scholarly journals Multidimensional inflammatory and immunological endotypes of idiopathic focal and segmental glomerulosclerosis and their association with treatment outcomes

2020 ◽  
Author(s):  
Neus Roca ◽  
Alvaro Madrid ◽  
Mercedes Lopez ◽  
Gloria Fraga ◽  
Elias Jatem ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Response To Treatment ◽  
T Helper ◽  
Corticosteroid Resistance ◽  
T Helper Lymphocyte ◽  
Regulatory Lymphocytes ◽  
Lymphocyte Populations ◽  
Cluster 2

Abstract Objectives Idiopathic focal segmental glomeruloesclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients, using a cluster analysis, based on inflammatory and immunological variables and to analyse whether a certain endotype is associated with response to treatment with corticosteroids. Patients and Methods This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble IL-1 receptor, TNFα, IFNγ, IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, Hemopexin, Haptoglobin, suPAR and urinary CD80 were measured with ELISA, or nephelometry. T-helper lymphocyte populations and T regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a K-means cluster analysis was performed. Results 79 FSGS patients were included. Three clusters (CL) were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a Th17 pattern. CL2 (20.2 %) included IL-4, IL-5, IL-13, IgE and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among clusters. 42/79 patients (53.1%) showed corticosteroid-resistance. The prevalence of corticosteroid-resistance was significantly lower in cluster 2 (4/16, 25%) than in clusters 1 (16/26, 72.7%) and 3 (22/41, 53.7%) (p 0.018), with no significant differences between cluster 1 and 3 (p:0.14). Conclusions Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in 3 distinct clusters according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids.

scholarly journals A possible contribution to improving the therapeutic potentials of Babor's Typology of Alcohol Dependent Patients

2015 ◽  
Vol 64 (3) ◽  
pp. 200-206
Author(s):  
Mário Sérgio Ribeiro ◽  
Luiz Cláudio Ribeiro ◽  
Rafael Augusto Ferreira
Keyword(s):  
Cluster Analysis ◽  
Personality Traits ◽  
Clinical Features ◽  
Therapeutic Strategies ◽  
Response To Treatment ◽  
Type B ◽  
Chi Square ◽  
Cluster 2 ◽  
Therapeutic Possibilities ◽  
Alcohol Dependent

ABSTRACT Objective The objective of this study was to replicate Babor's Typology and to explore clinical features related to personality traits that may underlie this classification, in order to improve its therapeutic possibilities. Methods Observational prospective study on a group of 273 male alcoholics. After a replication of Babor's variables, Cluster Analysis, Chi-Square – applied on clinical variables related to a Lappda Tipology – and Kappa tests were performed. Results The study identified two distinct clusters that held similar features to those described for the Type A/Type B classification. Besides presenting a lower socio-economic situation, Cluster 2 patients were associated with higher vulnerability and severe clinical features and also differed from Cluster 1 in their response to treatment. These replicated clusters retained connections and also differences in relation to the variables derived from the Lappda Typology. Conclusion Considering that each of the two replicated clusters seem to be associated to different personality traits – according to their correlations to the affective, cognitive and behavioral dimensions brought forward by the Lappda Typology – it is acceptable that this study may contribute to the development of more comprehensive and effective therapeutic strategies specifically tailored to target more specific personality traits of these subgroups of alcoholic patients.

scholarly journals Echocardiographic phenotypes of patients with sickle cell disease. An unsupervised analysis based on etendard cohort

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
T D"humieres ◽  
J Inamo ◽  
S Deswarte ◽  
T Damy ◽  
G Loko ◽  
...  
Keyword(s):  
Cluster Analysis ◽  
Cardiac Output ◽  
Sickle Cell Disease ◽  
Diastolic Function ◽  
Sickle Cell ◽  
Left Ventricular ◽  
Integrative Approach ◽  
Cell Disease ◽  
Clinical Profiles ◽  
Cluster 2

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): PHRC Backgroung Echocardiography is the cornerstone in the diagnosis of cardiopulmonary involvement in sickle cell disease (SCD). However, given the unique pathophysiology of SCD associating high cardiac output, and various degrees of peripheral vasculopathy, differentiate the pathological from the physiological using echocardiography can be particularly challenging. Purpose This study sought to link cardiac phenotypes in homozygous SCD patients with clinical profiles and outcomes using cluster analysis. Methods We analyzed data of 379 patients with a sufficient echographic dataset included in the French Etendard Cohort, a prospective cohort initially designed to assess the prevalence of pulmonary hypertension. A cluster analysis was performed on echocardiographic variables, and the association between clusters and clinical profiles and outcomes was assessed. Results Three clusters were identified. Cluster 1 (N = 122) patients had the lowest cardiac output, only mild left cavities remodeling, diastolic dysfunction, and high tricuspid regurgitation velocity (TRV). They were predominantly female, as old as cluster 2, and displayed the most severe functional limitation. Cluster 2 (N = 103) patients had the highest cardiac output, left ventricular mass and a severely dilated left atrium. Diastolic function and TRV were similar to cluster 1. These patients had a higher blood pressure and a severe hemolytic anemia. Cluster 3 (N = 154) patients had mild left cavities remodeling, the best diastolic function and the lowest TRV. They were younger patients with the highest hemoglobin and lowest hemolytic markers. Right heart catheterization was performed in 94 patients. Cluster 1 gathered the majority of precapillary PH while cluster 2 gathered postcapillary PH and no PH was found in cluster 3. After a follow-up of 9.9 years (IQR: 9.3 to 10.5 years) death occurred in 38 patients (10%). Clusters 2 had the worst prognosis with 18% mortality rate vs. 12% in cluster 2 and 5% in cluster 1 (P log-rank = 0,02). Results are summarized in the central illustration. Conclusions Cluster analysis of echocardiographic variables identified 3 phenotypes among SCD patients, each associated with different clinical features and outcome. These findings underlines the necessity to rethink echocardiographic evaluation of SCD patients, with an integrative approach based on simultaneous evaluation of TRV along with left cavities remodeling and diastolic parameters. Abstract Figure.

scholarly journals Pattern of inflammatory immune response determines the clinical course and outcome of COVID-19: unbiased clustering analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eunyoung Emily Lee ◽  
Kyoung-Ho Song ◽  
Woochang Hwang ◽  
Sin Young Ham ◽  
Hyeonju Jeong ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Clustering Analysis ◽  
Validation Cohort ◽  
Inflammatory Responses ◽  
Clinical Course ◽  
Severe Disease ◽  
Outcome Data ◽  
Inflammatory Immune Response ◽  
Cluster 2

AbstractThe objective of the study was to identify distinct patterns in inflammatory immune responses of COVID-19 patients and to investigate their association with clinical course and outcome. Data from hospitalized COVID-19 patients were retrieved from electronic medical record. Supervised k-means clustering of serial C-reactive protein levels (CRP), absolute neutrophil counts (ANC), and absolute lymphocyte counts (ALC) was used to assign immune responses to one of three groups. Then, relationships between patterns of inflammatory responses and clinical course and outcome of COVID-19 were assessed in a discovery and validation cohort. Unbiased clustering analysis grouped 105 patients of a discovery cohort into three distinct clusters. Cluster 1 (hyper-inflammatory immune response) was characterized by high CRP levels, high ANC, and low ALC, whereas Cluster 3 (hypo-inflammatory immune response) was associated with low CRP levels and normal ANC and ALC. Cluster 2 showed an intermediate pattern. All patients in Cluster 1 required oxygen support whilst 61% patients in Cluster 2 and no patient in Cluster 3 required supplementary oxygen. Two (13.3%) patients in Cluster 1 died, whereas no patient in Clusters 2 and 3 died. The results were confirmed in an independent validation cohort of 116 patients. We identified three different patterns of inflammatory immune response to COVID-19. Hyper-inflammatory immune responses with elevated CRP, neutrophilia, and lymphopenia are associated with a severe disease and a worse outcome. Therefore, targeting the hyper-inflammatory response might improve the clinical outcome of COVID-19.

scholarly journals Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

2021 ◽  
Vol 22 (15) ◽  
pp. 7856
Author(s):  
Sang Min Lee ◽  
Kyung-No Son ◽  
Dhara Shah ◽  
Marwan Ali ◽  
Arun Balasubramaniam ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cytokine Production ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Mapk Signaling ◽  
Response To Treatment ◽  
No Production ◽  
Inflammatory Signaling ◽  
Raw264.7 Macrophages ◽  
Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

scholarly journals SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Translationally Controlled Tumor Protein ◽  
Biochemical Analyses ◽  
Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

scholarly journals Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Luna-Reyes ◽  
Eréndira G. Pérez-Hernández ◽  
Blanca Delgado-Coello ◽  
Miguel Ángel Ávila-Rodríguez ◽  
Jaime Mas-Oliva
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Glucose Uptake ◽  
Inflammatory Responses ◽  
Serum Levels ◽  
Systemic Inflammatory Response ◽  
Positron Emission ◽  
Inflammatory Molecules ◽  
Circulating Levels ◽  
Lps Treatment

AbstractThe present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase–dependent induction of Socs-3

Blood ◽  
2009 ◽  
Vol 113 (15) ◽  
pp. 3512-3519 ◽  
Author(s):  
Roberta Caruso ◽  
Carmine Stolfi ◽  
Massimiliano Sarra ◽  
Angelamaria Rizzo ◽  
Massimo C. Fantini ◽  
...  
Keyword(s):  
Map Kinase ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Human Peripheral Blood ◽  
Serum Levels ◽  
Cell Types ◽  
P38 Map Kinase ◽  
Negative Regulator ◽  
Therapeutic Implications

Abstract IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down-regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cytokines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase–driven Socs-3–dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cytokines and protected against LPS-induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications.

Evaluation of a gait scoring system for cattle by using cluster analysis and Krippendorff’s α reliability

2018 ◽  
Vol 184 (7) ◽  
pp. 220-220 ◽  
Author(s):  
Nina Volkmann ◽  
Jenny Stracke ◽  
Nicole Kemper
Keyword(s):  
Cluster Analysis ◽  
Dairy Cows ◽  
Scoring System ◽  
Partial Agreement ◽  
Claw Lesions ◽  
Cluster 2 ◽  
Locomotion Score

The aim of the presented study was to validate a three-point locomotion score (LS) classifying lameness in dairy cows. Therefore, locomotion of 144 cows was scored and data on claw lesions were collected during hoof trimming. Based on latter data a cluster analysis was performed to objectively classify cows into three groups (Cluster 1–3). Finally, the congruence between scoring system and clustering was tested using Krippendorff’s α reliability. In total, 63 cows (43.7 per cent) were classified as non-lame (LS1), 38 (26.4 per cent) were rated as LS2 with an uneven gait and 43 (29.9 per cent) cows were ranked as clearly lame (LS3). In comparison, hoof-trimming data revealed 64 cows (44.4 per cent) to show no diagnosis, 37 (25.7 per cent) one diagnosis, 33 animals (22.9 per cent) two diagnoses and 10 (7.0 per cent) more than two. Comparing the respective categorisation received by either the cluster analysis or LS in between groups, a high correspondence (79.4 per cent and 83.7 per cent) could be found for LS1 and cluster 1 as well as for LS3 and cluster 3. Only LS2 had partial agreement (21.1 per cent) to cluster 2. However, Krippendorff’s α was 0.75 (95 per cent CI 0.68 to 0.81), indicating a good degree of reliability. Therefore, the results of this study suggested that the presented LS is suitable for classifying the cows’ state of lameness representing their claw diseases.

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