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International Immunopharmacology Jun 2024To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients. (Review)
Review
OBJECTIVE
To evaluate the efficacy and safety of Janus kinases inhibitors (JAKi) for adult-onset Still's disease (AOSD) patients.
METHODS
We searched the Embase, PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and the China National Knowledge Infrastructure (CNKI) from inception up to 22 October 2023. The results were supplemented by a backward search of relevant publications. Two authors independently selected trials. The available studies were comprehensively reviewed and analysed.
RESULTS
A total of 9 studies with a total of 35 patients were included in the review. Of these patients, 17 (48.6%) patients were treated with tofacitinib, 14 (40%) with baricitinib, 4 (11.4%) with ruxolitinib and 1 (2.9%) with upadacitinib. After treatment with JAKi, 17 (48.6%) patients showed complete remission, 12 (34.3%) patients showed partial remission, and 7 (20%) patients showed loss of efficacy or relapse. The use of ruxolitinib showed a remission rate of 100% in AOSD patients with macrophage activation syndrome (MAS). The incidence of adverse events (AEs) reported were mild and rare overall. Most AEs were abnormal lipid parameters (9.7%), bacterial pneumonia (3.2%), organised pneumonia (3.2%), diarrhoea (3.2%), increased heart rate (3.2%), menometrorrhagia (3.2%) and leukopenia (3.2%). One patient died from bacterial pneumonia.
CONCLUSION
JAKi therapy may be an option for patients with AOSD, especially for refractory AOSD. For patients with AOSD complicated by MAS, ruxolitinib seems to be a better choice than other JAKi agents. Although our study shows that JAKi are well tolerated in AOSD patients, we still need to be on the lookout for fatal infections.
PubMed: 38870881
DOI: 10.1016/j.intimp.2024.112451 -
Modern Rheumatology May 2024This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
OBJECTIVES
This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS
Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan.
RESULTS
Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases.
CONCLUSIONS
Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.
PubMed: 38753302
DOI: 10.1093/mr/roae046 -
Frontiers in Immunology 2024Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH...
BACKGROUND
Hemophagocytic Lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by a severe impairment of the immune homeostasis. While Familial-HLH (FHL) is a known cause, the involvement of other Inborn Errors of Immunity (IEI) in pediatric-HLH remains understudied.
OBJECTIVE
This systematic review aimed to assess the clinical features, triggers, laboratory data, treatment, and outcomes of pediatric HLH patients with IEI other than FHL (IEInotFHL), emphasizing the importance of accurate identification and management.
METHODS
A systematic search for studies meeting inclusion criteria was conducted in PubMed, EMBASE, MEDLINE, and Cochrane Central. Quality assessment was performed through JBI criteria.
RESULTS
A comprehensive search yielded 108 records meeting inclusion criteria, involving 178 patients. We identified 46 different IEI according to IUIS 2022 Classification. Combined immunodeficiencies, immune dysregulation disorders, and phagocyte defects were the IEI most frequently associated with HLH. In 75% of cases, HLH preceded the IEI diagnosis, often with an unrecognized history of severe infections. Triggers reflected the specific infection susceptibilities within IEI groups. Liver and central nervous system involvement were less common than in FHL cases. Treatment approaches and outcomes varied, with limited long-term follow-up data, limiting the assessment of therapeutic efficacy across IEI groups.
CONCLUSION
A comprehensive evaluation encompassing immunological, infectious, and genetic aspects is essential in pediatric-HLH. Relying solely on FHL or EBV susceptibility disorders tests is insufficient, as diverse other IEI can contribute to HLH. Early recognition of HLH as a potential warning sign can guide timely diagnostic investigations and facilitate tailored therapeutic interventions for improved outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=371425, PROSPERO, CRD42022371425.
Topics: Child; Humans; Disease Susceptibility; Homeostasis; Lymphohistiocytosis, Hemophagocytic; Immune System Diseases
PubMed: 38415256
DOI: 10.3389/fimmu.2024.1282804 -
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 -
Journal of Autoimmunity Feb 2021The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the...
The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the initial target of SARS-CoV-2 is the respiratory tract, it is becoming increasingly clear that there is a complex interaction between the virus and the immune system ranging from mild to controlling responses to exuberant and dysfunctional multi-tissue directed autoimmune responses. The immune system plays a dual role in COVID-19, being implicated in both the anti-viral response and in the acute progression of the disease, with a dysregulated response represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinflammation. It has been speculated that these immunological changes may induce the loss of tolerance and/or trigger chronic inflammation. In particular, molecular mimicry, bystander activation and epitope spreading are well-established proposed mechanisms to explain this correlation with the likely contribution of HLA alleles. We performed a systematic literature review to evaluate the COVID-19-related autoimmune/rheumatic disorders reported between January and September 2020. In particular, we investigated the cases of incident hematological autoimmune manifestations, connective tissue diseases, antiphospholipid syndrome/antibodies, vasculitis, Kawasaki-like syndromes, acute arthritis, autoimmune-like skin lesions, and neurologic autoimmune conditions such as Guillain-Barré syndrome. We screened 6263 articles and report herein the findings of 382 select reports which allow us to conclude that there are 2 faces of the immune response against SARS-CoV-2, that include a benign virus controlling immune response and a many faceted range of dysregulated multi-tissue and organ directed autoimmune responses that provides a major challenge in the management of this viral disease. The number of cases for each disease varied significantly while there were no reported cases of adult onset Still disease, systemic sclerosis, or inflammatory myositis.
Topics: Animals; Autoimmune Diseases; COVID-19; Chronic Disease; Humans; Immunity; Incidence; Inflammation; Janus Kinases; SARS-CoV-2
PubMed: 33401171
DOI: 10.1016/j.jaut.2020.102592 -
Journal of Clinical Medicine Apr 2023Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset...
INTRODUCTION
Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity.
METHODS
We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment.
RESULTS
Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis.
CONCLUSIONS
JAKi represent a promising option in the treatment of lung disease associated with sJIA.
PubMed: 37048785
DOI: 10.3390/jcm12072702 -
SN Comprehensive Clinical Medicine 2021With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are...
UNLABELLED
With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries ( < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C.
SUPPLEMENTARY INFORMATION
The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.
PubMed: 33432304
DOI: 10.1007/s42399-020-00690-6 -
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 -
Journal of Musculoskeletal & Neuronal... Mar 2021Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown.
METHODS
To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG's PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores.
RESULTS
The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma.
CONCLUSIONS
This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Neoplasms; Databases, Genetic; Gene Regulatory Networks; Humans; Immunity, Cellular; Macrophages; Osteosarcoma; Prognosis; Protein Array Analysis; Receptors, Cell Surface; Tumor Microenvironment
PubMed: 33657763
DOI: No ID Found -
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