C‐reactive protein/albumin ratio and IL‐6 are associated with disease activity in patients with ulcerative colitis

BackgroundCytokines are key mediators of the inflammation in ulcerative colitis (UC); there are inconsistent data on cytokines profile in patients with UC. C‐reactive protein/albumin ratio (CRP/ALB) has also been found as an inflammatory indicator. However, the role of CRP/ALB in UC remains unclear. We aimed to evaluate the CRP/ALB ratio and cytokines profile in patients with UC. We further explore the association between CRP/ALB and inflammatory markers, such as erythrocyte sedimentation rate (ESR), fecal calprotectin (FC) and cytokines.MethodsOne hundred thirty UC patients and 65 controls were included in the study. Clinical and laboratory findings were retrospectively reviewed; differences in variables between two groups were examined using the Mann–Whitney U‐test. The association between CRP/ALB, cytokines, and clinical parameters was determined by Spearman''s correlation test.ResultsCRP/ALB levels were significantly elevated in active UC patients. The optimal cutoff level of the CRP/ALB was 0.083. The patients with active UC had a median interleukin‐6 (IL‐6) level of 7.715 pg/ml (interquartile ranges, IQR 3.475–14.63), which was significantly higher than those in remission (2.95 pg/ml, IQR 2.17–5.44) (p < 0.001). Positive correlations between CRP/ALB and inflammatory markers were also observed.ConclusionsOur results suggest that CRP/ALB and IL‐6 could be potential biomarkers for assessment of clinical activity in Chinese patients with UC.     

Serum amyloid a,C‐reactive protein,and procalcitonin levels in children with Mycoplasma pneumoniae infection

Background Mycoplasma pneumoniae (MP) is a common pathogen of community‐acquired pneumonia in children. In the present study, serum amyloid A (SAA), C‐reactive protein (CRP), and procalcitonin (PCT) levels in children with MP infection were analyzed and the differential diagnoses of MP evaluated.MethodsThe study included 152 children with MP infection hospitalized in Tai’an Central Hospital in Shandong Province and 50 healthy children as controls. SAA, CRP, and PCT, as well as serum immunoglobulins and T lymphocyte subsets were analyzed during the acute and convalescent phases. Among the MP‐infected children, 30 cases were selected to monitor the SAA, immunoglobulins, and T lymphocyte subset levels for a week.ResultsThe SAA, CRP, PCT, IgA, and IgM levels were significantly higher in the MP‐infected group than in the control group (F _(SAA) = 83.91, p < 0.05; F _(CRP) = 40.79, p < 0.05; F _(PCT) = 60.58, p < 0.05; F _(IgA) = 43.45, p < 0.05; F _(IgM) = 233.88, p < 0.05). In addition, the levels of these factors were significantly higher in the acute phase than in the convalescent phase (p < 0.05). However, significant difference was not observed in the IgG level between these two groups (p > 0.05). The CD3⁺ and CD4⁺ levels in the MP‐infected group were lower than in the control group ( F _(CD3+)= 60.58, P < 0.05; F _(CD4+) = 89.05, p < 0.05), and the CD8⁺ level was higher than in the control group ( F _(CD8+)= 96.96, p < 0.05). The CD3⁺, CD4⁺, and CD8⁺ levels were significantly different between the acute phase and the convalescent phase (CD3⁺: acute phase vs. convalescent phase, q = 2.79, p < 0.05; CD4⁺: acute phase vs. convalescent phase, q = 2.83, p < 0.05; CD8⁺: acute phase vs. convalescent phase, q = 3.15, p < 0.05). The changes in serum SAA levels in the MP‐infected group positively correlated with the changes in IgA, IgM, and CD8⁺ levels and negatively correlated with CD3⁺, CD4⁺, and CD4⁺/CD8⁺.ConclusionSAA, CRP, and PCT were specific markers for diagnosing early MP infection in children. These findings are important in the differential diagnosis of MP infection and clinical guidance for MP treatment.     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

Th17 cell‐derived miR‐155‐5p modulates interleukin‐17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis

Background miR‐155‐5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)‐17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR‐155‐5p in the regulation of IL‐17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression.MethodsTh17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT‐qPCR and western blotting were used to examine the expression patterns of miR‐155‐5p, IL‐17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR‐155‐5p. RNA pull‐down assays were performed to detect the interaction of IL‐17 and SOCS1 with miR‐155‐5p. In situ hybridization was performed to analyze the co‐expression pattern of miR‐155‐5p and IL17A in Th17 cells.ResultsThe levels of Th17 cell‐derived miR‐155‐5p were significantly up‐regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR‐155‐5p positively regulated IL‐17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR‐155‐5p. The binding status of IL‐17 and SOCS1 to miR‐155‐5p was related to SSc progression. An increase in the co‐localization of miR‐155‐5p and IL‐17 was associated with greater SSc progression.ConclusionsIL‐17 and SOCS1 expression modulated by Th17 cell‐derived miR‐155‐5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.     

Blood Th17 cells and IL‐17A as candidate biomarkers estimating the progression of cognitive impairment in stroke patients

BackgroundT helper (Th) cells regulate immunity and inflammation to engage in cognitive impairment in several neurological diseases, while their clinical relevance in stroke patients is not clear. The current study intended to assess the relationship of Th1 cells, Th17 cells, interferon‐gamma (IFN‐γ), and interleukin (IL)‐17A with cognitive function in stroke patients.MethodsOne hundred twenty stroke patients and 40 controls were enrolled in this muticenter study. Th1 and Th17 cells in peripheral blood were assessed by flow cytometry; meanwhile, IFN‐γ and IL‐17A in serum were detected by enzyme‐linked immunosorbent assay. Cognitive function of stroke patients was evaluated by Mini‐Mental State Examination (MMSE) score at enrollment (baseline), year 1, year 2, and year 3.ResultsTh1 cells (p = 0.037) and IFN‐γ (p = 0.048) were slightly increased, while Th17 cells (p < 0.001) and IL‐17A (p < 0.001) were greatly elevated in stroke patients compared with controls. Th17 cells (r _s = −0.374, p < 0.001) and IL‐17A (r _s = −0.267, p = 0.003) were negatively correlated with MMSE score at baseline, but Th1 cells and IFN‐γ were not. Meanwhile, Th17 cells (p = 0.001) and IL‐17A (p = 0.024) were increased in patients with cognitive impairment compared to those without cognitive impairment. Notably, Th17 cells were positively associated with 1‐year (r _s = 0.331, p < 0.001), 2‐year (r _s = 0.261, p = 0.006), and 3‐year (r _s = 0.256, p = 0.011) MMSE decline; IL‐17A was positively correlated with 1‐year (r _s = 0.262, p = 0.005), 2‐year (r _s = 0.193, p = 0.045), but not 3‐year MMSE decline. However, both Th1 cells and IFN‐γ were not linked with MMSE decline.ConclusionTh17 cells and IL‐17A estimate the progression of cognitive impairment in stroke patients.     

Blood long non‐coding RNA intersectin 1–2 is highly expressed and links with increased Th17 cells,inflammation, multiple organ dysfunction,and mortality risk in sepsis patients

BackgroundLong non‐coding RNA intersectin 1–2 (lnc‐ITSN1‐2) exacerbates inflammation and promotes T‐helper (Th) cell differentiation, also serves as a biomarker in critical illness diseases. However, its clinical role in sepsis remains obscure. Hence, the study aimed to explore the relationship of lnc‐ITSN1‐2 with Th cells, inflammation, disease severity, multiple organ dysfunction, and mortality risk in sepsis.MethodsPeripheral blood mononuclear cells (PBMC) were isolated from 95 sepsis patients and 50 health controls, followed by lnc‐ITSN1‐2 evaluation using RT‐qPCR. PBMC Th1, Th17 cells and their secreted cytokines in serum were detected by flow cytometry and ELISA, respectively.ResultsLnc‐ITSN1‐2 in sepsis patients was higher than it in health controls (Z = −7.328, p < 0.001). Lnc‐ITSN1‐2 correlated with increased interferon‐gamma (p = 0.009), Th17 cells (p = 0.022), and interleukin‐17A (p = 0.006), but not Th1 cells (p = 0.169) in sepsis patients. Moreover, lnc‐ITSN1‐2 had a positive connection with C‐reactive protein (p = 0.001), acute pathologic and chronic health evaluation (APACHE) II (p = 0.024), and sequential organ failure assessment (SOFA) scores (p = 0.022). Regarding SOFA subscales, lnc‐ITSN1‐2 linked with elevated respiratory system score (p = 0.005), cardiovascular system score (p = 0.007), and renal system score (p = 0.004) but no other subscales. Besides, lnc‐ITSN1‐2 had an increasing trend, but no statistical difference, in septic deaths compared to survivors (Z = −1.852, p = 0.064).ConclusionLnc‐ITSN1‐2 reflects sepsis progression and unfavorable prognosis to some extent, which may serve as a potential biomarker to improve the management of sepsis patients.     

Serum IL‐36 cytokines levels in type 2 diabetes mellitus patients and their association with obesity,insulin resistance,and inflammation

BackgroundThe interleukin (IL)‐36 cytokines include IL‐36α, IL‐36β, IL‐36γ, and IL‐36Ra. Little was known about their roles in type 2 diabetes mellitus (T2DM).MethodsThe study included 40 T2DM patients and 42 healthy control subjects. The anthropometric and biochemical measurements were performed using automatic biochemical analyzer, high‐performance liquid chromatography, and electrochemiluminescence immunoassay. Circulating IL‐36α, IL‐36γ, IL‐36Ra, and IL‐17 levels were determined by enzyme‐linked immunosorbent assay.ResultsSerum IL‐36α, IL‐36γ, and IL‐17 levels in T2DM patients were significantly higher than those in controls, whereas serum IL‐36Ra levels in T2DM patients were lower. Correlation analysis showed that serum IL‐36α was positively correlated with high sensitivity C‐reactive protein. Serum IL‐36α was negatively correlated with IL‐36Ra. Serum IL‐17 was negatively correlated with low‐density lipoprotein cholesterol.ConclusionsThis study demonstrated that T2DM patients displayed increased IL‐36α and IL‐36γ expression and decreased IL‐36Ra expression. Moreover, the inflammatory cytokine levels were directly proportional to the inflammation and blood lipid levels. Our results suggest that IL‐36 cytokines may be a new target for the diagnosis or treatment of T2DM.     

Aberrant blood MALT1 and its relevance with multiple organic dysfunctions,T helper cells,inflammation, and mortality risk of sepsis patients

BackgroundMALT1 is linked with multiple organic dysfunctions, inflammatory storm, and T helper (Th) cell differentiation. Herein, the current study aimed to investigate the correlation of peripheral blood mononuclear cell (PBMC) MALT1 with Th1 cells, Th17 cells, and prognosis of sepsis patients.MethodsIn general, 78 sepsis patients and 40 health controls (HCs) were enrolled. MALT1 expression was detected in PBMCs from all subjects by RT‐qPCR. Besides, Th1 and Th17 cells were measured in PBMCs from sepsis patients by flow cytometry; interleukin 17A (IL‐17A) and interferon gamma (IFN‐γ) were determined in serum from sepsis patients by ELISA.ResultsMALT1 expression was higher in sepsis patients than HCs (p < 0.001). MALT1 expression was positively correlated with Th17 cells (r _s = 0.291, p = 0.038) and IL‐17A (r _s = 0.383, p = 0.001), but not with Th1 cells (r _s = 0.204, p = 0.151) or IFN‐γ (r _s = 0.175, p = 0.125) in sepsis patients. MALT1 expression was positively correlated with APACHE II score (r _s = 0.275, p = 0.015), C‐reactive protein (CRP) (r _s = 0.257, p = 0.023), and sequential organ failure assessment (SOFA) score (r _s = 0.306, p = 0.006) (MALT1 expression was positively correlated with SOFA respiratory system score (r _s = 0.348, p = 0.002), and SOFA liver score (r _s = 0.260, p = 0.021), but not with SOFA scores in nervous system, cardio vascular system, coagulation, and renal system (all p > 0.05)). MALT1 expression (p = 0.010), Th1 cells (p = 0.010), Th17 cells (p = 0.038), and IL‐17A (p = 0.012), except for IFN‐γ (p = 0.102), elevated in sepsis deaths compared with sepsis survivors.ConclusionPBMC MALT1 is highly expressed in sepsis patients with its overexpression associated with multiple organic dysfunctions, elevated Th17 cells, and increased mortality risk.     

Potential of long non‐coding RNA KCNQ1OT1 as a biomarker reflecting systemic inflammation,multiple organ dysfunction,and mortality risk in sepsis patients

BackgroundLong non‐coding RNA potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (lnc‐KCNQ1OT1) represses inflammation and multiple organ dysfunction, whereas its clinical value in sepsis is unclear. Thus, this study aimed to explore this issue.MethodsLnc‐KCNQ1OT1 from peripheral blood mononuclear cells were detected by RT‐qPCR in 116 sepsis patients and 60 healthy controls (HCs). Moreover, sepsis patients were followed‐up until death or up to 28 days.ResultsLnc‐KCNQ1OT1 decreased in patients with sepsis than in HCs (p < 0.001). In sepsis patients, lnc‐KCNQ1OT1 was negatively correlated with sequential organ failure assessment (SOFA) scores (r = −0.344, p < 0.001) and several SOFA subscale scores (including respiratory system, coagulation, liver, and renal systems) (all r < 0, p < 0.05). Furthermore, lnc‐KCNQ1OT1 was negatively correlated with CRP (r = −0.386, p < 0.001), TNF‐α (r = −0.332, p < 0.001), IL‐1β (r = −0.319, p < 0.001), and IL‐6 (r = −0.255, p = 0.006). Additionally, lnc‐KCNQ1OT1 levels were lower in sepsis deaths than in sepsis survivors (p < 0.001), and the receiver operating characteristic curve showed that lnc‐KCNQ1OT1 had an acceptable ability to predict 28‐day mortality (area under the curve: 0.780, 95% confidence interval: 0.678–0.882). Meanwhile, its ability to predict 28‐day mortality risk was higher than that of CRP, TNF‐α, IL‐1β, and IL‐6, but slightly lower than the SOFA score and acute physiology and chronic health evaluation II score.ConclusionLnc‐KCNQ1OT1 serves as a potential biomarker for monitoring disease severity and prognosis in patients with sepsis.