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UFMylation, a novel ubiquitin-like protein modification system, has been recently found to be activated in inflammation. However, the effects of UFMylation activation on inflammation in vivo remains unclear. In the present study, we generated a UFMylation activated mice using transgenic (TG) techniques. Lipopolysaccharide (LPS) was used to induce systemic inflammation in both TG and non-transgenic (NTG) mice. Serum cytokines were detected using a Mouse Cytokine Array, and the proportions of splenic NK, B and T cells were determined by using flow cytometry. We found that TG mice showed increased serum G-CSF, TNF RII and decreased serum TCA-3, CD30L, bFGF, IL-15 and MIG compared with NTG mice at baseline. Furthermore, serum cytokines in TG mice exhibited different responses to LPS compared to NTG mice. LPS up-regulated serum TNF RII, G-CSF, MCP-5, RANTES, KC, BLC, MIG and down-regulated IL-1b, IL-2, IL-3, IL-4, IL-5, IL-7, IL-10, IL-12p40, IL-15, IL-17, IFN-γ, TCA-3, Eotaxin-2, LIX, MCP-1, TNFα, GM-CSF in NTG mice, whereas LPS up-regulated G-CSF, MCP-5, RANTES, KC, BLC, MIG, ICAM-1, PF4, Eotaxin, CD30L, MIP-1a, TNFRI and down-regulated IL-1b, IL-3, LIX, MCP-1, TNFα, GM-CSF in TG mice. Data from flow cytometry indicated that LPS significantly reduced the percentages of NK and NKT cells in NTG mice, whereas UFMylation activation inhibited LPS-induced NKT cell decrease. The proportions of B cells, total CD4+ and total CD8+ T cells were comparable between TG and NTG mice in response to LPS treatment, whereas the percentages of CD4+CD69+ and CD8+CD69+T cells were lower in TG mice. These findings suggest that UFMylation may alter LPS-induced serum cytokine profile and participate in splenic T cell activation in vivo.
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OBJECTIVES: To evaluate cytokine profiles and interferon-gamma release assay (IGRA) for their diagnostic capabilities in the differentiation of tuberculosis (TB) from non-TB conditions, as well as smear-negative pulmonary tuberculosis (SNPT) from smear-positive pulmonary tuberculosis (SPPT). METHODS: A total of 125 participants were included, 77 of whom had TB and 48 who didn't, and demographic, clinical, and laboratory data were collected, including cytokine levels and IGRA results. The TB patients were further divided into 2 subgroups: SNPT (n=42) and SPPT (n=35). RESULTS: Compared to non-TB, the TB group had lower BMI, higher WBC, neutrophils, monocytes, ESR and CRP (p<0.05). TB patients showed higher IL-2, IL-6, IFN-γ, IL-8 (p<0.001) and higher IGRA positivity (88.3% versus [vs.] 29.2%, p<0.001). Between SNPT and SPPT, moderate effect sizes were observed for IFN-α, IL-2, IL-10, IL-8 (Cohen's d 0.59-0.76), with lower IGRA positivity in SNPT (81.0% vs. 97.1%, p=0.015). ROC analysis indicated IFN-α, IL-2, IL-10, IL-8 had moderate accuracy for SNPT diagnosis (AUCs 0.668-0.734), and combining these improved accuracy (AUC 0.759, 80% sensitivity, 64.2% specificity). CONCLUSION: A multi-biomarker approach combining these cytokines demonstrates enhanced diagnostic accuracy for tuberculosis.
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Citocinas , Tuberculosis Pulmonar , Humanos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/sangre , Masculino , Femenino , Citocinas/sangre , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Ensayos de Liberación de Interferón gamma , Interleucina-2/sangre , Interleucina-8/sangre , Curva ROC , Interleucina-6/sangre , Interleucina-10/sangreRESUMEN
Background: Leukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma gangrenosum (PG)-like skin ulcers (PGLUs) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1. Objective: Our aim was to report the case of a 10-year-old boy presenting with PGLUs as the first manifestation of LAD-1 treated with ustekinumab. Methods: We obtained in situ cytokine profiles. Results: PGLUs were triggered by cutaneous ringworm infection (Trichophyton tonsurans). Skin biopsy samples showed increased intralesional expression of IL-17A, Il-23, and IL-1ß as compared with their expression in healthy controls. After an unsuccessful attempt at treatment with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile. Conclusions: PGLUs, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for patients with LAD-1 and PGLUs while bridging the time until stem cell transplantation.
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The combination of signals from the T-cell receptor (TCR) and co-stimulatory molecules triggers transcriptional programs that lead to proliferation, cytokine secretion, and effector functions. We compared the impact of engaging the TCR with CD28 and/or CD43 at different time points relative to TCR engagement on T-cell function. TCR and CD43 simultaneous engagement resulted in higher CD69 and PD-1 expression levels than in TCR and CD28-stimulated cells, with a cytokine signature of mostly effector, inflammatory, and regulatory cytokines, while TCR and CD28-activated cells secreted all categories of cytokines, including stimulatory cytokines. Furthermore, the timing of CD43 engagement relative to TCR ligation, and to a lesser degree that of CD28, resulted in distinct patterns of expression of cytokines, chemokines, and growth factors. Complete cell activation was observed when CD28 or CD43 were engaged simultaneously with or before the TCR, but ligating the TCR before CD43 or CD28 failed to complete a cell activation program regarding cytokine secretion. As the order in which CD43 or CD28 and the TCR were engaged resulted in different combinations of cytokines that shape distinct T-cell immune programs, we analyzed their upstream sequences to assess whether the combinations of cytokines were associated with different sets of regulatory elements. We found that the order in which the TCR and CD28 or CD43 are engaged predicts the recruitment of specific sets of chromatin remodelers and TFSS, which ultimately regulate T-cell polarization and plasticity. Our data underscore that the combination of co-stimulatory molecules and the time when they are engaged relative to the TCR can change the cell differentiation program.
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Antígenos CD28 , Receptores de Antígenos de Linfocitos T , Antígenos CD28/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Linfocitos T , Activación de Linfocitos , Diferenciación Celular , Citocinas/metabolismoRESUMEN
OBJECTIVE: To explore whether cytokines could be potential biomarkers to predict the occurrence of progressive fibrosis (PF) phenotype among interstitial pneumonia with autoimmune features (IPAF) patients. METHODS: This study prospectively collected 51 IPAF and 15 Idiopathic Pulmonary Fibrosis (IPF) patients who were diagnosed at First Affiliated Hospital of Guangzhou Medical University from July 2020 to June 2021. All IPAF patients were followed up for one year to assess the development of PF phenotype. Paired Broncho Alveolar Lavage Fluid (BALF) and serum samples were collected at enrolment and analyzed for differences in 39 cytokines expression. Principal component analysis (PCA) and cluster analysis were conducted to identify a high-risk subgroup of IPAF patients for developing the PF phenotype. Finally, cytokine differences were compared between subgroups to identify potential biomarkers for PF-IPAF occurrence. RESULTS: According to the PCA analysis, 81.25% of PF-IPAF patients share overlapped BALF cytokine profiles with IPF. Cluster analysis indicated IPAF patients in subtype 2 had a higher risk to develop PF phenotype within one year (P = 0.048), characterized by higher levels of CCL2, CXCL12 and lower lymphocyte proportion (LYM%) in BALF. Elevated levels of BALF CCL2 (>299.16 pg./ml) or CXCL12 (>600.115 pg./ml) were associated with a significantly higher risk of developing PF phenotype within one year follow-up period (P = 0.009, 0.001). CONCLUSION: PF-IPAF phenotype exhibits similar inflammatory cytokine profiles to IPF. Cytokine CCL2, CXCL12, and LYM% in BALF serving as potential biomarkers for predicting the PF phenotype in IPAF patients. CLINICAL TRIAL REGISTRATION: Register: Qian Han, Website: http://www.chictr.org.cn/showproj.aspx?proj=61619, Registration number: ChiCTR2000040998.
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The 5-year recurrence rate of thermal ablation for hepatocellular carcinoma (HCC) is high, and whether this treatment strategy induces systemic immune response remains elusive. This study aimed to investigate the effects of thermal ablation on HCC patients' cytokine profiles and to explore the correlation of cytokine profiles with tumor recurrence after ablation. A total of 22 HCC patients were included in this prospective study. The levels of 27 cytokines in the peripheral blood of HCC patients were measured before ablation (baseline), week 1, and week 4 after ablation using a Bio-Plex Pro Human Cytokine 27-plex Assay kit. Cytokines showed different dynamic changing trends after ablation treatment. It was found that the level of IL-6 was significantly elevated at week 1 and returned to the baseline level at week 4 after ablation. The level of IL-10 was slightly reduced at week 1 and significantly decreased at week 4. The levels of MCP-1, macrophage inflammatory protein-1ß (MIP-1ß), and TNF-α were similarly reduced at week 1 and increased at week 4. The levels of IL-17, platelet-derived growth factor-BB (PDGF-BB), and regulated upon activation, normal T cell expressed and secreted (RANTES) showed little to no change at week 1 while an observable increase at week 4. Patients with a high IL-10 level (2.99 pg/ml) at baseline and low levels of TNF-α (20.4 pg/ml), PDGF-BB (107.78 pg/ml), and RANTES (2303.94 pg/ml) at week 4 were at risk of tumor recurrence during 1-year follow-up. The results suggested that thermal ablation activated systemic immune responses by changing the levels of cytokines. The results also demonstrated that measurement of IL-10 at baseline, TNF-α, PDGF-BB, and RANTES at week 4 after ablation might predict the risk of tumor recurrence.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Interleucina-10 , Neoplasias Hepáticas/patología , Factor de Necrosis Tumoral alfa , Recurrencia Local de Neoplasia , Becaplermina , Estudios Prospectivos , CitocinasRESUMEN
Background: Aspergillus fumigatus-induced chronic pulmonary aspergillosis (CPA), the most common pulmonary tuberculosis (TB) sequela, tends to occur after pulmonary infection with the intracellular pathogen Mycobacterium tuberculosis (Mtb). Timely and accurate detection of A. fumigatus infection of pulmonary TB patients would undoubtedly greatly improve patient prognosis. Currently, the galactomannan (GM) antigen test is commonly used to detect A. fumigatus infection but has poor sensitivity that renders this assay inadequate for use in clinical practice. Design or Methods: Given the fact CPA and TB induce different host immune responses, we evaluated serum cytokine level profiles of CPA, TB patients and patients with both diseases (CPA-TB) for multiple cytokines and cytokine combinations. Results: The results revealed significantly higher serum levels of numerous proinflammatory cytokines, including IL-1ß, IL-6, IL-8, IL-12p70, IFN-α, IFN-γ and TNF-α, in peripheral blood of CPA-TB patients versus that of TB patients. IL-8 levels alone provided the best discriminatory performance for distinguishing between TB and either CPA-TB patients (AUC = 0.949) or CPA patients (AUC = 0.964). Moreover, both IL-8 and TNF-α (AUC = 0.996) levels could be used to distinguish between TB and CPA-TB patients. Likewise, IL-8, TNF-α and IL-6 levels together could be used to distinguish between CPA-TB and TB patients. Conclusion: In this study, multiple cytokines were identified that may serve as potential biomarkers for use in detecting TB patients with CPA. Furthermore, our results should enhance understanding of how immune system dysfunctions influence susceptibility to Mtb and/or A. fumigatus infections.
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We encountered a very rare case of fulminant necrotizing enterocolitis (F-NEC) in a preterm male baby. The course of NEC and sepsis in this case was clearly different from the usual course. After onset at 14 days of life, catheter-related bloodstream infection was first assumed, and antibiotics and γ-globulin administration were started. However, 12 hours after onset, the baby's abdominal distension increased remarkably, and his entire abdominal wall turned red to purple. Escherichia coli were isolated from the blood culture, but the catheter tip culture was negative. Exchange transfusion was performed 32 hours after onset, but no significant changes were observed in the baby's general condition, and he died 46 hours after onset. The acute phase reactants of CRP and α1-acid glycoprotein increased, but haptoglobin did not. Although IL-1ß and TNFα increased as expected with sepsis, IL-6, IL-8, IL-10, and G-CSF however increased to a greater extent than expected. From the above, we diagnosed the development of intestinal necrosis as a result of widespread intestinal ischemia, and that sepsis was associated with this poor condition.
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Enterocolitis Necrotizante , Sepsis , Lactante , Recién Nacido , Masculino , Humanos , Recien Nacido Prematuro , Enterocolitis Necrotizante/diagnóstico , BiomarcadoresRESUMEN
Intravesical bacillus Calmette-Guerin (BCG) instillation is recommended as an adjuvant therapy for intermediate-risk and high-risk non-muscle invasive bladder cancer (NMIBC) after transurethral resection of bladder tumor (TURBt) with nearly 70% reoccurrence. In the present study, we investigated the dynamics of peripheral purified protein derivative (PPD)-specific immune responses along the treatment. Intravesical BCG instillation caused a significant increase in peripheral PPD-specific IFN-γ release of NMIBC patients, when compared to those receiving chemo-drug instillation. Through a follow-up study, we detected rapid increase in PPD-specific IFN-γ, IL-2, and IL-17A producing CD4+ and CD8+ T cells in the induction phase. Interestingly, the frequencies of PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells decreased dramatically after induction treatment and were restored after BCG re-instillation, whereas IL-17A-producing T cells remained at the maintenance phase. However, we only observed that the percentages of peripheral CD8+ T cells were significantly higher in BCG responder patients than those in BCG refractory patients at the baseline with the potential of predicting the recurrence. A more dramatic increase in PPD-specific IFN-γ and IL-2 producing CD4+ and CD8+ T cells after one and two dose BCG instillations was observed in refractory NMIBC patients. Therefore, regional BCG instillation induced transient peripheral PPD-specific T cell responses, which could be restored through repetitive BCG instillation. Higher proportions of peripheral CD8+ T cells at baseline were associated with better responses to BCG instillation for the prevention of recurrence of bladder cancer.
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BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be related to the occurrence of complications, including graft-versus-host disease (GvHD) and infections. The pathogenesis of acute GvHD is connected with T lymphocytes, which identify alloantigens on host's antigen-presenting cells, activate production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), and act on the immune effector cells and damage tissues and organs. AIM: The aim of the study was to investigate and distinguish serum concentration profiles of IFN-gamma and IL-2 within a 30-d period after allo-HSCT. METHODS: We enrolled 62 patients, i.e., 30 (48%) male and 32 (52%) female subjects [median age 49.5 (19-68) years], after allo-HSCT from siblings (n = 12) or unrelated donors (n = 50) due to acute myeloid leukemia with myeloablative conditioning (n = 26; 42%) and with non-myeloablative conditioning (n = 36; 58%). All patients were given standard immunosuppressive therapy with cyclosporin-A and methotrexate and pre-transplant antithymocyte globulin in the unrelated setting. Blood samples were collected pre-transplant before and after (on day -1) the conditioning therapy and on days +2,+4, +6, +10, +20, and +30 after allo-HSCT. Serum levels of IL-2 and IFN-gamma were determined using ELISA. RESULTS: Patients were divided into four groups depending on the presence of acute GvHD and clinical manifestations of infection. Group I included patients with neither acute GvHD nor infections [n = 15 (24%)], group II consisted of patients with infections without acute GvHD [n = 17 (27%)], group III was comprised of patients with acute GvHD without infections [n = 9 (15%)], and group IV included patients with both acute GvHD and infections [n = 21 (34%)]. IFN-gamma concentrations were higher in Group II than in other groups on days +20 (P = 0.014) and +30 (P = 0.008). Post-hoc tests showed lower concentrations of IFN-gamma on day +30 in groups I (P = 0.039) and IV (P = 0.017) compared to group II. The levels of IL-2 were mostly undetectable. CONCLUSION: Serum levels of IFN-gamma following allo-HSCT progressively escalate. High serum levels of IFN-gamma are related to infectious complications rather than acute GvHD. Serum concentrations of IL-2 in most patients are undetectable.
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Background: Cytokines play a vital role in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Here, we investigated the expression of serum cytokine profiles in untreated IIMs and their correlations with clinical indicators, and further studied the expression of related cytokines receptors in IIMs. Methods: The Human 48-Plex Luminex assay for cytokines was performed in the serum of IIMs, including 93 untreated and 18 follow-up (39 samples) patients, and 32 healthy controls (HC). Mann-Whitney U test with bonferroni adjusted was used to identify the differentially expressed cytokines among groups. Celltalker software was used to identify the receptors of differentially expressed cytokines. The expression of receptors was further validated by published GEO datasets (muscle, blood and skin), RT-qPCR, western blot and flow cytometry. Results: The serum levels of Eotaxin, IL7, IL18, IP10, MCP1, MCSF, MIG and SCGFß were elevated in the 93 untreated patients. Except for IL7, all other cytokines were decreased after treatment and their levels were positively correlated with clinical indices such as LDH, ESR, CRP, ALT, IgA, AST and IgG while negatively correlated with albumin and MMT8. According to the serum myositis-specific antibodies (MSAs), patients were classified into three groups: anti-ARS (Jo-1, OJ, EJ, PL7, PL12), anti-MDA5 positive, and anti-TIF1γ positive. Compared with HC, the levels of IP10 and MIG were increased in three groups. Moreover, IL18 and MSCF were increased in anti-ARS patients, and CTACK, Eotaxin, IL1Rα, IL7, IL18, MCP1, MCP3, MCSF and SCGFß were elevated in anti-MDA5 patients. Twenty receptors of the 8 differentially expressed cytokines were matched by celltalker software, among them, IL18R1 and CCR1 were up-regulated in blood, muscle and skin of IIMs from the analysis of GEO published datasets. RT-qPCR and western blot further validated IL18R1 was upregulated in the muscle tissues of dermatomyositis. The number of IL18R1+CD4+ cells was increased while IL18R1+CD8+ cells was decreased in peripheral blood of anti-MDA5 patients. Conclusion: This study showed that cytokine profiles were significantly changed in IIMs, and different MSA groups had unique cytokine expression patterns. The levels of some cytokine were correlated with clinical indices. The IL18 receptor IL18R1 might play important roles in IIMs.
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BACKGROUND: Individuals with relapses of leprosy should be monitored carefully, however, with respect to paucibacillary (PB) leprosy, it is sometimes difficult to make a definitive diagnosis of relapse, because the bacillary index is often negative. To evaluate the usefulness of cytokine profiling in a patient with relapsed PB leprosy who tested negative for anti-phenolic glycolipid-I antibodies, we analyzed the Mycobacterium leprae protein-induced cytokine expression in peripheral blood mononuclear cells of the patient. CASE PRESENTATION: An 89-year-old-male relapsed PB patient, first treated for leprosy over 50 years prior, was examined. In April 2012, he noticed three skin lesions consisting of annular erythema in the thighs. Slit skin smear tests were negative, and skin biopsies revealed a pathology of indeterminate-to-borderline tuberculoid leprosy. He received 600 mg of rifampicin once per month and 75 mg of dapsone daily for 12 months. The annular erythemas disappeared after starting treatment. Before treatment, and 6 and 12 months after starting treatment, the Th1/Th2 cytokine profiles in the supernatant of mononuclear cells from the patient before and after stimulation with Mycobacterium leprae soluble protein (MLS) were examined using a Cytometric Bead Array (CBA) Human Th1/Th2 Cytokine Kit II. The CBA Enhanced Sensitivity Flex Set system was applied to detect small amounts of cytokines in the serum just before treatment and one year before relapse. In the culture supernatant, just before treatment, increases in IFN-γ level and the IFN-γ/IL-10 ratio and a decreased IL-6 level were observed without stimulation. Upon stimulation with MLS, just before treatment, both the IFN-γ and TNF levels increased markedly, and twelve months after starting treatment, the IFN-γ and TNF levels decreased greatly. In the serum, just before treatment, increases in IFN-γ and TNF levels and the IFN-γ/IL-10 ratio were evident compared with those measured one year before relapse. CONCLUSIONS: Cytokine profiling using culture supernatants and serum samples may be useful for the diagnosis of relapsed PB leprosy.
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Lepra Paucibacilar , Lepra , Anciano de 80 o más Años , Citocinas , Humanos , Lepra Paucibacilar/diagnóstico , Lepra Paucibacilar/tratamiento farmacológico , Leucocitos Mononucleares , Masculino , Mycobacterium lepraeRESUMEN
The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore investigated the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays. Among 56 BV-positive women, we observed short-term BV clearance (NS <4) in a proportion of women six weeks after metronidazole treatment, with more than half of these experiencing recurrence by 12 weeks post-treatment. BV treatment temporarily reduced the relative abundance of BV-associated anaerobes (particularly Gardnerella vaginalis and Atopobium vaginae) and increased lactobacilli species (mainly L. iners), resulting in significantly altered mucosal immune milieu over time. In a linear mixed model, the median concentrations of pro-inflammatory cytokines and chemokines were significantly reduced in women who cleared BV compared to pre-treatment. BV persistence and recurrence were strongly associated with mucosal cytokine profiles that may increase the risk of HIV acquisition. Concentrations of these cytokines were differentially regulated by changes in the relative abundance of BVAB1 and G. vaginalis. We conclude that metronidazole for the treatment of BV induced short-term shifts in the vaginal microbiota and mucosal cytokines, while treatment failures promoted persistent elevation of pro-inflammatory cytokine concentrations in the genital tract. These data suggest the need to improve clinical management of BV to minimize BV related reproductive risk factors.
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Antibacterianos/administración & dosificación , Bacterias/efectos de los fármacos , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Metronidazol/administración & dosificación , Membrana Mucosa/efectos de los fármacos , Vagina/efectos de los fármacos , Vaginosis Bacteriana/tratamiento farmacológico , Administración Oral , Adulto , Antibacterianos/efectos adversos , Bacterias/inmunología , Bacterias/patogenicidad , Disbiosis , Femenino , Interacciones Huésped-Patógeno , Humanos , Estudios Longitudinales , Metronidazol/efectos adversos , Membrana Mucosa/inmunología , Membrana Mucosa/metabolismo , Membrana Mucosa/microbiología , Estudios Prospectivos , Reinfección , Sudáfrica , Factores de Tiempo , Resultado del Tratamiento , Vagina/inmunología , Vagina/metabolismo , Vagina/microbiología , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/inmunología , Vaginosis Bacteriana/microbiología , Adulto JovenRESUMEN
SARS-CoV-2 infection in children can trigger cardiovascular manifestations potentially requiring an intensive treatment and defining a new entity named Multisystem Inflammatory Syndrome in Children (MIS-C), whose features partially overlap with Kawasaki Disease (KD). A cross-sectional study including all diagnoses of MIS-C and KD from April 2020 to May 2021 in our metropolitan area was conducted evaluating clinical, laboratory (including immunological response, cytokines, and markers of myocardial damage), and cardiac (coronary and non-coronary) features at onset of the diseases. Evolution of ventricular dysfunction, valve regurgitations, and coronary lesions was documented. The severity of the disease was also considered based on the need for inotropic support and ICU admission. Twenty-four MIS-C were diagnosed (14 boys, median age 82 months): 13/24 cases (54.17%) presented left ventricular dysfunction, 12/24 (50%) required inotropic support, and 10/24 (41.67%) developed coronary anomalies (CALs). All patients received steroids and IVIG at a median time of 5 days (IQR1:4, IQR3:6.5) from onset of fever and heart function normalized 6 days (IQR1: 5, IQR3: 7) after therapy, while CALs persisted in one. One patient (12.5%) required infliximab because of refractory disease and still presented CALs 18 days after therapy. During the same study period, 15 KD were diagnosed: none had ventricular dysfunction, while 7/15 (46.67%) developed CALs. Three out of 15 patients (20%) still presented CALs 46 days from onset. Compared to KD, MIS-C pts have significantly higher IL8 and similar lymphocytes subpopulations. Despite a more severe presentation and initial cardiac findings compared to KD, the myocardial injury in MIS-C has a rapid response to immunomodulatory treatment (median time 6 days), in terms of ventricular function, valve regurgitations, and troponin. Incidence of CALs is similar at onset, but it tends to regress in most of the cases of MIS-C differently than in KD where CALs persist in up to 40% in the subacute stage after treatment.
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COVID-19/complicaciones , COVID-19/patología , Síndrome Mucocutáneo Linfonodular/patología , Miocardio/patología , Síndrome de Respuesta Inflamatoria Sistémica/patología , Disfunción Ventricular Izquierda/patología , Adolescente , COVID-19/diagnóstico , COVID-19/epidemiología , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Interleucina-10/sangre , Interleucina-8/sangre , Italia/epidemiología , Masculino , Síndrome Mucocutáneo Linfonodular/diagnóstico , Estudios Prospectivos , SARS-CoV-2/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Disfunción Ventricular Izquierda/virologíaRESUMEN
We intend to evaluate the differences of the clinical characteristics, cytokine profiles and immunological features in patients with different severity of COVID-19, and to develop novel nomograms based on inflammatory cytokines or lymphocyte subsets for the differential diagnostics for severe or critical and non-severe COVID-19 patients. We retrospectively studied 254 COVID-19 patients, 90 of whom were severe or critical patients and 164 were non-severe patients. Severe or critical patients had significantly higher levels of inflammatory cytokines than non-severe patients as well as lower levels of lymphocyte subsets. Significantly positive correlations between cytokine profiles were observed, while they were all significantly negatively correlated with lymphocyte subsets. Two effective nomograms were developed according to two multivariable logistic regression cox models based on inflammatory cytokine profiles and lymphocyte subsets separately. The areas under the receiver operating characteristics of two nomograms were 0.834 (95% CI: 0.779-0.888) and 0.841 (95% CI: 0.756-0.925). The bootstrapped-concordance indexes of two nomograms were 0.834 and 0.841 in training set, and 0.860 and 0.852 in validation set. Calibration curves and decision curve analyses demonstrated that the nomograms were well calibrated and had significantly more clinical net benefits. Our novel nomograms can accurately predict disease severity of COVID-19, which may facilitate the identification of severe or critical patients and assist physicians in making optimized treatment suggestions.
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COVID-19/diagnóstico , Citocinas/sangre , Técnicas de Apoyo para la Decisión , Mediadores de Inflamación/sangre , Subgrupos Linfocitarios/inmunología , Nomogramas , Anciano , Biomarcadores/sangre , COVID-19/sangre , COVID-19/inmunología , COVID-19/terapia , Toma de Decisiones Clínicas , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Regulación hacia ArribaRESUMEN
BACKGROUND: Postdischarge immunity and its correlation with clinical features among patients recovered from coronavirus disease 2019(COVID-19) are poorly described. This prospective cross-sectional study explored the inflammatory profiles and clinical recovery of patients with COVID-19 at 3 months after hospital discharge. METHODS: Patients with COVID-19 discharged from 4 hospitals in Wuhan, recovered asymptomatic patients (APs) from an isolation hotel, and uninfected healthy controls (HCs) were recruited. Viral nucleic acid and antibody detection, laboratory examination, computed tomography, pulmonary function assessment, multiplex cytokine assay, and flow cytometry were performed. RESULTS: The72 age-, sex- and body mass index-matched participants included 19 patients with severe/critical COVID-19 (SPs), 20 patients with mild/moderate COVID-19 (MPs), 16 APs, and 17 HCs. At 3 months after discharge, levels of proinflammatory cytokines and factors related to vascular injury/repair in patients recovered from COVID-19 had not returned to those of the HCs, especially among recovered SPs compared with recovered MPs and APs. These cytokines were significantly correlated with impaired pulmonary function and chest computed tomographic abnormalities. However, levels of immune cells had returned to nearly normal levels and were not significantly correlated with abnormal clinical features. CONCLUSION: Vascular injury, inflammation, and chemotaxis persisted in patients with COVID-19 and were correlated with abnormal clinical features 3 months after discharge, especially in recovered SPs.
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COVID-19/diagnóstico , COVID-19/inmunología , Citocinas/inmunología , Sobrevivientes/psicología , Cuidados Posteriores , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , COVID-19/epidemiología , COVID-19/terapia , China/epidemiología , Estudios Transversales , Humanos , Alta del Paciente , Estudios Prospectivos , Estudios Retrospectivos , SARS-CoV-2 , Resultado del Tratamiento , Lesiones del Sistema VascularRESUMEN
The aim is to explore the relation between inflammation-associated factors and in-hospital mortality and investigate which factor is an independent predictor of in-hospital death in patients with coronavirus disease-2019. This study included patients with coronavirus disease-2019, who were hospitalized between February 9, 2020, and March 30, 2020. Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO) were used to select variables. Multivariate Cox regression analysis was applied to identify independent risk factors in coronavirus disease-2019. A total of 1135 patients were analyzed during the study period. A total of 35 variables were considered to be risk factors after the univariate regression analysis of the clinical characteristics and laboratory parameters (p < .05), and LASSO regression analysis screened out seven risk factors for further study. The six independent risk factors revealed by multivariate Cox regression were myoglobin (HR, 5.353; 95% CI, 2.633-10.882; p < .001), C-reactive protein (HR, 2.063; 95% CI, 1.036-4.109; p = .039), neutrophil count (HR, 2.015; 95% CI, 1.154-3.518; p = .014), interleukin 6 (Il-6; HR, 9.753; 95% CI, 2.952-32.218; p < .001), age (HR, 2.016; 95% CI, 1.077-3.773; p = .028), and international normalized ratio (HR, 2.595; 95% CI, 1.412-4.769; p = .002). Our results suggested that inflammation-associated factors were significantly associated with in-hospital mortality in coronavirus disease-2019 patients. C-reactive protein, neutrophil count, and interleukin 6 were independent factors for predicting in-hospital mortality and had a better independent predictive ability. We believe these findings may allow early identification of the patients at high risk for death, and can also assist in better management of these patients.
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COVID-19/mortalidad , Hospitalización/estadística & datos numéricos , Inflamación/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/sangre , COVID-19/diagnóstico , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2 , Tasa de SupervivenciaRESUMEN
BACKGROUND: Identifying specific risk factors associated with multiple myeloma (MM) remains a significant issue. Different cytokines take part in the pathogenesis, progression, and prognosis of MM. Therefore, this study aimed to investigate the correlations between serum cytokine levels and clinical characteristics and determine their effects on disease progression and survival of MM patients. METHODS: We retrospectively analyzed the serum levels of 7 cytokines in 105 patients with newly diagnosed MM and in 20 healthy subjects. Interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantitatively determined by cytometric bead assay techniques. The concentrations of each cytokine were compared between the MM patients and healthy subjects using the Mann-Whitney U test. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were higher in patients with newly diagnosed MM than in healthy controls. Positively significant correlations were found between IL-6, IL-10, IL-17A, and ß2-microglobulin. Significant correlations were also observed between IL-6 and IL-10, and lactate dehydrogenase. The overall response rate of low-IL-6 and IL-17A patients was significantly higher than that of high-IL-10 and IL-17A patients (P < 0.01). Univariate and multivariate analyses revealed that serum IL-6 levels were >3 pg/mL, serum IL-17A levels were >4 pg/mL, and treatment regimens were independent prognostic factors for PFS and OS. CONCLUSIONS: Cytokine deregulation, especially that of IL-6 and IL-17A, may be a powerful predictor of clinical prognosis for MM patients.
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Interleucina-17/sangre , Interleucina-6/sangre , Mieloma Múltiple/sangre , Adulto , Anciano , Anciano de 80 o más Años , Citocinas/metabolismo , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Regulación Neoplásica de la Expresión Génica , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Interleucina-2/sangre , Interleucina-4/sangre , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: Low benzene exposure leads to hematotoxicity, but we still lack sensitive early monitoring and early warning markers. Benzene is associated with inflammation, which is mainly mediated by cytokines network. However, until now few studies have conducted high-throughput detection of multi-cytokines to get a global view of cytokine changes and screen for markers of benzene-induced toxicity. We hypothesized that cytokine profiles mediate benzene-induced hematotoxicity. METHODS: 228 subjects consisting of 114 low benzene exposed workers and 114 healthy controls were recruited at Research Center of Occupational Medicine, Peking University Third Hospital, Beijing. The serum concentrations of 27 cytokines were detected by cytokinomics array, urinary benzene series metabolites were measured by UPLC-MS/MS, and peripheral blood cell counts were observed by basic blood test. RESULTS: Among 27 cytokines, IL-9 and MIP1-α were significantly lower, but IL-4, IL-10, IL-15, MCP-1, TNF-α and VEGF were significantly higher in benzene exposure group than controls. Urinary benzene metabolite S-phenylmercapturic acid (S-PMA) was significantly higher in benzene exposure group and had a negative linear relationship with WBC count. S-PMA was only significantly associated with IL-9, meanwhile IL-9, IL-15 and VEGF had a positive linear relationship with WBC count. The bootstrapping mediation models showed that the effect of S-PMA on WBC count was partially explained by IL-9 for 10.11%. CONCLUSION: This study suggests that exposure to benzene was associated with alternation of blood cell count and cytokine profiles in workers exposed to low levels of benzene, especially decreases of WBC count and IL-9. We also found IL-9 partially mediated the effect of low benzene exposure on WBC count, which may be a potential and promising early monitoring and early warning marker of benzene hematotoxicity.
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Contaminantes Ocupacionales del Aire/metabolismo , Benceno/metabolismo , Citocinas/sangre , Exposición Profesional/análisis , Acetilcisteína/análogos & derivados , Adulto , Pueblo Asiatico , Benceno/análisis , Biomarcadores/orina , Recuento de Células Sanguíneas , Cromatografía Liquida , Estudios Transversales , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Exposición Profesional/estadística & datos numéricos , Espectrometría de Masas en TándemRESUMEN
BACKGROUND: Tuberculosis (TB) is an infectious disease and its mortality rate ranks first. Latent tuberculosis infection (LTBI) means that a patient is infected with Mycobacterium tuberculosis, but has no relative clinical symptoms. It has been estimated that approximately 10% of patients with LTBI would develop into active tuberculosis. Therefore, it was urgent to search for more efficient biomarkers to discriminate LTBI from healthy population. METHODS: The Luminex assay was employed to detect the quantity of cytokines secreted by mononuclear cells from peripheral blood stimulated with the ESAT6 protein among TB, LTBI and healthy controls. The cytokine profile was analyzed by principal components analysis and the receiver operating characteristic curve analysis. RESULTS: The principal components analysis indicated that LTBI and TB were clearly separated from healthy controls, and that LTBI was also successfully differentiated from healthy controls. The cytokine profiling method to distinguish LTBI from healthy controls has a sensitivity and specificity of 100%. Nine potential biomarkers, including IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1ß, IL-22 and IL-18, were identified, and these cytokines were considered as a potential cytokine complex for more effectively discriminating LTBI from healthy controls. CONCLUSION: IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1ß, IL-22 and IL-18 were demonstrated to be the potential cytokine complex for the assessment between LTBI and healthy controls.