Gut-microbiota alterations and bacterial translocation might attribute to hepatic inflammation. Lipopolysaccharide stimulates toll-like receptor 4 leading to the activation of Kupffer cells which ...express the surface receptor, CD 163.
To assess the levels of CD 163 and LPS in overweight and obese patients with different degrees of NAFLD as confirmed by liver biopsy (NAS score).
This is an observational case-control study. Sixty overweight and obese patients with NAFLD and 40 healthy controls were enrolled in the study. Liver biopsy was obtained from all participants with NAFLD. LPS and CD 163 levels were assessed using ELISA.
The mean LPS and CD163 levels were significantly higher in patients with NAFLD when compared with healthy controls (p-value <0.001, p-value <0.001, respectively). LPS and CD163 levels were the lowest in Non-NASH (13.17 ± 3.34, 5.61 ± 2.35 ng/mL, respectively) and the highest in NASH (58.61 3± 3.81, 18.11 ± 6.84, respectively) (p-value <0.001, p-value <0.001, respectively). Statistically significant correlation was found between the levels of LPS and CD163 and NAS score (p-value <0.001, p-value < 0.001, respectively), steatosis grade (p-value <0.001, p-value <0.001, respectively), degree of inflammation (p-value 0.017, p-value <0.001, respectively) and ballooning (r= 0.663, p-value <0.001, r= 0.558, p-value <0.001, respectively). In ROC analysis, both sCD163 and LPS had high sensitivity and specificity in diagnosing NAFLD. CD163 and LPS had the high sensitivity and accuracy in discriminating NASH from Non-NASH (p-value <0.0001 in both). Moreover, the mean serum levels of LPS and sCD163 correlated positively and significantly with the BMI (r=0.329, p value<0.01; r=0.477. p value <0.001, respectively).
sCD163 and LPS can be used as non-invasive tools for diagnosis and grading of NAFLD severity in overweight and obese patients, thus confirming the role of dysbiosis in fat deposition and inflammation and suggesting the potential benefits of gut-microbiota-targeted therapies in restoring the gut homeostasis.
Objectives
Autophagy is a complex cellular process that maintains homeostasis in systemic lupus erythematosus. Abnormally high expression of Bcl-2 was observed in B and T lymphocytes in the ...peripheral blood in SLE patients. These may be responsible for the survival of self-reactive lymphocytes and the development of lupus, and the study aims at evaluating interaction between apoptosis and autophagy in Egyptian lupus patients.
Methods
Sixty patients with SLE were diagnosed by fulfilling the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE and sixty healthy age and sex matched control. All patients were subjected to full medical history and clinical examination. Activity was assessed using SLEDAI-2K score. Gene expression of Beclin-1, Bcl-2-L2, and Bcl-2 was measured.
Results
The study revealed that the expression of anti-apoptotic Bcl-2 and Bcl-2-L2 was significantly higher in SLE patients than control subjects, as well as the major apoptotic agent (Beclin-1) mRNA, p = 0.03, < 0.001 and 0.02, respectively. The apoptotic Beclin-1 mRNA was positively correlated with SLE disease severity index, r = 0.25; p = 0.0.4; therefore, our results showed that expression of the Beclin-1 was significantly higher in SLE patients than control (p < 0.02).
Conclusion
Our results showed that expression of the Beclin 1 were significantly higher in SLE patients than control (p < 0.02).
Background
The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity.
...Aim
We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients.
Methods
We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA.
Results
The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL;
p
< 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (
p
< 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (
p
= 0.01 for both) and positively correlated with disease duration (
r
= 0.45,
p
< 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (
p
< 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (
p
= 0.004). In juvenile SLE, the AUC was 0.65 and a
p
-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively.
Conclusion
YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features.
Objective
To investigate the characteristics, evolution, and visual outcome of non-infectious uveitis.
Methodology
Records of 201 patients with non-infectious uveitis (136 (67.7%) males and 84 ...(41.8%) juvenile-onset (≤ 16 years)) were retrospectively reviewed. Data were analyzed through Kruskal–Wallis and Mann–Whitney, chi-square (
χ
2
) tests, and logistic regression.
Results
The median disease and follow-up durations were 36 (interquartile range (IQR) 24–70) and 24 (IQR 10–36) months, respectively. Fifty-eight (28.9%) patients had persistently idiopathic uveitis, and 143 (71.1%) were associated with rheumatic diseases, of whom uveitis heralded, coincided with, and succeeded the rheumatic manifestation(s) in 62/143 (43.4%), 37/143 (25.9%), and 44/143 (30.7%) patients, respectively. Established rheumatic diseases were Behçet’s disease (103/201 (51.2%)), juvenile idiopathic arthritis (13/201 (6.5%)), sarcoidosis (8/201 (4%)), seronegative spondyloarthropathy (7/201 (3.5%)), and Vogt-Koyanagi-Harada (7/201 (3.5%)), and other diagnoses were present in 5/201 (2.5%) patients. Patients with idiopathic uveitis were characterized by a juvenile-onset (
p
< 0.001), lower male predominance (
p
= 0.01), prevalent granulomatous (
p
< 0.001), and anterior (
p
= 0.001) uveitis. The median visual acuity at last visit was 0.3 (IQR 0.05–0.6). Visual loss was present in 45/201 (22.3%) patients (36/201 (17.9%) unilateral and 9/201 (4.4%) bilateral). Apart from a longer disease duration (
p
= 0.002), lower educational level (
p
= 0.03), and prevalent panuveitis (
p
< 0.001), visual loss was not associated with any other studied ocular or extra-ocular characteristics.
Conclusion
Behçet’s disease (51.2%) and idiopathic uveitis (28.9%) were the most prevalent causes of non-infectious uveitis in our study. Visual loss (22.3%) was associated with a longer disease duration, lower education level, and prevalent panuveitis.
Key Points
• Most common causes of uveitis referred to rheumatologists were Behçet’s disease and idiopathic uveitis.
• Several rheumatic diseases initially presented only with uveitis, more commonly in adult and male patients.
• Panuveitis was more frequent among patients with an established rheumatic disease, whereas granulomatous uveitis was uncommon.
• Longer disease duration and presence of panuveitis were independently associated with visual loss.
Background
The effect of bronchial asthma on development of new-onset type 2 diabetes has not been studied.
Aim
The aim was to study the association of bronchial asthma and its severity with the ...incidence of type 2 diabetes after 5 years in patients without diabetes at the disease onset.
Patients and methods
A total of 200 consecutive patients with a physician diagnosis of bronchial asthma (120 not known to be diabetic and 80 known to have diabetes) presenting to the outpatient chest clinic in Kasr Alainy Hospital were included. Fasting blood glucose, 2h 75 g oral glucose tolerance test, glycated hemoglobin, and lipid profile were done. Spirometry, blood pressure, BMI, and other risk factors of diabetes were sought.
Results
Of the 120 nondiabetic patients, 30 patients met at least one criterion of prediabetes and 90 patients met at least one criterion of diabetes. Multivariable regression model demonstrated that forced vital capacity (FVC)%, maximal expiratory flow 75%, and inhaled bronchodilators are independent risk factors for elevated glycated hemoglobin, independent of inhaled or oral corticosteroids, family history, blood pressure, BMI, high-density lipoprotein, and triglycerides. Logistic multivariable regression model demonstrated that FVC% and forced expiratory volume in the first second % are independent risk factors for development of new-onset type 2 diabetes (hazard ratio for FVC%: 1.1589, 95% confidence interval: 1.0684–1.2571,
P
=0.0004; hazard ratio for forced expiratory volume in the first second %: 0.8754, 95% confidence interval: 0.8155–0.9396,
P
=0.0002).
Conclusion
The incidence of diabetes and prediabetes in patients with bronchial asthma who are not known to have diabetes at disease onset is 75 and 25%, respectively. Poor pulmonary function tests were independently associated with new-onset diabetes in such patients. This association is linked to the severity of asthma and not related to treatment.
Objectives:
In this study, we aimed to better understand the expression of pro-apoptotic Bad and Bax in the pathogenesis of systemic lupus erythematosus (SLE) and their relationship with the disease ...activity.
Patients and methods:
Between June 2019 and January 2021, a total of 60 female patients with SLE (median age 29 years; IQR, 25.0-32.0) and 60 age- and sex-matched healthy female controls (median age: 30 years; IQR, 24.0-32.0) were included. The Bax and Bad messenger ribonucleic acid (mRNA) expression was measured by real-time polymerase chain reaction.
Results:
The expression of Bax and Bad was significantly lower in SLE group than the control group. The median value of mRNA expression of Bax and Bad was 0.72 and 0.84, respectively versus 0.76 and 0.89 in the control group. The median value of (Bax*Bad)/β-actin index was 17.8 in the SLE group and 19.64 in the control group. The expression of both Bax, Bad and (Bax*Bad)/β-actin index had a good significant diagnostic utility (area under the curve AUC= 0.64, 0.70, and 0.65, respectively). The Bax mRNA expression showed a significant upregulation with disease flare-up. The efficacy of Bax mRNA expression in predicting SLE flare-up was good (AUC= 73%). In the regression model, the probability of flare-up reached 100%, with increasing Bax/β-actin as well, and the likelihood of flare-up increased 10,314 times with every unit increase of Bax/β-actin mRNA expression.
Conclusion:
Deregulation of the mRNA expression of Bax may have a role in the susceptibility to SLE and may be associated with disease flare. A better understanding of the expression of these pro-apoptotic molecules may carry a great potential for the development of specific effective therapies.
Nutritional status and unhealthy dietary habits may have an influence on Systemic Lupus Erythematosus (SLE) course and activity.
This work aimed to determine the nutritional status and dietary intake ...of SLE patients and its relation to disease activity.
Sixty-five SLE patients were recruited from Kasr Alainy outpatient clinic from October 2017 to December 2017 in a cross-sectional study. Data were collected using a structured interview questionnaire including inquiry about the socioeconomic status, nutritional status using anthropometric measurements, semi-quantitative food frequency questionnaires (FFQ), and hemoglobin level measurement. Disease activity level was assessed using SLE disease activity index (SLE-DAI).
The median age of the enrolled female patients was 30.0 (24.0–37.0), with median disease duration of 3.0 years (1.0–9.0). BMI assessment revealed that more than three quarters of SLE patients were overweight and obese. The semi-quantitative FFQ revealed a decreased consumption of fresh fruit, vegetables, milk and other dairy products and an increased intake of fats and oils. Disease activity (SLE-DAI) correlated with increased BMI (r=0.299, p=0.016), body weight (r=0.276, p=0.026), and disease duration (r=0.246, p=0.049).
Inadequate nutrient intake and the high percentage of overweight and obesity among SLE patients with excessive consumption of lipids and low intake of fibers were revealed. Also, disease activity (SLE-DAI) correlated with increased BMI.
El estado nutricional y los hábitos alimenticios poco saludables pueden influir en el curso y la actividad del lupus eritematoso sistémico (LES).
Este trabajo tuvo como objetivo determinar el estado nutricional y la ingesta dietética de los pacientes con LES y su relación con la actividad de la enfermedad.
Se reclutaron 65 pacientes con LES de la clínica ambulatoria de Kasr Alainy desde octubre de 2017 hasta diciembre de 2017 en un estudio transversal. Los datos se recopilaron mediante un cuestionario de entrevista estructurada que incluía una investigación sobre el estado socioeconómico, el estado nutricional mediante mediciones antropométricas, los cuestionarios de frecuencia de alimentos semicuantitativos (FFQ) y la medición del nivel de hemoglobina. El nivel de actividad de la enfermedad se evaluó utilizando el índice de actividad de la enfermedad del LES (LES-DAI).
La mediana de edad de las pacientes reclutadas fue de 30,0 (24,0-37,0) años, con una duración media de la enfermedad de 3,0 años (1,0-9,0). La evaluación del índice de masa corporal (IMC) reveló que más de las tres cuartas partes de las pacientes con LES tenían sobrepeso y eran obesas. La FFQ semicuantitativa reveló una disminución del consumo de frutas frescas, verduras, leche y otros productos lácteos, y una mayor ingesta de grasas y aceites. El índice del LES-DAI se correlacionó con un aumento del IMC (r=0,299; p=0,016), peso corporal (r=0,276; p=0,026) y duración de la enfermedad (r=0,246; p=0,049).
Se reveló una ingesta inadecuada de nutrientes y el alto porcentaje de sobrepeso y obesidad entre los pacientes con LES con un consumo excesivo de lípidos y una baja ingesta de fibras. Además, la actividad de la enfermedad (LES-DAI) se correlacionó con un aumento del IMC.
•Plasma ANCR, TINCR, HOTTIP and SPRY4-IT1 are novel candidate biomarkers of SSc.•SPRY4-IT1 could have clinical impact in diagnosis of SSc and its subtypes.•SPRY-IT1, HOTTIP and ANCR showed ...correlations with modified Rodnan skin score.•Deregulation of these skin-related lncRNAs widens the epigenetic landscape of SSc.•Correlations with disease manifestations link these lncRNAs to SSc pathology.
Systemic sclerosis or systemic scleroderma (SSc) is an inflammatory autoimmune disease whose pathogenesis remains ambiguous; however, epigenetics, including long noncoding RNAs (lncRNAs) is an emerging paradigm. To date, the expression, role and clinical significance of most lncRNAs in SSc remain unelucidated. Herein, we investigated the plasma expression profiles of lncRNAs; ANCR, TINCR, HOTTIP, and SPRY4-IT1, which were linked to skin biology, in SSc patients and its subtypes, their potential as diagnostic tools and their correlations with autoantibodies and disease manifestations. Sixty-three SSc patients and thirty-five healthy volunteers were recruited. Autoantibody profile (anti-Scl-70, anti-centromere, anti-RNA polymeraseIII, anti-ribonucleoprotein, antinuclear, and anti-phospholipid antibodies) was determined. lncRNAs analysis was conducted using RT-qPCR. Plasma TINCR, HOTTIP, and SPRY4-IT1 upregulation and ANCR downregulation were observed in SSc patients compared with controls. SPRY4-IT1 was superior in SSc diagnosis in ROC analysis and predicted its risk in multivariate logistic analysis. Plasma SPRT4-IT1 was higher in diffuse than limited SSc. SPRY4-IT1 and HOTTIP were positively correlated with modified Rodnan skin score while ANCR showed a negative correlation only in limited SSc. ANCR and TINCR were positively correlated with disease duration and ESR, respectively. ANCR and SPRY4-IT1 were positively correlated with pulmonary hypertension. HOTTIP was positively correlated with antinuclear antibody. SPRY4-IT1 was positively correlated with HOTTIP in the whole group, and with TINCR only in diffuse SSc. We introduce plasma SPRY4-IT1, HOTTIP, ANCR and TINCR as novel candidate biomarkers for SSc, with SPRY4-IT1 could predict SSc diagnosis and discriminate its subtypes. Our findings widen the epigenetic landscape of SSc and provide surrogates for future predictive studies.
Background
Behçet's disease (BD) is a chronic, multi-systemic, recurrent condition that affects the vascular, ocular, mucocutaneous, and central nervous systems. The diagnosis of this disease depends ...on its clinical features, which are similar to those observed in several diseases, such as Parkinson’s disease, pemphigus vulgaris, systemic lupus erythematosus, Crohn ҆s disease, and Sjӧgren’s syndrome. Lysosome-mediated autophagy is a catabolic, cytoprotective mechanism that maintains cell homeostasis by degrading undesired long-lived proteins and recycling nutrients. The aim of this study was to evaluate the correlations between some autophagy-related genes (
ATG5
,
ATG7
,
ATG12
,
LC3b
,
mTOR
) and the pathogenesis and immunopathology of BD. The expression levels of the genes were evaluated by quantitative polymerase chain reaction (qPCR) in 101 individuals that are classified into two groups. Group 1: (
n
= 71) BD patients, Group 2: (
n
= 30) healthy controls.
Results
Patients with BD had lower mRNA expression levels of
ATG5
and
mTOR
and higher levels of
LC3b
mRNA than the controls. No significant differences in the levels of both
ATG7
and
ATG12
were observed between the two groups. According to the area under the curve analysis,
LC3b
was considered the best candidate biomarker among the selected markers for the diagnosis of BD. The mRNA expression of
ATG5
was significantly correlated with patient age and the presence of oral ulcers. The mRNA expression of
ATG7
was significantly associated with age and the presence of erythema nodosum and vascular lesions, whereas that of
LC3b
was significantly correlated with the presence of pustules.
Conclusion
These findings indicated that elevated levels of
LC3b
were strongly associated with BD. Likewise, the levels of
ATG5
and
ATG7
were associated with the complications and outcomes of this disease. Additional assessments of the mRNA expression levels of these autophagy-related genes might prove beneficial in diagnosing this autoimmune disorder.
Background
Nogo-B is one of the members of the reticulon family. Nogo-B influences the proliferation of the hepatic stellate cells inducing liver fibrotic changes. We aimed at measuring the serum ...levels of Nogo-B in patients with chronic liver disease (CLD) with different etiologies. Ninety subjects were included, 18 of them were normal healthy individuals and 72 had liver disease (fibrosis/cirrhosis) with different etiologies: post-hepatitis C infection, post-hepatitis B infection, NASH, and autoimmune hepatitis. Serum Nogo-B was assessed using ELISA. Patients were subdivided according to the Child-Pugh score into 3 groups: group 1—Child A (24 patients); group 2—Child B (24 patients); and group 3—Child C (24 patients).
Results
Serum Nogo-B levels were found to be significantly higher in patients (1477.92 ± 1113.50) when compared with healthy control (301.28 ± 180.87) (
p
< 0.001). There was a statistically significant difference in serum Nogo-B level between the three sub-groups of patients (
p
< 0.001). A positive correlation was found between serum Nogo-B and MELD score (
r
= 0.46,
p
-value < 0.001). However, there was no correlation found between Nogo-B and FIB-4 index or APRI score. There was a significant positive correlation between serum Nogo-B level and coagulation profile and serum bilirubin. An inverse correlation was found between serum Nogo-B with serum albumin. A ROC curve was done to examine the validity of Nogo-B in the diagnosis of liver cirrhosis, and the area under the curve was found to be 0.979, a cutoff value of 600 with a sensitivity of 97.2% and a specificity of 94.4% (
p
-value < 0.001).
Conclusion
Nogo-B had a high value in the identification of patients with any severity of CLD. There is a highly significant correlation between Nogo-B and the synthetic function of the liver; it could be used as a measure of hepatic functional reserve.
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