Milk fat globule E-8 and interleukin 17 in systemic lupus erythematosus: partners in crime?

Objectives

Systemic lupus erythematosus (SLE) is a multi-factorial, autoimmune disease with a wide array of manifestations. The pro-inflammatory cytokine interleukin (IL)-17 has been implicated in the inflammatory response and tissue damage in SLE; however, its correlation with disease activity is still questionable. Meanwhile, efficient clearance of apoptotic cells is required for immune tolerance. An abnormally low or high level of milk fat globule (MFG-E8) can result in impaired apoptotic cell clearance and the subsequent autoimmune response. In this study, we endeavoured to compare the levels of MFG-E8 and IL-17 in SLE patients and healthy controls and to reveal the alleged association of these levels with SLE disease activity.

Material and methods

Serum samples from 57 SLE patients and 30 healthy control subjects were examined for quantitation of MFG-E8 and IL-17 levels using ELISA. Systemic lupus erythematosus disease activity was calculated using the SLE Disease Activity Index (SLEDAI). Clinical manifestations and laboratory findings of the patients were also recorded.

Results

We report that serum MFG-E8 levels were significantly elevated in the sera of SLE patients compared to healthy controls (p-value = 0.019). Likewise, IL-17 levels were higher in SLE patients (p-value < 0.001). A positive correlation was revealed between MFG-E8 level and proteinuria. Surprisingly, there was a poor correlation between disease activity and the levels of either IL-17 or MFG-E8.

Conclusions

Although serum MFG-E8 and IL-17 levels were higher in SLE patients than in normal controls, our results indicate that they cannot accurately reflect the disease activity. Meanwhile, further studies are needed to assess MFG-E8 and IL-17 as potential therapeutic targets in SLE patients.     

A two-step human culture system replicates intestinal monocyte maturation cascade: Conversion of tissue-like inflammatory monocytes into macrophages

Monocyte maturation program into macrophages (MΦ) is well defined in murine gut under homeostatic or inflammatory conditions. Obviously, in vivo tracking of monocytes in inflamed tissues remains difficult in humans. Furthermore, in vitro models fall short in generating the surrogates of transient extravasated tissue inflammatory monocytes. Here, we aimed to unravel environmental cues that replicated the human monocyte “waterfall” process in vitro by first, generating tissue-like inflammatory monocytes, which were then shifted toward MΦ. Purified CD14⁺CD16⁻ monocytes, cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ and IL23, differentiated into CD14⁺CD163⁻ cells that displayed a monocyte-like morphology. In vitro generated inflammatory CD14⁺CD163⁻ (inflammatory monocyte-like cells) cells promoted IL-1β-dependent memory Th17 and Th17/Th1 responses, like the CD14⁺CD163⁻ mo-like cells that accumulate in inflamed colon of Crohn's disease patients. Next, in vitro generated inflammatory monocyte-like cells converted to functional CD163⁺ MΦ following exposure to TGF-β and IL10. Gene set enrichment analysis further revealed a shared molecular signature between converted CD163⁺ MΦ and MΦ detected in various inflamed nonlymphoid and lymphoid diseased tissues. Our findings propose a two-step in vitro culture that recapitulates human monocyte maturation cascade in inflamed tissue. Manipulation of this process might open therapeutic avenues for chronic inflammatory disorders.     

Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma

Immunologic Research - Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide...     

Effects of opioid (tramadol) treatment on testicular functions in adult male rats: The role of nitric oxide and oxidative stress

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The 6-min walk test: an independent correlate of elevated tricuspid regurgitant jet velocity in children and young adult sickle cell patients

Elevation of echocardiography-determined tricuspid regurgitant jet velocity (TRV) predicts high systolic pulmonary artery pressure. The present study tested the hypotheses that elevated tricuspid regurgitant jet velocity is associated with both hemolysis and hypoxia and abnormal 6-min walk test (6MWT) results. This study aims to correlate elevated TRV with different clinical laboratory findings and 6MWT and to find the independent predictors of increased TRV. A prospective study of 80 patients aged 5–25 years old with sickle cell disease (SCD) under basal conditions and 40 matched controls was conducted. Hemolytic analysis was assessed by the levels of lactate dehydrogenase, serum bilirubin, and reticulocyte count. Oxygen saturation determination using pulse oximeter and 6MWT were done. The overall prevalence of elevated TRV (≥2.5 m/s) was 28.75 %. Associated risk factors were older age (r?=?0.28, p?=?0.01), longer duration of disease (r?=?0.25, p?=?0.025), higher reticulocytic count (r?=?0.344, p?=?0.002), lower O₂ saturation (r?=??0.574, p?=?0.0001), and shorter walked distance in 6MWT (r?=??0.75, p?=?0.0001). By multivariate logistic analysis, only the distance walked during 6MWT was the independent correlate of elevated TRV (odds ratio?=?0.85; 95 % CI?=?0.74 to 0.98 p?=?0.033). The study provides evidence for independent association of TRV with abnormal 6MWT results. The 6-min walk test can be used as noninvasive adjuvant tool for functional capacity assessment of SCD patients with elevated TRV.     

JAK2V617F allele burden in patients with myeloproliferative neoplasms

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Egy-Score as a Noninvasive Score for the Assessment of Hepatic Fibrosis in Chronic Hepatitis C: A Preliminary Approach

Background and Aims:

Egy-Score is a new noninvasive score for prediction of severe hepatic fibrosis in patients with chronic liver diseases. The aim of this study was to validate Egy-Score as a noninvasive score for predicting stage of hepatic fibrosis in a group of Egyptian chronic hepatitis C patients.

Patients and Methods:

One hundred Egyptian patients with chronic hepatitis C were enrolled. Mean age was 40.25 ± 9.39 years. They were subjected to CA19-9, alpha-2-macroglobulin, total bilirubin, platelet count and albumin, liver biopsy, and histopathological staging of hepatic fibrosis according to METAVIR scoring system as part of their assessment for treatment. Egy-Score was calculated according to the following formula: Egy-Score = 3.52 + 0.0063 × CA19-9 + 0.0203 × age + 0.4485 × alpha-2-macroglobulin + 0.0303 × bilirubin – 0.0048 × platelet – 0.0462 × albumin. Egy-Score results were correlated to the stage of hepatic fibrosis.

Results:

Egy-Score correlates positively with the stage of hepatic fibrosis (F0–F4). Egy-Score was able to differentiate significant hepatic fibrosis, severe hepatic fibrosis, and cirrhosis accurately. Cutoff values of Egy-Score were 2.91850 (for significant fibrosis), 3.28624 (for severe fibrosis), and 3.67570 (for cirrhosis). Sensitivity, specificity, and areas-under-ROC curve (AUROCs) were 75.8%, 68.42%, and 0.776 (for significant fibrosis “≥F2”), 91.67%, 77.63%, and 0.875 (for severe fibrosis “≥F3”), and 81.82%, 86.52%, and 0.874 (for cirrhosis “F4”), respectively.

Conclusion:

Egy-Score is a useful noninvasive panel of surrogate biomarkers that could accurately predict different stages of hepatic fibrosis in patients with chronic hepatitis C.     

Late-onset systemic lupus erythematosus: characteristics and outcome in comparison to juvenile- and adult-onset patients—a multicenter retrospective cohort

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