Serum complement C4b, fibronectin, and prolidase are associated with the pathological changes of pulmonary tuberculosis.
ABSTRACT: BACKGROUND: Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation. METHODS: Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups. RESULTS: We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05). CONCLUSIONS: Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB.
Project description:Triggering receptor expressed on myeloid cells 1 (TREM-1) amplifies inflammatory responses and is upregulated during sepsis and pulmonary infection. The association between serum soluble TREM-1 (sTREM-1) level and pulmonary tuberculosis (PTB) disease deserves investigation. In the present study, patients with PTB, latent TB infection (LTBI), and non-TB, non-LTBI subjects were prospectively enrolled and serum levels of sTREM-1, sTREM-2, and C-reactive protein (CRP) were measured. We correlated serum biomarkers and clinical presentations and treatment outcomes of PTB cases. We also utilized immunohistochemistry (IHC) to visualize TREM-1-expressing cells in lung tissues from PTB patients. A total of 86 PTB, 41 LTBI, and 20 non-TB, non-LTBI subjects were enrolled. Serum levels of sTREM-1 and CRP significantly increased in PTB patients; these higher serum levels were correlated with more advanced involvement in chest films and higher bacteria burden in sputum. In multivariate analysis, serum levels of sTREM-1 >260?pg/mL and CRP >2.6?mg/L were independent predictors for on-treatment mortality. Abundant TREM-1-expressing macrophages were identified in lung tissues from PTB samples. In conclusion, serum levels of sTREM-1 correlated with disease severity and treatment outcomes in PTB patients.
Project description:BACKGROUND:Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. METHODS:We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-?; and C-reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement. RESULTS:After correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 ?g/dL) and vitamin E (?-tocopherol [8.7 vs 10.3 mg/L] and ?-tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both ?-tocopherol and ?-tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP. CONCLUSIONS:CP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.
Project description:Tuberculosis (TB) remains a leading cause of fatal infectious disease. Accumulations of macrophages are found in infected sites; thus, we hypothesized that a marker of activated macrophages may be related to prognosis of pulmonary TB (PTB). This study investigated serum soluble macrophage mannose receptor, sCD206, in PTB and examined its clinical significance. First, the concentration of sCD206 was measured in the sera of 96 patients with PTB (Tenryu cohort), and in pleural effusions from 29 patients with TB pleurisy. These were verified in another independent cohort (Shizuoka cohort). We found increased concentrations of sCD206 in sera, but not in pleural effusions of PTB patients. Notably, PTB patients with poor prognosis showed significantly higher levels of serum sCD206. At a cut-off value of 1,600?ng/mL in the Tenryu cohort, sCD206 predicted prognosis of PTB with area under the curve 0.847, sensitivity 77.3%, and specificity 86.5%. These results were validated in the Shizuoka cohort. Pathological analyses showed concordance of enhanced CD206 expression in lung and pleural tissues with caseating granuloma in TB. Serum sCD206 increased in PTB and was associated with prognosis. sCD206 is a potential biomarker for PTB.
Project description:Mycobacterium tuberculosis remains a significant global health concern largely due to its ability to persist for extended periods within the granuloma of the host. While residing within the granuloma, the tubercle bacilli are likely to be exposed to stress that can result in formation of aberrant proteins with altered structures. Bacteria encode stress responsive determinants such as proteases and chaperones to deal with misfolded or unfolded proteins. pepD encodes an HtrA-like serine protease and is thought to process proteins altered following exposure of M. tuberculosis to extra-cytoplasmic stress. PepD functions both as a protease and chaperone in vitro, and is required for aspects of M. tuberculosis virulence in vivo. pepD is directly regulated by the stress-responsive two-component signal transduction system MprAB and indirectly by extracytoplasmic function (ECF) sigma factor SigE. Loss of PepD also impacts expression of other stress-responsive determinants in M. tuberculosis. To further understand the role of PepD in stress adaptation by M. tuberculosis, a proteomics approach was taken to identify binding proteins and possible substrates of this protein. Using subcellular fractionation, the cellular localization of wild-type and PepD variants was determined. Purified fractions as well as whole cell lysates from Mycobacterium smegmatis or M. tuberculosis strains expressing a catalytically compromised PepD variant were immunoprecipitated for PepD and subjected to LC-MS/MS analyses. Using this strategy, the 35-kDa antigen encoding a homolog of the PspA phage shock protein was identified as a predominant binding partner and substrate of PepD. We postulate that proteolytic cleavage of the 35-kDa antigen by PepD helps maintain cell wall homeostasis in Mycobacterium and regulates specific stress response pathways during periods of extracytoplasmic stress.
Project description:We investigated whether high-protein enteral nutrition with immune-modulating nutrients (IMHP) enriched with ?-glucan stimulates immune function in critically ill patients. In a randomized double-blind placebo-controlled study, 30 patients consumed one of three types of enteral nutrition: a control or IMHP with and without ?-glucan. The IMHP with ?-glucan group showed increases in natural killer (NK) cell activities relative to the baseline, and greater increases were observed in NK cell activities relative to the control group after adjusting for age and gender. The IMHP groups with and without ?-glucan had greater increases in serum prealbumin and decreases in high-sensitivity C-reactive protein (hs-CRP) than the control group. The control group had a greater decrease in peripheral blood mononuclear cell (PBMC) interleukin (IL)-12 production than the IMHP with and without ?-glucan groups. In all patients, the change (?) in hs-CRP was correlated with ? prealbumin and ? PBMC IL-12, which were correlated with ?NK cell activity and ? prealbumin. This study showed beneficial effects of a combination treatment of ?-glucan and IMHP on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12, and hs-CRP suggested that ?-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation (ClinicalTrials.gov: NCT02569203).
Project description:BACKGROUND:Pulmonary tuberculosis (PTB) is characterized by elevated levels of acute phase proteins (APPs), but their association with tuberculous lymphadenitis (TBL) is poorly studied. METHODS:We examined the systemic levels of APPs (alpha-2-macroglobulin [?-2MG], serum amyloid A [SAA], C-reactive protein [CRP] and haptoglobin [Hp]) in TBL, PTB, latent tuberculosis (LTB) and healthy controls (HC) at baseline and in TBL after the completion of anti-tuberculosis treatment (ATT). We have also examined the association of these proteins with lymph node (LN) size, culture grade and multiple versus single LN involvement. RESULTS:TBL individuals exhibited increased systemic levels of ?-2MG, SAA, CRP and Hp in comparison to HCs and increased CRP levels in comparison to LTB individuals. TBL individuals also exhibited decreased systemic levels of Hp compared to PTB individuals. APPs were not significantly associated with LN size, LN involvement and culture grade, indicating a lack of association with disease severity. Following ATT, post-treatment levels of ?-2MG, CRP and Hp were significantly diminished compared to pre-treatment levels. CONCLUSION:TBL disease is characterized by altered levels of APPs at baseline and modulated following treatment, indicating the presence of systemic inflammation.
Project description:<h4>Purpose</h4>Feeding children is a problem in pediatric intensive care units (PICU) and it is difficult to know the correct amount. The purpose of this study is to evaluate if prealbumin or retinol binding proteins (RBP) are effective relative to daily enteral nutrition, without being affected by severity of diseases or infections and can be used to follow up nutritional amount.<h4>Methods</h4>This is a prospective observational study that includes 81 patients admitted to PICU in Akdeniz University with estimated duration >72 hours, age between 1 month and 8 years. Daily calorie and protein intake were calculated and prealbumin, RBP and C-reactive protein (CRP) levels were measured on the first, third, fifth and seventh mornings.<h4>Results</h4>We find moderate correlation between daily calorie intake and prealbumin levels (r=0.432, <i>p</i><0.001), RBP levels and daily protein intake (r=0.330, <i>p</i><0.001). When we investigated the relationship between changes of prealbumin, RBP, CRP, calorie and protein intake during intensive care stay, we found that increase of Prealbumin and RBP levels are explained by decrease of CRP levels (r=-0.546 and -0.645, <i>p</i><0.001) and not with increase of nourishment.<h4>Conclusion</h4>Even adjusted for PRISM3, age and CRP, prealbumin and RBP are correlated with last 24 hours' diet. However, it is not convenient to use as a follow up biomarker because increase of their levels is related with decrease of CRP levels.
Project description:OBJECTIVE:To evaluate C-reactive protein (CRP), globulin and white blood cell (WBC) count as predictors of treatment outcome in pulmonary tuberculosis (PTB). METHODS:An observational study of patients with active PTB was conducted at a tertiary centre. All patients had serum CRP, globulin and WBC measured at baseline and at 2 months following commencement of treatment. The outcome of interest was requirement for extension of treatment beyond 6 months. RESULTS:There were 226 patients included in the study. Serum globulin 45 g/l was the only baseline biomarker evaluated that independently predicted requirement for treatment extension (OR 3.42, 95%CI 1.597.32, P 0.001). An elevated globulin level that failed to normalise at 2 months was also associated with increased requirement for treatment extension (63.9% vs. 5.1%, P 0.001), and had a low negative likelihood ratio (0.07) for exclusion of requirement for treatment extension. On multivariable analysis, an elevated globulin that failed to normalise at 2 months was independently associated with requirement for treatment extension (OR 6.13, 95%CI 2.2316.80, P 0.001). CONCLUSIONS:Serum globulin independently predicts requirement for treatment extension in PTB and outperforms CRP and WBC as a predictive biomarker. Normalisation of globulin at 2 months following treatment commencement is associated with low risk of requirement for treatment extension.
Project description:End-stage renal disease (ESRD) patients are vulnerable to vitamin D deficiency due to impaired renal hydroxylation, low dietary intake and inadequate sun exposure. Vitamin D plays a role in innate and adaptive immunity and its seasonal variation has been linked to mortality. ESRD is associated with inadequate removal of pro-inflammatory cytokines regulating acute phase protein (APP) synthesis. Our aim was to look for associations between lifestyle factors, diet, and vitamin D seasonal variation and their relationship with selected APPs and calcium-phosphate metabolism. The study included 59 ESRD patients treated with maintenance hemodialysis. A 24-hour dietary recall was conducted in the post-summer (November 2018, PS) and post-winter (February/March 2019, PW) period, and blood was collected for the measurements of serum total vitamin D, ?1-acid glycoprotein (AGP), C-reactive protein (CRP), albumin, prealbumin (PRE), parathormone, calcium and phosphate. A self-constructed questionnaire gathered information on vitamin D supplementation, sun exposure and physical activity. Higher caloric intake was observed PW compared PS. Less than 15% of participants met the dietary recommendations for energy, protein, fiber, vitamin D and magnesium intake. Vitamin D supplementation was associated with higher serum vitamin D regardless of season. AGP, PRE, albumin, and vitamin D presented seasonal changes (higher values PS). In patients with serum vitamin D below 25 ng/mL, vitamin D seasonal change correlated with CRP and prealbumin change. Phosphate and Ca × P correlated positively with AGP. A low vitamin D serum level could impact the inflammatory process; however, more studies are needed to confirm the relationship.
Project description:Hyperglycemia and protein loss are common in critically ill patients. Insulin can be used to lower blood glucose and inhibit proteolysis. The impact of moderate insulin therapy on protein metabolism in critically ill patients has not been evaluated. We compared urinary nitrogen excretion, nitrogen balance, serum albumin concentrations, prealbumin concentrations, and clinical outcomes between patients receiving moderate insulin therapy (MIT) and conventional insulin therapy (CIT) in a medical ICU.Patients were randomly divided into groups and treated with MIT (glucose target 120 to 140 mg/dl) or CIT (glucose target 180 to 200 mg/dl). Calories and protein intake were recorded each day. On days 3, 7 and 14, the 24-hour urinary nitrogen excretion, nitrogen balance, and serum albumin and prealbumin concentrations were measured. Clinical outcomes data were collected.A total of 112 medical ICU patients were included, with 55 patients randomized to the MIT group and 57 patients randomized to the CIT group. Patients treated with MIT showed a trend towards increased nitrogen balance (P = 0.070), significantly lower urinary nitrogen excretion (P = 0.027), and higher serum albumin (P = 0.047) and prealbumin (P = 0.001) concentrations than patients treated with CIT. The differences between the two groups were most significant on day 3, when all factors showed significant differences (P < 0.05).Moderate glucose control results in less negative nitrogen balances in medical ICU patients. Differences are more significant in the early stages compared with the late stages of critical illness.ClinicalTrial.Gov NCT 01227148.