scholarly journals 1731. Immune Dysregulation in Mucormycosis

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S634-S634
Author(s):  
Chhavi Gupta ◽  
Shukla Das ◽  
Gargi Rai ◽  
Praveen K Singh ◽  
Sajad Dar ◽  
...  
Keyword(s):  
T Cell ◽  
Fungal Infection ◽  
Therapeutic Option ◽  
Immune Dysregulation ◽  
Diabetic Patients ◽  
Becton Dickinson ◽  
Chronic Inflammatory Response ◽  
Cell Parameters ◽  
Immune Parameters ◽  
Healthy Control

Abstract Background Mucormycosis is a fatal fungal infection with unique predisposition to infect diabetics. Dysregulated adaptive immunity contributes to the pathogenesis in all fungal diseases, but activated Th17 cells have laid a new dimension to chronic inflammatory response which was previously attributed to uncontrolled Th1 response. We attempted to study the Th17 and T regulatory (Treg) immune response in diabetic patients with mucormycosis and compared the data with a healthy control and a T2DM case without fungal infection. In addition we could follow-up one patient post 6-month treatment and performed immunological studies. Methods 2 mL of blood samples were collected in EDTA vial from two patients who were suffering from diabetes with mucormycosis for immunological investigations. Samples were also taken from age-matched T2DM patient without fungal infection and a healthy volunteer as controls for T-cell parameters. Repeat blood sample was taken to study immune parameters in one patient who was followed up after 6 months. The expression of various T-cell markers was analyzed by immunostaining with the antibodies against CD3, CD4, CD25, CD161, IL-23R [Becton Dickinson (BD) PharMingen]. Fluorescence profiles were analyzed using Flow Jo software (BD Biosciences). The results are expressed as a percentage of positive cells. Results The percentages of CD4+ cells were low in both patients when compared with and healthy control but it is much higher in diabetes case when compared with others. CD161+ cell population was higher in both patients when compared with healthy control and diabetic patient without fungal infection. The percentage of IL23R+ cells was significantly high in patient before treatment when compared with, healthy control and diabetics. and decline after treatment. The percentage positivity of CD25+ cells was highest in healthy control when compared with others. The profile of CD25+ cells was comparatively similar in patient before treatment and diabetics but we found a higher percentage, in patients after treatment. Conclusion The findings in this study imminently indicate the mechanism of immune dysregulation involving Th17 and Treg pathways in mucormycosis and provide evidence that restoration of Th17/Treg may be considered as a therapeutic option for long-term benefit in diabetics. Disclosures All authors: No reported disclosures.

scholarly journals Risk of Typical Diabetes-Associated Complications in Different Clusters of Diabetic Patients: Analysis of Nine Risk Factors

2021 ◽  
Vol 11 (5) ◽  
pp. 328
Author(s):  
Michael Leutner ◽  
Nils Haug ◽  
Luise Bellach ◽  
Elma Dervic ◽  
Alexander Kautzky ◽  
...  
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Diabetic Patients ◽  
Complication Risk ◽  
Increased Risk ◽  
Icd 10 ◽  
Healthy Control ◽  
Design And Methods ◽  
The Relationship ◽  
Observation Period

Objectives: Diabetic patients are often diagnosed with several comorbidities. The aim of the present study was to investigate the relationship between different combinations of risk factors and complications in diabetic patients. Research design and methods: We used a longitudinal, population-wide dataset of patients with hospital diagnoses and identified all patients (n = 195,575) receiving a diagnosis of diabetes in the observation period from 2003–2014. We defined nine ICD-10-codes as risk factors and 16 ICD-10 codes as complications. Using a computational algorithm, cohort patients were assigned to clusters based on the risk factors they were diagnosed with. The clusters were defined so that the patients assigned to them developed similar complications. Complication risk was quantified in terms of relative risk (RR) compared with healthy control patients. Results: We identified five clusters associated with an increased risk of complications. A combined diagnosis of arterial hypertension (aHTN) and dyslipidemia was shared by all clusters and expressed a baseline of increased risk. Additional diagnosis of (1) smoking, (2) depression, (3) liver disease, or (4) obesity made up the other four clusters and further increased the risk of complications. Cluster 9 (aHTN, dyslipidemia and depression) represented diabetic patients at high risk of angina pectoris “AP” (RR: 7.35, CI: 6.74–8.01), kidney disease (RR: 3.18, CI: 3.04–3.32), polyneuropathy (RR: 4.80, CI: 4.23–5.45), and stroke (RR: 4.32, CI: 3.95–4.71), whereas cluster 10 (aHTN, dyslipidemia and smoking) identified patients with the highest risk of AP (RR: 10.10, CI: 9.28–10.98), atherosclerosis (RR: 4.07, CI: 3.84–4.31), and loss of extremities (RR: 4.21, CI: 1.5–11.84) compared to the controls. Conclusions: A comorbidity of aHTN and dyslipidemia was shown to be associated with diabetic complications across all risk-clusters. This effect was amplified by a combination with either depression, smoking, obesity, or non-specific liver disease.

N-3 Polyunsaturated Fatty Acids Modulate In-Vitro T Cell Function in Type I Diabetic Patients

Lipids ◽  
2008 ◽  
Vol 43 (6) ◽  
pp. 485-497 ◽  
Author(s):  
Sid Ahmed Merzouk ◽  
Meriem Saker ◽  
Karima Briksi Reguig ◽  
Nassima Soulimane ◽  
Hafida Merzouk ◽  
...  
Keyword(s):  
Fatty Acids ◽  
T Cell ◽  
Polyunsaturated Fatty Acids ◽  
Cell Function ◽  
Diabetic Patients ◽  
Type I ◽  
T Cell Function

#78: Use of Isavuconazonium for Treatment Of Invasive Fungal Infection in Immunocompromised Pediatric Patients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S2-S2
Author(s):  
Sindhu Mohandas ◽  
Kanokporn Mongkolrattanothai ◽  
Leslie Stach ◽  
Regina Orbach ◽  
Michael Neely
Keyword(s):  
Fungal Infection ◽  
Invasive Fungal Infection ◽  
Liposomal Amphotericin ◽  
Fungal Pathogens ◽  
Pediatric Patients ◽  
Therapeutic Option ◽  
Dual Therapy ◽  
Primary Diagnosis ◽  
Cardiac Transplant ◽  
Serum Concentrations

Abstract Background Isavuconazole (ISZ), dosed as the pre-drug isavuconazonium (ISM), is active against a wide variety of clinically important fungal pathogens. ISM is approved for the treatment of invasive aspergillosis and mucormycosis in adults ≥18 years of age. We present our experience with ISM to treat proven or probable fungal infection in immunocompromised pediatric patients. Methods Retrospective review of patients who received ISM at our institution between April 2016 and April 2019, we abstracted demographic information, primary diagnosis, indication for ISM therapy, ISZ serum concentrations if available, and outcomes. Results Of 14 patients who received ISM, 11 were ≤18 years of age (range 6–18 years). Underlying conditions included leukemia (n = 7), lymphoma (n = 1), post BMT (n = 1), diabetes (n = 1), and cardiac transplant (n = 1). Nine (82%) had proven invasive fungal infection (IFI) with aspergillosis (n = 2), zygomycosis (n = 3), mixed aspergillosis and zygomycosis (n = 2), mixed Rhizopus and Scedosporium (n = 1), and pathology only (n = 1) and 2 had probable IFI. Five of these 11 patients received combination ISM and liposomal amphotericin initially and the other 6 received liposomal amphotericin with or without other azoles prior to changing to ISM monotherapy. This was followed by monotherapy with ISM in 10 patients after a mean of 26 days (range 6–63) and continued dual therapy in the one. ISM dosing was 10 mg/kg q8h on days 1 and 2, followed by q24 thereafter, up to a maximum of 372 mg/dose. There were 19 measured ISZ serum concentrations obtained from 8 patients after >1 week of verified inpatient dosing, ranging from 1.0 to 7.5 mg/L, above the MIC in all cases when known. Three (27%) patients died of underlying non-mycological causes, 1 (9%) died of progressive scedosporiosis, and 7 (64%) improved. ISM was well tolerated with no dose-limiting, drug-related toxicities noted. Conclusions ISM is a well-tolerated therapeutic option in pediatric patients at risk for or with invasive mycosis. Only 1 of our 11 patients died from progressive fungal disease.

scholarly journals Effect of 3 Months of Doxazosin Therapy on T-Cell Subsets in Type 2 Diabetic Patients

2009 ◽  
Vol 37 (6) ◽  
pp. 1982-1987 ◽  
Author(s):  
E Mácsai ◽  
Á Cseh ◽  
G Budai ◽  
G Mészáros ◽  
B Vásárhelyi ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Subsets ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic

Immunomodulations induced in rats by exercise on a treadmill

1990 ◽  
Vol 69 (5) ◽  
pp. 1912-1915 ◽  
Author(s):  
A. Ferry ◽  
B. L. Weill ◽  
M. Rieu
Keyword(s):  
T Cell ◽  
Treadmill Exercise ◽  
Absolute Number ◽  
Not Given ◽  
Spleen Cells ◽  
Immune Parameters ◽  
Exercise Regimen ◽  
Long Duration

Various regimens of treadmill exercise (0% slope) were used with rats: 60 min at 15 m/min (T-15), 180 min at 10 m/min (T-10), and 60 min/day at 15 m/min for 6 consecutive days (T-15-6). Exercise resulted in 1) decreases in the absolute number of mononuclear spleen cells in T-10 rats, 2) significant increases in in vitro splenic T-cell blastogenesis in response to phytohemagglutinin in T-10 rats, and 3) significant decreases in T-cell blastogenesis in T-15-6 rats. T-15-6 rats were given aminoglutethimide per os before exercise sessions to study the role of corticosteroids in the alteration of splenic T-cell blastogenesis. Aminoglutethimide significantly increased the T-cell blastogenesis in these T-15-6 rats compared with those not given aminoglutethimide, whereas it had no effect on immune parameters of sedentary rats. These results show that immunomodulations in the rat depend on the treadmill exercise regimen employed. If the mechanisms of the immunomodulation induced by isolated exercise of long duration are not elucidated, these data suggest that corticosteroids are involved in the alteration in T-cell blastogenesis induced by chronic muscular exercise.

scholarly journals T-cell mediated autoimmunity to the insulinoma-associated protein 2 islet tyrosine phosphatase in type 1 diabetes mellitus

1999 ◽  
pp. 272-278 ◽  
Author(s):  
F Dotta ◽  
S Dionisi ◽  
V Viglietta ◽  
C Tiberti ◽  
MC Matteoli ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Type 1 Diabetes ◽  
T Cell ◽  
T Lymphocyte ◽  
Tyrosine Phosphatase ◽  
T Cell Response ◽  
T Cell Proliferation ◽  
Diabetic Patients ◽  
Hla Dr

The target molecules of the T-cell response in type 1 diabetes, despite their pathogenic importance, remain largely uncharacterized, especially in humans. Interestingly, molecules such as insulin and glutamic acid decarboxylase (GAD) have been shown to be a target not only of autoantibodies, but also of autoreactive T-lymphocytes both in man and in the non-obese diabetic (NOD) mouse. In the present study we aimed to determine the existence of a specific T-cell response towards the insulinoma-associated protein 2 (IA-2) islet tyrosine phosphatase, a recently identified autoantigen which is the target of autoantibodies strongly associated with diabetes development. Human recombinant IA-2 produced in Escherichia coli, was tested for its reactivity with peripheral blood lymphocytes obtained from 16 newly diagnosed type 1 diabetic patients and from 25 normal controls, 15 of whom were HLA-DR-matched. A T-cell proliferation assay was performed in triplicate employing freshly isolated cells in the absence or in the presence of the antigen to be tested (at two different concentrations: 2 microg/ml and 10 microg/ml). A specific T-cell proliferation (defined as a stimulation index (S.I.) >/=3) was observed against IA-2 used at a concentration of 10 microg/ml (but not of 2 microg/ml) in 8/16 diabetic patients, in 1/15 HLA-DR-matched control subjects (P<0.01 by Fisher exact test) and in 0/10 of the remaining normal individuals. A statistically significant difference (P<0.003 by Mann-Whitney U test) was also observed in S.I. values between patients (3.1+/-1.4) and HLA-DR-matched controls (1.7+/-0.54) employing IA-2 at a concentration of 10 microg/ml. However, when IA-2 was used at a concentration of 2 microg/ml, the difference in S. I. between patients (1.65+/-0.8) and controls (1.0+/-0.3) did not reach statistical significance. In conclusion, these data show the presence of a specific, dose-dependent T-lymphocyte response against the IA-2 islet tyrosine phosphatase at the onset of type 1 diabetes. Consequently, this molecule appears to be a target not only at the B-lymphocyte but also at the T-lymphocyte level, reinforcing the potential pathogenic role of this autoantigen in the islet destructive process.

scholarly journals Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

2020 ◽  
Vol 20 (2) ◽  
pp. 833-840
Author(s):  
Erhan Onalan ◽  
Yusuf Doğan ◽  
Ebru Onalan ◽  
Nevzat Gozel ◽  
Ilay Buran ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
High Serum ◽  
Control Group ◽  
Diabetic Patients ◽  
Healthy Individuals ◽  
Urine Albumin ◽  
Healthy Control ◽  
Group 2

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

scholarly journals IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3101
Author(s):  
Cuiping Zhang ◽  
Mina Delawary ◽  
Peng Huang ◽  
Jennifer A. Korchak ◽  
Koji Suda ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Therapeutic Potential ◽  
Immune Dysregulation ◽  
T Cell Proliferation ◽  
Immunomodulatory Effects ◽  
Freezing And Thawing ◽  
Mrna Transfection ◽  
Clinical Conditions

Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited efficacy. Various methods have been assessed to increase the potency of MSCs. IL-10 is an anti-inflammatory cytokine that is known to modulate immune responses in GvHD. In this study, we evaluated the feasibility of transfecting IL-10 mRNA to enhance MSC therapeutic potential. IL-10 mRNA engineered MSCs (eMSCs-IL10) maintained high levels of IL-10 expression even after freezing and thawing. IL-10 mRNA transfection did not appear to alter MSC intrinsic characteristics. eMSCs-IL10 significantly suppressed T cell proliferation relative to naïve MSCs in vitro. In a mouse model for GvHD, eMSCs-IL10 induced a decrease in plasma level of potent pro-inflammatory cytokines and inhibited CD4+ and CD8+ T cell proliferation in the spleen. In summary, our studies demonstrate the feasibility of potentiating MSCs to enhance their immunomodulatory effects by IL-10 mRNA transfection. The use of non-viral transfection may generate a safe and potent MSC product for treatment of clinical conditions associated with immune dysregulation such as GvHD.

scholarly journals Correlation between Level of Autophagy and Amount of CD8+T Cells in Chronic Obstructive Pulmonary Disease

2020 ◽  
Author(s):  
Songming Zhuo ◽  
Hong Zhuang ◽  
Na Li ◽  
Sida Chen ◽  
Wugen Zhan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lung Function ◽  
Normal Lung ◽  
Stable Phase ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Normal Lung Function ◽  
Healthy Control ◽  
Function Group

Abstract Background: This study aimed to shed light on the correlation between the amounts of CD8+ T cells and autophagy level in COPD. Results: The objects (n = 90) were divided into three groups: COPD group (patients in the stable phase; n = 30), SN group (healthy control of smoking with normal lung function group; n = 30), and NSN groups (healthy control of non-smoking with normal lung function group; n = 30). The amounts of CD8+ (32.33 ± 4.23%), CD8+ effector (25.63 ± 8.57%) and CD8+memory (11.94 ± 5.77%) T cell in the COPD group were significantly higher those in the other two groups, while the apoptotic rate was lower in the COPD group (P < 0.05). Significant linear correlations were found of P62/GAPDH (‰) with CD8+, CD8+effector, and CD8+ memory- T cell amounts (P<0.001). Conclusions: Autophagy level is positively and linearly associated with the amounts of CD8+ T cells, suggesting that cell autophagy might be involved in COPD pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document