scholarly journals SOLUBLE ST2 AND CD163 AS POTENTIALBIOMARKERS TO DIFFERENTIATE PRIMARY HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS FROM MACROPHAGE ACTIVATION SYNDROME

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhuo Gao ◽  
Yini Wang ◽  
Jingshi Wang ◽  
Jia Zhang ◽  
Zhao Wang
Keyword(s):  
Healthy Subjects ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Serum Levels ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Soluble St2 ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ ◽  
Activation Syndrome

Abstract Background and Objective: The differentiation of primary haemophagocytic lymphohistiocytosis (pHLH) and macrophage activation syndrome (MAS) poses a challenge to hematologists. The aim of this study was (1) to compare the levels of soluble ST2 (sST2), sCD163, IL-10, IFN-γ, TNF-α and IL-18 in patients with pHLH and MAS and (2) to investigate whether they can help differentiate the two diseases. Methods: A total of 54 participants were recruited in this study, including 12 pHLH patients, 22 MAS patients and 20 healthy subjects. We measured the levels of sST2 and sCD163 in serum by ELISA. The serum levels of IL-10, IFN-γ, TNF-α and IL-18 were detected using a Luminex 200 instrument. Results: The serum levels of sST2 and sCD163 in MAS patients were markedly higher than that in pHLH patients (363.13 ± 307.24 ng/ml vs 80.75 ± 87.04 ng/ml, P = 0.004; 3532.72 ± 2479.68 ng/ml vs 1731.96 ± 1262.07 ng/ml, P = 0.046). There was no significant difference in the expression of IFN-γ (306.89 ± 281.60 pg/ml vs 562.43 ± 399.86 pg/ml), IL-10 (20.40 ± 30.49 pg/ml vs 8.3 ± 13.14 pg/ml), IL-18 (463.33 ± 597.04 pg/ml vs 1247.82 ± 1318.58 pg/ml) and TNF-α (61.48 ± 84.69 pg/ml vs 106.10 ±77.21 pg/ml) between pHLH and MAS. Conclusion: Patients with pHLH and MAS show some differences in cytokine profiles. The elevated levels of IFN-γ, IL-10, IL-18 and TNF-α can contribute to the diagnosis of HLH, but may not discriminate pHLH from MAS. Levels of sST2 and sCD163 may serve as markers to distinguish pHLH from MAS.

scholarly journals Alteration of Serum Levels of Cytokines in Schizophrenic Patients before and after Treatment with Risperidone

2019 ◽  
Author(s):  
Esfandiar Azizi ◽  
Ahmad Zavaran Hosseini ◽  
Sara Soudi ◽  
Ahmad Ali Noorbala
Keyword(s):  
Healthy Subjects ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Syndrome Scale ◽  
Tnf Α ◽  
Significant Difference ◽  
Before And After ◽  
Schizophrenic Patients ◽  
Ifn Γ

A growing body of evidence suggests the existence of abnormalities in the immune system of schizophrenic patients. The current study examined serum levels of interleukin (IL) -1β, IL-6, IL-2,interferon(IFN) -γ, and tumor necrosis factor(TNF)-α in schizophrenic patients before and after treatment with risperidone and correlated levels of these cytokines with symptomatology. The study group consisted of 24 schizophrenic patients as defined by Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) criteria and 24 healthy controls. Serum cytokine levels were examined using enzyme-linked immunosorbent assay (ELISA). Schizophrenic symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) questionnaire. The serum levels of TNF-α, IL-1β and IL-6 were significantly higher in participants before treatment compared with the healthy controls and after treatment (p<0.001). IFN-γ and IL-2 levels were significantly lower in participants after treatment compared with before treatment and the healthy controls (p<0.001). Except for IL-6 (p<0.05), there was no significant difference in the levels of TNF-α and IL-1β between the patients receiving treatment and the healthy subjects. Moreover, there was no significant difference in levels of IFN-γ and IL-2 between patients before treatment and the healthy subjects. There were no significant correlations between the concentration of cytokines studied and the PANSS. Positive intercorrelations between the production of IFN-γ and IL-2 were detected for sums of all groups(r=0.33, p=0.005). Clinical improvement of treated patients was associated with a reduction in the studied cytokines. It seems that changes in the cytokines level may play a significant role in the psychopathology of these patients.

Macrophage activation syndrome: characteristic findings on liver biopsy illustrating the key role of activated, IFN-γ-producing lymphocytes and IL-6- and TNF-α-producing macrophages

Blood ◽  
2005 ◽  
Vol 105 (4) ◽  
pp. 1648-1651 ◽  
Author(s):  
An D. Billiau ◽  
Tania Roskams ◽  
Rita Van Damme-Lombaerts ◽  
Patrick Matthys ◽  
Carine Wouters
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Interferon Γ ◽  
Effector Pathway ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor ◽  
Activation Syndrome

Abstract Macrophage activation syndrome (MAS) is a rare and potentially fatal disorder, thought to result from uncontrolled activation and proliferation of T cells and excessive activation of macrophages. The term MAS designates a clinicopathologic entity that occurs in different hemophagocytic syndromes (HSs). Primary hemophagocytic lymphohistiocytosis (HLH) is recognized to have an immunogenetic basis, but in the secondary HS (also referred to as secondary HLH), the cause is unknown. The pathogenesis of the accelerated disease phase typical of MAS remains incompletely understood. This report describes the immunohistochemical findings on liver tissues from 5 children, each of whom presented with MAS in the context of a different type of HS. The data provide direct evidence for the involvement of activated CD8+ lymphocytes through the production of interferon-γ and of macrophages through hemophagocytosis and production of interleukin 6 and tumor necrosis factor-α, and underscore the view that MAS in different HSs share a common effector pathway. (Blood. 2005;105:1648-1651)

scholarly journals OP0313 PRELIMINARY CRITERIA FOR MACROPHAGE ACTIVATION SYNDROME ASSOCIATED WITH CORONAVIRUS DISEASE-19

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 191.1-192
Author(s):  
S. Amikishiyev ◽  
M. G. Gunver ◽  
M. Bektas ◽  
S. Aghamuradov ◽  
B. Ince ◽  
...  
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Laboratory Data ◽  
Disease Onset ◽  
Dynamic Changes ◽  
Ferritin Concentration ◽  
Neutrophil Lymphocyte Ratio ◽  
Significant Difference ◽  
D Dimer ◽  
Activation Syndrome

Background:COVID-19 runs a severe disease associated with acute respiratory distress syndrome in a subset of patients, and a hyperinflammatory response developing in the second week contributes to the worse outcome. Inflammatory features are mostly compatible with macrophage activation syndrome (MAS) observed in other viral infections despite resulting in milder changes. Early detection and treatment of MAS may be associated with a better outcome. However, available criteria for MAS associated with other causes have not been helpful.Objectives:To identify distinct features of MAS associated with COVID-19 using a large database enabling to assess of dynamic changes.Methods:PCR-confirmed hospitalized COVID-19 patients followed between March and September 2020 constituted the discovery set. Patients considered to have findings of MAS by experienced physicians and given anakinra or tocilizumab were classified as the MAS group and the remaining patients as the non-MAS group. The MAS group was then re-grouped as the cases with exact-MAS and borderline-MAS cases by the study group. Clinical and laboratory data including the Ct values of the PCR test were obtained from the database, and dynamic changes were evaluated especially for the first 14 days of the hospitalization. The second set of 162 patients followed between September-December 2020 were used as the replication group to test the preliminary criteria. In the second set, hospitalization rules were changed, and all patients required oxygen support and received dexamethasone 6mg/day or equivalent glucocorticoids. Daily changes were calculated for the laboratory items in MAS, borderline, and non-MAS groups to see the days differentiating the groups, and ROC curves and lower and upper limits (10-90%) of the selected parameters were calculated to determine the cutoff values.Results:A total of 769 PCR-confirmed hospitalized patients were analysed, and 77 of them were classified as MAS and 83 as borderline MAS patients. There was no statistically significant difference in the baseline viral loads of MAS patients compared to the non-MAS group according to the Ct values. Daily dynamic changes in the MAS group differed from the non-MAS group especially around the 6th day of hospitalization, and more than a twofold increase in ferritin and a 1.5-fold increase in D-dimer levels compared to the baseline values help to define the MAS group. Twelve items selected for the criteria are given in Table 1 below. The total score of 45 provided 79.6% sensitivity for the MAS (including borderline cases) and 81.3% specificity around days 5 and 6 in the discovery set, and a score of 60 increased the specificity to 94.9% despite a decrease in sensitivity to 40.8%. The same set provided a similar sensitivity (80.3%) in the replication, but a lower specificity (47.4-66% on days 6 to 9) due to a group of control patients with findings of MAS possibly masked by glucocorticoids.Table 1.Preliminary Criteria for Macrophage Activation Syndrome Associated with Coronavirus Disease-191.Fever (>37.0 °C)2.Ferritin concentration > 550 ng/mL3.More than 2 times increase of ferritin concentration within 7 days of disease onset4.Neutrophil count > 6000 cell/mm35.Lymphopenia < 1000 cell/mm36.Neutrophil/lymphocyte ratio > 67.D-dimer concentration > 1000 ng/ml8.More than 50% increase of D-dimer concentration within 7 days of disease onset9.CRP concetration > 50 mg/L10.LDH concentration > 300 U/L11.ALT or AST concentration > 50 U/L12.Procalcitonin concentration < 1.21 point for each positive item assessed on Days 5-7Score calculation: Total points / 12 x 100Possible MAS ≥45 and Definite MAS ≥60Conclusion:This study defined a set of preliminary criteria using the most relevant items of MAS according to the dynamic changes in the parameters in a group of COVID-19 patients. A score of 45 would be helpful to define a possible MAS group with reasonable sensitivity and specificity to start necessary treatments as early as possible.Disclosure of Interests:None declared.

scholarly journals Neutralization of IFN-γ reverts clinical and laboratory features in a mouse model of macrophage activation syndrome

2018 ◽  
Vol 141 (4) ◽  
pp. 1439-1449 ◽  
Author(s):  
Giusi Prencipe ◽  
Ivan Caiello ◽  
Antonia Pascarella ◽  
Alexei A. Grom ◽  
Claudia Bracaglia ◽  
...  
Keyword(s):  
Mouse Model ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Laboratory Features ◽  
Ifn Γ ◽  
Activation Syndrome

scholarly journals Macrophage activation syndrome/haemophagocytic lymphohistiocytosis secondary to Burkholderia cepacia complex septicaemia in an elderly female carrier of X-linked chronic granulomatous disease with extreme lyonisation: ‘cepacia syndrome’ revisited

2019 ◽  
Vol 12 (8) ◽  
pp. e230434 ◽  
Author(s):  
Nicolás Urriola ◽  
Andrew Williams ◽  
Karuna Keat
Keyword(s):  
Chronic Granulomatous Disease ◽  
Burkholderia Cepacia ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Burkholderia Cepacia Complex ◽  
Female Carrier ◽  
Granulomatous Disease ◽  
Haemophagocytic Lymphohistiocytosis ◽  
Stimulating Factor ◽  
Activation Syndrome

X-linked carriers of chronic granulomatous disease (CGD) may become phenotypically affected if substantial skewing from lyonisation occurs. We describe a 73-year-old female carrier with an overt CGD phenotype due to skewed lyonisation, complicated by macrophage activation syndrome (MAS)/haemophagocytic lymphohistiocytosis (HLH) secondary to Burkholderiacepacia complex septicaemia that was successfully treated with a combination of three antibiotics, an antifungal, granulocyte colony stimulating factor, intravenous immune globulin (IVIG) and ciclosporin. Fully phenotypic immunodeficiency is possible in X-linked CGD carriers when skewed lyonisation occurs, rendering such patients to all the same sequelae of CGD such as MAS/HLH. MAS/HLH should be thoroughly excluded when evaluating ‘cepacia syndrome’ in non-CGD patients.

Monocyte and bone marrow macrophage transcriptional phenotypes in systemic juvenile idiopathic arthritis reveal TRIM8 as a mediator of IFN-γ hyper-responsiveness and risk for macrophage activation syndrome

2020 ◽  
pp. annrheumdis-2020-217470
Author(s):  
Grant S Schulert ◽  
Alex V Pickering ◽  
Thuy Do ◽  
Sanjeev Dhakal ◽  
Ndate Fall ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Rna Seq ◽  
Bone Marrow Macrophage ◽  
Ifn Γ ◽  
Activation Syndrome

ObjectivesSystemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening cytokine storm driven by interferon (IFN)-γ. SJIA monocytes display IFN-γ hyper-responsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte and bone marrow macrophage (BMM) polarisation phenotypes in SJIA including molecular features contributing to IFN response.MethodsBulk RNA-seq was performed on peripheral blood monocytes (n=26 SJIA patients) and single cell (sc) RNA-seq was performed on BMM (n=1). Cultured macrophages were used to define consequences of tripartite motif containing 8 (TRIM8) knockdown on IFN-γ signalling.ResultsBulk RNA-seq of SJIA monocytes revealed marked transcriptional changes in patients with elevated ferritin levels. We identified substantial overlap with multiple polarisation states but little evidence of IFN-induced signature. Interestingly, among the most highly upregulated genes was TRIM8, a positive regulator of IFN-γ signalling. In contrast to PBMC from SJIA patients without MAS, scRNA-seq of BMM from a patient with SJIA and MAS identified distinct subpopulations of BMM with altered transcriptomes, including upregulated IFN-γ response pathways. These BMM also showed significantly increased expression of TRIM8. In vitro knockdown of TRIM8 in macrophages significantly reduced IFN-γ responsiveness.ConclusionsMacrophages with an ‘IFN-γ response’ phenotype and TRIM8 overexpression were expanded in the bone marrow from an MAS patient. TRIM8 is also upregulated in SJIA monocytes, and augments macrophage IFN-γ response in vitro, providing both a candidate molecular mechanism and potential therapeutic target for monocyte hyper-responsiveness to IFNγ in cytokine storms including MAS.

Cytokine Profiles of Macrophage Activation Syndrome Associated with Rheumatic Diseases

2010 ◽  
Vol 37 (5) ◽  
pp. 967-973 ◽  
Author(s):  
JUNKO MARUYAMA ◽  
SHIGEKO INOKUMA
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Laboratory Data ◽  
Serum Levels ◽  
Interferon Γ ◽  
Cytokine Profiles ◽  
Factor Α ◽  
Activation Syndrome

Objective.To elucidate the cytokine profiles of macrophage activation syndrome (MAS) in relation to underlying rheumatic diseases and prognosis.Methods.The clinical features and laboratory data of 18 patients with MAS and rheumatic diseases were retrospectively analyzed. Serum levels of macrophage colony-stimulating factor (M-CSF), interleukin 18 (IL-18), tumor necrosis factor-α, interleukin 6, interferon-γ, ferritin, and ß2-microglobulin (ß2m) were measured. These data were compared between underlying diseases and between those who died and those who recovered.Results.Of the 18 patients with MAS, 9 had underlying systemic lupus erythematosus (SLE), 7 had adult-onset Still’s disease (AOSD), 1 had rheumatoid arthritis (RA), and 1 had antiphospholipid syndrome. Three patients with SLE and 1 patient with RA died. The serum M-CSF and IL-18 levels were substantially elevated in all the patients. In the patients with SLE, the M-CSF level was higher than the IL-18 level (median: 4879 vs 1341 pg/ml, p = 0.0054), and it was the reverse in the patients with AOSD (5883 vs 228,350 pg/ml, p = 0.0017). The serum M-CSF and ß2m levels were significantly higher in the patients who died than in those who recovered (M-CSF: 18,245 vs 3404 pg/ml, p = 0.019; ß2m: 18.8 vs 5.4 mg/dl, p = 0.0058).Conclusion.The cytokine profiles associated with MAS differed between patients with SLE and patients with AOSD. The patients with SLE showed a prominent increase in serum M-CSF levels, as did the patients with AOSD in serum IL-18 level. Patients who died had higher serum M-CSF and ß2m levels, and this suggests that aggressive treatment for patients with MAS and these profiles should be promptly started.

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