022To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ)...
2021 American College of Rheumatology Guideline for the Treatment of Juvenile Idiopathic Arthritis: Therapeutic Approaches for Oligoarthritis, Temporomandibular Joint Arthritis, and Systemic Juvenile Idiopathic Arthritis.
OBJECTIVE
To provide updated guidelines for pharmacologic management of juvenile idiopathic arthritis (JIA), focusing on treatment of oligoarthritis, temporomandibular joint (TMJ) arthritis, and systemic JIA with and without macrophage activation syndrome. Recommendations regarding tapering and discontinuing treatment in inactive systemic JIA are also provided.
METHODS
We developed clinically relevant Patient/Population, Intervention, Comparison, and Outcomes questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation approach was used to rate the quality of evidence (high, moderate, low, or very low). A Voting Panel including clinicians and patients/caregivers achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
RESULTS
Similar to those published in 2019, these JIA recommendations are based on clinical phenotypes of JIA, rather than a specific classification schema. This guideline provides recommendations for initial and subsequent treatment of JIA with oligoarthritis, TMJ arthritis, and systemic JIA as well as for tapering and discontinuing treatment in subjects with inactive systemic JIA. Other aspects of disease management, including factors that influence treatment choice and medication tapering, are discussed. Evidence for all recommendations was graded as low or very low in quality. For that reason, more than half of the recommendations are conditional.
CONCLUSION
This clinical practice guideline complements the 2019 American College of Rheumatology JIA and uveitis guidelines, which addressed polyarthritis, sacroiliitis, enthesitis, and uveitis. It serves as a tool to support clinicians, patients, and caregivers in decision-making. The recommendations take into consideration the severity of both articular and nonarticular manifestations as well as patient quality of life. Although evidence is generally low quality and many recommendations are conditional, the inclusion of caregivers and patients in the decision-making process strengthens the relevance and applicability of the guideline. It is important to remember that these are recommendations. Clinical decisions, as always, should be made by the treating clinician and patient/caregiver.
Topics: Antirheumatic Agents; Arthritis, Juvenile; Glucocorticoids; Humans; Quality of Life; Rheumatology; Temporomandibular Joint; Temporomandibular Joint Disorders; United States; Uveitis
PubMed: 35233986
DOI: 10.1002/acr.24853 -
Frontiers in Immunology 2022Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that...
Calcium oxalate nephrolithiasis is a common and highly recurrent disease in urology; however, its precise pathogenesis is still unknown. Recent research has shown that renal inflammatory injury as a result of the cell-crystal reaction plays a crucial role in the development of calcium oxalate kidney stones. An increasing amount of research have confirmed that inflammation mediated by the cell-crystal reaction can lead to inflammatory injury of renal cells, promote the intracellular expression of NADPH oxidase, induce extensive production of reactive oxygen species, activate NLRP3 inflammasome, discharge a great number of inflammatory factors, trigger inflammatory cascading reactions, promote the aggregation, nucleation and growth process of calcium salt crystals, and ultimately lead to the development of intrarenal crystals and even stones. The renal tubular epithelial cells (RTECs)-crystal reaction, macrophage-crystal reaction, calcifying nanoparticles, endoplasmic reticulum stress, autophagy activation, and other regulatory factors and mechanisms are involved in this process.
Topics: Endoplasmic Reticulum Stress; Epithelial Cells; Humans; Inflammasomes; Inflammation; NLR Family, Pyrin Domain-Containing 3 Protein; Nephrolithiasis; Reactive Oxygen Species
PubMed: 35154136
DOI: 10.3389/fimmu.2022.818625 -
Cureus Oct 2021Among the autoimmune (AI) diseases, systemic lupus erythematosus (SLE) is known to mimic various disease processes and this can lead to under-diagnosis of macrophage... (Review)
Review
Among the autoimmune (AI) diseases, systemic lupus erythematosus (SLE) is known to mimic various disease processes and this can lead to under-diagnosis of macrophage activation syndrome (a dire complication). We aimed at performing a systematic review to identify trigger factors that could lead to the development of macrophage activation syndrome (MAS) in patients with SLE as well as identify factors that can affect mortality. We searched the following databases to extract relevant articles: PubMed, ScienceDirect, Cochrane library, Pro-Quest, and Google Scholar. We used search terms including but not limited to hemophagocytic syndromes OR hemophagocytic lymphohistiocytosis OR macrophage activation syndrome OR HLH OR secondary hemophagocytic lymphohistiocytosis AND systemic lupus erythematosus OR SLE. We screened the articles first by titles and abstracts and later by full text. After the application of our eligibility criteria, we identified eight studies to include in our final synthesis. The studies showed that lupus flare itself, as well as, time to onset and high systemic lupus erythematosus disease activity index (SLEDAI) scores, were major risk factors that led to the development of MAS. In addition, infections followed by drugs, underlying malignancy, and pregnancy were other potential trigger factors identified. Studies also detected that MAS development led to high intensive care unit (ICU) admissions and in-hospital mortalities with C-reactive protein (CRP) levels, age, presence of infection, leukopenia, thrombocytopenia, MAS throughout the hospital stay, and high liver function tests (LFTs) as signs of poor prognosis. Additionally, ferritin levels, LFTs, and triglyceride levels formed an important part of diagnostic criteria. However, our review was limited due to the absence of prospective studies and heterogeneity in the studies seen. More studies need to be done to identify various factors leading to hemophagocytic lymphohistiocytosis (HLH) in autoimmune diseases with validated criteria for MAS secondary to autoimmune diseases.
PubMed: 34804679
DOI: 10.7759/cureus.18822 -
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 -
Clinical Immunology (Orlando, Fla.) Sep 2021The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate...
INTRODUCTION
The Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe COVID-19, however clinical outcome data is inconclusive.
OBJECTIVE
To evaluate the clinical outcomes of BTK inhibitors (BTKinibs) in patients with COVID-19.
EVIDENCE REVIEW
We searched PubMed, Embase, and Web of Science:Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.
FINDINGS
125 articles were identified, 6 of which met inclusion criteria. The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs.
CONCLUSIONS AND RELEVANCE
BTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration.
PubMed: 34352390
DOI: 10.1016/j.clim.2021.108816 -
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 -
Obesity Reviews : An Official Journal... Sep 2021This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and... (Review)
Review
The association of soluble CD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus and its underlying physiological disorders: A systematic review.
This systematic review investigates the association of sCD163, a novel biomarker of macrophage activation, with type 2 diabetes mellitus (T2DM), insulin resistance, and beta-cell dysfunction. Sixteen studies (seven cross-sectional, two case-control, one nested case-control, three prospective cohort, and three experimental) were identified. Most studies demonstrated that elevated sCD163 concentrations were associated with increased insulin resistance. Cross-sectional, case-control, and nested case-control studies showed higher sCD163 in subjects with T2DM compared with healthy individuals. An 18-year follow-up prospective cohort study showed that elevated baseline sCD163 was a strong predictor of T2DM incidence. Prospective cohort studies demonstrated that baseline measures and longitudinal changes in sCD163 were positively associated with insulin resistance; however, associations with beta-cell function were inconsistent. Two experimental studies evaluated the relationship of sCD163 with T2DM and HOMA-IR after weight-reducing interventions. After very low-calorie diet treatments, sCD163 concentration declined significantly in patients with T2DM but was not associated with insulin resistance. Bariatric surgery did not significantly impact sCD163 levels. In a double-blind randomized controlled trial, resveratrol supplementation significantly reduced circulating sCD163 in T2DM patients. Current studies demonstrate the potential utility of sCD163 as an early biomarker of T2DM risk and highlight a potential mechanism linking obesity with T2DM onset.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Macrophage Activation; Prospective Studies; Randomized Controlled Trials as Topic; Receptors, Cell Surface
PubMed: 33913230
DOI: 10.1111/obr.13257 -
Research Square Mar 2021ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against...
ImportanceThe Bruton tyrosine kinase (BTK) regulates B cell and macrophage signaling, development, survival, and activation. BTK inhibition was shown to protect against lethal influenza-induced acute lung injury in mice. Inhibiting BTK has been hypothesized to ameliorate lung injury in patients with severe coronavirus disease 2019 (COVID-19). ObjectiveTo evaluate the use of BTK inhibitors (BTKinibs) during COVID-19 and assess how they may affect patient outcomes.Evidence ReviewWe searched PubMed, Embase, and Web of Science: Core on December 30, 2020. Clinical studies with at least 5 COVID-19 patients treated with BTKinibs were included. Case reports and reviews were excluded.FindingsOne hundred twenty-five articles were identified, 6 of which met inclusion criteria. Sample size ranged from 6 to 126 patients. Patient populations included subjects hospitalized with COVID-19 (6/6) and admitted to the intensive care unit (5/6). Patient age ranged between 35 and 98 years. Four studies included patients already receiving BTKinibs for their lymphoproliferative disease, 1 for Waldenstrom's macroglobulinemia and 3 for chronic lymphocytic leukemia (CLL). The most common clinical outcomes measured were oxygen requirements (4/6) and hospitalization rate or duration (3/6). Differences in standard-of-care reflected the date of study and pre-existing conditions in the various patient cohorts. Full-dose acalabrutinib was evaluated in 2 studies, one study evaluated full-dose ibrutinib, and another study evaluated both ibrutinib and acalabrutinib. The remainder 2 studies described outcomes in CLL patients on multiple BTKinibs and other CLL-targeted treatments. Three studies showed decreased oxygen requirements in patients who started or continued BTKinibs. All three studies that evaluated hospitalization rate or duration found favorable outcomes in those on BTKinibs. Conclusions and RelevanceBTKinib use was associated with decreased oxygen requirements and decreased hospitalization rates and duration. However, randomized clinical trials are needed to validate the beneficial effects of BTKinibs for acute SARS-CoV-2 infection.
PubMed: 33791689
DOI: 10.21203/rs.3.rs-319342/v1