Changes in serum immunoglobulin G glycosylation patterns for antiphospholipid syndrome patients with lectin microarray.

Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G-binding level of soybean agglutinin (p = 0.047, preferring N-acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (p = 0.001, recognized by Lotus tetragonolobus) and sialylation (p = 0.030, recognized by Sambucus nigra I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.

Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Machine Learning Reveals Serum Glycopatterns as Potential Biomarkers for the Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant chronic liver condition globally, and underdiagnosis is common, particularly in mild cases, attributed to the asymptomatic nature and traditional ultrasonography's limited sensitivity to detect early-stage steatosis. Consequently, patients may experience progressive liver pathology. The objective of this research is to ascertain the efficacy of serum glycan glycopatterns as a potential diagnostic biomarker, with a particular focus on the disease's early stages. We collected a total of 170 serum samples from volunteers with mild-NAFLD (Mild), severe-NAFLD (Severe), and non-NAFLD (None). Examination via lectin microarrays has uncovered pronounced disparities in serum glycopatterns identified by 19 distinct lectins. Following this, we employed four distinct machine learning algorithms to categorize the None, Mild, and Severe groups, drawing on the alterations observed in serum glycopatterns. The gradient boosting decision tree (GBDT) algorithm outperformed other models in diagnostic accuracy within the validation set, achieving an accuracy rate of 95% in differentiating the None group from the Mild group. Our research indicates that employing lectin microarrays to identify alterations in serum glycopatterns, when integrated with advanced machine learning algorithms, could constitute a promising approach for the diagnosis of NAFLD, with a special emphasis on its early detection.

Serum Clusterin Concentration and Its Glycosylation Changes as Potential New Diagnostic Markers of SARS-CoV-2 Infection and Recovery Process.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. Glycoprotein clusterin (CLU) has many functions such as phagocyte recruitment, complement system inhibition, apoptosis inhibition, hormone and lipid transport, as well as in the immune response. The study aimed to assess the changes in CLU concentrations and the profile and degree of CLU glycosylation between patients with severe COVID-19, convalescents, and healthy subjects (control). The profile and degree of serum CLU N-glycosylation were analyzed using lectin-ELISA with specific lectins. CLU concentrations were significantly lower and relative reactivities of CLU glycans with SNA (Sambucus nigra agglutinin) were significantly higher in severe COVID-19 patients in comparison to convalescents and the control group. The relative reactivities of CLU glycans with MAA (Maackia amurensis agglutinin), together with relative reactivity with LCA (Lens culinaris agglutinin), were also significantly higher in patients with severe COVID-19 than in convalescents and the control group, but they also significantly differed between convalescents and control. The development of acute inflammation in the course of severe COVID-19 is associated with a decrease in CLU concentration, accompanied by an increase in the expression of α2,3-linked sialic acid, and core fucose. Both of these parameters can be included as useful glycomarkers differentiating patients with severe COVID-19 from convalescents and the control group, as well as convalescents and healthy subjects.

Angiogenic factors and the lectin pathway of complement in women with secondary recurrent pregnancy loss.

The poor remodeling of placental spiral arteries seen in preeclampsia is also discussed to contribute to recurrent pregnancy loss (RPL) preceded by abnormal angiogenesis and excessive complement activation. Low levels of Mannose-binding-lectin (MBL), a pattern recognition molecule (PRM) of the lectin pathway, have been found in women with RPL. We propose that pregnancy loss is connected to defective angiogenesis with reperfusion damage in the placenta and decreased levels of PRM in the lectin pathway in women with RPL. In this cohort study, we investigate the angiogenic factors and the lectin complement pathway in early pregnancy and their time-dependent relationship with pregnancy outcomes in 76 women with secondary RPL (sRPL) who have at least four prior pregnancy losses and a live birth. We evaluated levels of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Vascular Endothelial Growth Factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PRMs, MBL, ficolin-1, -2, -3 and an additional soluble PRM, Pentraxin-3, during the 5th, 6th, and 7th gestational weeks. Our results showed that, compared to live births, pregnancies that ended in loss were associated with elevated VEGF levels and decreased levels of the Ang-2/Ang-1 ratio. Also, increasing levels of ficolin-2 were significantly associated with pregnancy loss, with MBL showing no association. Our research suggests that women with sRPL may have inadequate placentation with impaired angiogenesis in pregnancies ending in a loss.

Omentin associates with serum metabolite profiles indicating lower diabetes risk: KORA F4 Study.

INTRODUCTION: Circulating omentin levels have been positively associated with insulin sensitivity. Although a role for adiponectin in this relationship has been suggested, underlying mechanisms remain elusive. In order to reveal the relationship between omentin and systemic metabolism, this study aimed to investigate associations of serum concentrations of omentin and metabolites. RESEARCH DESIGN AND METHODS: This study is based on 1124 participants aged 61-82 years from the population-based KORA (Cooperative Health Research in the Region of Augsburg) F4 Study, for whom both serum omentin levels and metabolite concentration profiles were available. Associations were assessed with five multivariable regression models, which were stepwise adjusted for multiple potential confounders, including age, sex, body mass index, waist-to-hip ratio, lifestyle markers (physical activity, smoking behavior and alcohol consumption), serum adiponectin levels, high-density lipoprotein cholesterol, use of lipid-lowering or anti-inflammatory medication, history of myocardial infarction and stroke, homeostasis model assessment 2 of insulin resistance, diabetes status, and use of oral glucose-lowering medication and insulin. RESULTS: Omentin levels significantly associated with multiple metabolites including amino acids, acylcarnitines, and lipids (eg, sphingomyelins and phosphatidylcholines (PCs)). Positive associations for several PCs, such as diacyl (PC aa C32:1) and alkyl-alkyl (PC ae C32:2), were significant in models 1-4, whereas those with hydroxytetradecenoylcarnitine (C14:1-OH) were significant in all five models. Omentin concentrations were negatively associated with several metabolite ratios, such as the valine-to-PC ae C32:2 and the serine-to-PC ae C32:2 ratios in most models. CONCLUSIONS: Our results suggest that omentin may influence insulin sensitivity and diabetes risk by changing systemic lipid metabolism, but further mechanistic studies investigating effects of omentin on metabolism of insulin-sensitive tissues are needed.

Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

PURPOSE: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. STUDY DESIGN: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. RESULTS: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. CONCLUSIONS: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

Association of Intelectin 1 Gene rs2274907 A > T Polymorphism with Obesity, Type 2 Diabetes, Serum Intelectin-1 Levels and Lipid Profiles in Turkish Adults.

The anti-inflammatory adipokine intelectin-1, which is encoded by the ITLN1 gene, is hypothesized to be linked to the pathogenesis of type 2 diabetes (T2DM) and obesity. The purpose of this study was to examine the effect of the ITLN1 gene polymorphism rs2274907 on obesity and T2DM in Turkish adults. The impact of genotype on lipid profiles and serum intelectin levels in the obese and diabetes groups was also investigated. Randomly selected 2266 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish adult risk factor study were cross-sectionally analyzed. The genotyping of rs2274907 A > T polymorphism was performed by using the hybridization probe based LightSNiP assay in real-time PCR. T2DM were defined using the criteria of the American Diabetes Association. Obesity was described as Body mass index ≥ 30 kg/m2. Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. According to findings, there was no vital connection between the rs2274907 polymorphism and obesity, T2DM, or serum intelectin-1 level. The TA+AA carriers had significantly higher triglyceride levels (p = 0.007) compared with the TT carriers in both obese and T2DM women when adjusted for relevant covariates. ITLN1 rs2274907 polymorphism is not correlated with the risk of obesity and T2DM and not affect serum ITLN1 levels in Turkish adults. However, this polymorphism appears to be important in regulating triglyceride levels in obese and diabetic women.

Lower circulating omentin-1 is independently linked to subclinical hypothyroidism reflecting cardiometabolic risk: an observational case-control and interventional, longitudinal study.

BACKGROUND: Omentin-1, a newly discovered adipokine, is implicated in the modulation of the adipose phenotype, ameliorating systemic metabolism and exhibiting anti-atherogenic, anti-oxidative, cardioprotective, anti-inflammatory and insulin-sensitizing properties. Our goal was to explore circulating omentin-1 in subclinical hypothyroidism (SH) and determine its correlations with cardiometabolic risk factors. METHODS: In a large case-control and interventional longitudinal study, serum omentin-1, metabolic and lipid parameters, inflammatory biomarkers, classic adipocytokines and cardiovascular risk factors were assessed in 120 consecutive patients with SH and 120 healthy controls matched on age, gender and date of blood draw. Sixteen patients with SH were administered L-T4 and, after six months, circulating omentin-1 and other biomarkers were determined. RESULTS: SH subjects presented significantly decreased circulating omentin-1 than control individuals (P<0.001). In all study participants, omentin-1 was negatively correlated with TSH, anti-thyroid antibodies, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, adipokines and cardiovascular risk factors, including Framingham score and apolipoprotein B. Omentin-1 was positively associated with adiponectin and HDL-C. Circulating omentin-1 was independently associated with SH occurrence, above and beyond clinical and cardiometabolic factors (P=0.04). TSH was a negative independent predictor of serum omentin-1 levels (P<0.001). L-T4 treatment did not alter considerably the lower omentin-1 levels in treated SH patients (P=0.07). CONCLUSIONS: Omentin-1 may be a useful non-invasive biomarker reflecting cardiometabolic risk as well as a promising therapeutic target. More mechanistic and larger prospective studies shedding light on the pathogenetic role of omentin-1 in SH are required to confirm these findings.

Sortilin/Omentin-1 ratio in peripheral artery disease: A cross-sectional study on 295 unselected elderly patients.

BACKGROUND: The role of sortilin and omentin-1 in the pathogenesis of atherosclerosis and vascular disease is an emerging topic in recent years. These molecules can be found circulating in the blood. Recent studies have shown how these biomarkers appear to correlate with the severity of PAD. The levels of these molecules appear to be inversely proportional to each other. Their relationship may provide further insight into the management of the very old diabetic patients with PAD. This study aimed to assess the possible role of sortilin/omentin-1 ratio as easy-to-measure marker in peripheral artery disease (PAD) in type-2 diabetic patients. METHODS: This study analyzed the association between sortilin and omentin-1 serum levels and the presence of clinically significant lower limb PAD in diabetic individuals. We enrolled 295 diabetic patients, including 179 with PAD. Serum levels were collected and correlated with clinical characteristics of the patients. RESULTS: Sortilin concentration was significantly higher in the latter group compared to the former and there was a trend toward increased sortilin levels as disease severity increased. Omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls and the levels gradually decreased in proportion to disease severity. The ratio of sortilin to omentin-1 was significantly higher in patients with PAD compared to the other group. CONCLUSION: The sortilin to omentin-1 ratio appears to be a predictive factor for PAD in patients with type-2 diabetes and it may be a promising marker for clinically significant atherosclerosis of the lower limbs. Further studies are needed to confirm this finding and to evaluate its clinical usefulness.

Assessment of the Diagnostic Utility of Serum Omentin 1 and IL-6 in Early Stages of Diabetic Nephropathy.

In India, diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Timely detection of microalbuminuria and appropriate intervention can reverse or arrest the progress of nephropathy. The pathogenesis of diabetic nephropathy has revealed that during the early onset of kidney involvement in diabetics, inflammation and fibrosis progress from tubular to glomerular damage. This study was designed to elucidate the association of chemokines, Omentin 1, and interleukin 6 (IL-6) with microalbuminuria. MATERIAL: Settings and Design: This cross-sectional observational study was conducted as a collaborated study in the Departments of General Medicine and Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, India, during 2019-2020. METHODS AND MATERIAL: Our study group comprised 116 diabetes mellitus patients. They were grouped into two, each of 58 on the basis of their urine albumin levels; Group 1 (controls) had UACR < 30 µg/mg, eGFR> 90ml/ min and Group 2 (cases) had UACR ≥ 30 µg/mg and < 300 µg/mg, eGFR>60ml/min and < 90ml/min. Serum omentin 1 and IL-6, creatinine, glycated haemoglobin (HbA1c), fasting (FBS) and postprandial blood sugar (PPBS), lipid profile, total protein, albumin, and fasting insulin, HOMA-IR were studied. OBSERVATION: Our study showed that Omentin 1 levels were decreased, and IL-6 levels were increased in the DN group compared to the T2DM without DN. The risk estimates calculated revealed that diabetes mellitus patients having an IL-6: omentin ratio ≥ 0.26 had Odds of 3.97 of developing DN, which was statistically significant (CI 2.36-6.68). Therefore, a ratio of ≤ 0.26 was found to be kidney protective among diabetes mellitus patients. CONCLUSION: From the results of this present study, we recommend that estimation of serum IL-6: omentin 1 ratio of T2DM will aid in identifying early stages of DN before the onset of microalbuminuria.

A Randomized Trial with Two Hypocaloric Diets with Different Lipid Profiles and Effects on Serum Omentin-1 Levels in Obese Subjects.

Background: The effects of weight loss therapies on omentin-1 levels have been unclear, showing both elevations and decreases in circulating levels. The role of dietary fat might have an important role. The aim of our investigation was to evaluate the influence of weight decrease on omentin-1 levels after two different high-fat hypocaloric diets. Methods: 319 Caucasian obese subjects were randomly allocated during 12 weeks (Diet M (high monounsaturated fat diet) vs. Diet P (high polyunsaturated fat diet)). The mean age was 47.2 ± 5.0 years (range: 26-64), and the mean body mass index (BMI) was 37.9 ± 4.1 kg/m2 (range: 30.6-39.8). Sex distribution was 237 females (74.7%) and 72 males (25.3%). Anthropometric and biochemical parameters were evaluated at basal and after both diets. SPSS 23.0 has been used to realize univariant and multivariant statistical analysis. Results: After both diets, BMI, weight, fat mass, waist circumference, systolic blood, LDL-cholesterol, insulin levels, and HOMA-IR decreased in a statistical way from basal values. These improvements were similar in both diets. After Diet P, omentin-1 levels increase (21.2 ± 9.1 ng/ml: P = 0.02), and after Diet M, this adipokine increases (47.1 ± 11.2 ng/ml: P = 0.02), too. The increase of omentin-1 with Diet M was statistically significantly higher than that after Diet P (P = 0.01). A multiple regression analyses adjusted by age and sex reported a statistical relation between BMI (kg/m2) and insulin (UI/L) with omentin-1 levels. Conclusions: Our study demonstrated a significant improvement on serum omentin-1 levels after weight loss secondary to both diets; in contrast, omentin-1 improvement was higher with Diet M than with Diet P.

High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with Obesity.

We investigated the effects of 12 weeks of high-intensity interval training (HIIT) on selected circulating adipokines and other cardiovascular diseases risks factors in men with obesity. Thirty men with obesity (age: 24.96±3.11 year, BMI: 30.92±1.04 kg/m2) were randomly assigned to HIIT and control groups. The HIIT group participated in a 12-week HIIT program (5×2 min interval bout at an intensity of 85-95% HRmax interspersed by 1 min passive recovery, three times per week), while the control group maintained their usual lifestyles. Blood lipids, insulin resistance, and select serum adipokines were assessed before and after 12 weeks of the intervention period. HIIT improved body composition and lipid profiles (p<0.05) and also decreased fasting insulin levels (p=0.001) and HOMA-IR (p=0.002) levels. Furthermore, HIIT increased levels of lipocalin-2 (p=0.002) while decreasing omentin-1 levels (p=0.001) in men with obesity. Changes in lcn2 and omentin-1 concentrations correlated with the changes in risk factors in the HIIT group (p<0.05). The results indicate that 12 weeks of supervised HIIT significantly improves both circulating concentrations of lcn2 and omentin-1, two recently described adipokines, and risk markers of cardiovascular diseases in men with obesity. Further research is necessary to understand the molecular mechanisms involved with these changes.

Omentin-1 and its relationship with inflammatory factors in maternal plasma and visceral adipose tissue of women with gestational diabetes mellitus.

PURPOSE: To investigate the association of omentin-1 and inflammatory factors in serum and visceral adipose tissue (VAT) of women with gestational diabetes mellitus (GDM) compared to normal pregnant (NP) subjects. Furthermore, to examine their correlation with maternal clinical characteristics. METHODS: We compared 116 GDM women to 115 NP women, at the time of cesarean section. Circulating omentin-1 and pro-inflammatory (IL-1ß, IL-6, TNF-α), and anti-inflammatory cytokines (IL-1RA, IL-10) were examined. Moreover, their mRNA expression in VAT, along with inflammatory factors involved in the NF-κB pathway (TLR2, TLR4, NF-κB, IKκB), were examined. RESULTS: Circulating omentin-1 (p = 0.022) was lower and circulating IL-1-ß, IL-1RA, as well as IL-10 (p = 0.005, p = 0.007, and p = 0.015, respectively), were higher in GDM compared to NP women. Omentin-1 correlated negatively with pre-pregnancy and gestational BMI, and HOMA-IR in all women, but was not associated with cytokines. TLR2, TLR4, IL-1ß, IL-1RA, IL-6, IL-10 mRNA expression in VAT was lower in GDM compared with controls (p < 0.05 all). In multivariate analysis, BMI at delivery was significantly correlated to omentin-1 concentrations in all and NP subjects. In addition, omentin-1 expression was correlated to inflammatory gene expression in all, GDM and NP, women (p < 0.05 all). CONCLUSION: Serum levels and VAT gene expression of omentin-1 are not independently linked to GDM; notwithstanding, GDM women have a VAT-altered inflammatory status. In addition, no systemic association between omentin-1 and inflammatory factors was found, whereas associations between their expression in all women were observed, indicating that expression of these adipokines is linked between them regardless of GDM.

The impact of omentin-1 gene polymorphisms (rs2274907 and rs2274908) on serum lipid concentrations and coronary artery disease in a sample of Iraqi individuals (A pilot study).

BACKGROUND: Coronary artery disease (CAD) is the primary cause of death worldwide. It is mainly caused by atherosclerosis that initiates from a genetic-environmental interaction. Studies highlighted the association of numerous gene polymorphisms with CAD. Omentin-1 is secreted from visceral adipose tissues, intestine, and others; it has anti-inflammatory and insulin sensitivity improving roles. AIM: To explore the association of the omentin-1 gene polymorphisms (rs2274907 and rs2274908) with serum lipid concentrations and CAD in a sample of the Iraqi population. METHODS: A case-control study was followed, in which CAD patients were analyzed versus a group of healthy persons. Serum lipid concentrations were measured by enzymatic methods. Genotyping of the omentin-1 gene for rs2274907 SNP was achieved by ARMS-PCR, while for rs2274908 SNP by allele-specific PCR (AS-PCR) techniques. RESULTS: Atherogenic serum lipid concentrations increased significantly in CAD patients relative to the control group. Genotyping of the omentin-1 gene for rs2274907 SNP revealed a significant (OR = 4.11, P = 0.035) elevation of the AT genotype carriers in CAD versus the control groups. The genotype analysis of the rs2274908 SNP failed to exhibit a significant variation. The two analyzed SNPs were indicated to be in linkage disequilibrium (r = 0.772, P < 0.0001). The global haplotype association of the 2 SNPs was demonstrated to be significant (P = 0.006). Serum lipid concentrations were found to be independent of the genotype distribution of the rs2274907 SNP. CONCLUSION: Carriers of the AT genotype of rs2274907 SNP in the omentin-1gene may have a four-fold risk of developing CAD compared to those of the wild genotype. Alterations of serum lipid concentrations may do not depend on the genotypes of this SNP.

Polymorphisms of the FCN2 Gene 3'UTR Region and Their Clinical Associations in Preterm Newborns.

Ficolin-2 is regarded as an important innate immunity factor endowed with both lectin (carbohydrate recognition) qualities and ability to induce complement activation. The aim of this study was to investigate the association of the FCN2 3'-untranslated region (3'UTR) polymorphisms with ficolin-2 expression and perinatal complications in preterm neonates. The sequencing analysis allowed us to identify six 3'UTR polymorphisms with minor allele frequency (MAF) >1%: rs4521835, rs73664188, rs11103564, rs11103565, rs6537958 and rs6537959. Except for rs4521835, all adhered to Hardy-Weinberg expectations. Moreover, rs6537958 and rs6537959 were shown to be in perfect linkage disequilibrium (LD) with nine other genetic polymorphisms: rs7040372, rs7046516, rs747422, rs7847431, rs6537957, rs6537960, rs6537962, rs11462298 and rs7860507 together stretched on a distance of 1242 bp and very high LD with rs11103565. The 3'UTR region was shown to bind nuclear extract proteins. The polymorphisms at rs4521835 and rs73664188 were found to influence serum ficolin-2 concentration significantly. All polymorphisms identified create (together with exon 8 polymorphism, rs7851696) two haplotype blocks. Among 49 diplotypes (D1-D49) created from rs7851696 (G>T), rs4521835 (T>G), rs73664188 (T>C), rs11103564 (T>C), rs11103565 (G>A) and rs6537959 (T>A), twenty two occurred with frequency >1%. Two diplotypes: D13 (GTTTGT/GGTCGT) and D10 (GTTTGT/GGTCGA), were significantly more frequent among preterm neonates with early onset of infection and pneumonia, compared with newborns with no infectious complications (OR 2.69 and 2.81, respectively; both p<0.05). The minor (C) allele at rs73664188 was associated with an increased risk of very low (≤1500 g) birthweight (OR=1.95, p=0.042) but was associated with the opposite effect at rs11103564 (OR=0.11, p=0.005).

Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes.

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Changes of omentin-1 and chemerin during 4 weeks of lifestyle intervention and 1 year follow-up in children with obesity.

AIMS: Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce. METHODS: In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs). RESULTS: Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p < 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p < 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p < 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p < 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p < 0.001). CONCLUSION: Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss. TRIAL REGISTRATION: ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754.

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial.

BACKGROUND: The innate and adaptive immune system is involved in the airway inflammation associated with acute exacerbations in patients with chronic obstructive pulmonary disease (COPD). We evaluated the association of mannose-binding lectin (MBL), immunoglobulin (Ig) and ficolin-2 concentrations with COPD exacerbations and according to the glucocorticoid treatment duration for an index exacerbation. METHODS: Post-hoc analysis of the randomized, double-blind, placebo-controlled REDUCE trial of 5 vs. 14 days of glucocorticoid treatment for an index exacerbation. MBL, ficolin-2 and total IgG/IgA and subclass concentrations were determined in stored samples drawn (n = 178) 30 days after the index exacerbation and associated with the risk of re-exacerbation during a 180-day follow-up period. RESULTS: IgG and subclass concentrations were significantly lower after 14 days vs. 5 days of glucocorticoid treatment. Patients with higher MBL concentrations were more likely to suffer from a future exacerbation (multivariable hazard ratio 1.03 per 200 ng/ml increase (95% confidence interval (CI) 1.00-1.06), p = 0.048), whereas ficolin-2 and IgG deficiency were not associated. The risk was most pronounced in patients with high MBL concentrations, IgG deficiency and 14 days of glucocorticoid treatment pointing towards an interactive effect of MBL and IgG deficiency in the presence of prolonged glucocorticoid treatment duration [Relative excess risk due to interaction 2.13 (95% CI - 0.41-4.66, p = 0.10)]. IgG concentrations were significantly lower in patients with frequent re-exacerbations (IgG, 7.81 g/L vs. 9.53 g/L, p = 0.03). CONCLUSIONS: MBL modified the short-term exacerbation risk after a recent acute exacerbation of COPD, particularly in the setting of concurrent IgG deficiency and recent prolonged systemic glucocorticoid treatment. Ficolin-2 did not emerge as a predictor of a future exacerbation risk.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.