To Örebro University

Aim of the study: Idiopathic inflammatory myopathies (IIM) are autoimmune diseases with a low prevalence and incidence worldwide. The levels of IFN-gamma production by T-lymphocytes are related to disease activity. IFN-gamma +874 T/A (rs2430561) has been shown to alter the serum levels of IFN-gamma in different pathologies. The aim of this work is to explore the role of IFN-gamma +874 T/A polymorphism in IIM.

Methods: Using a specific sequence primer-polymerase chain reaction (SSP-PCR), the genotype was defined for normal healthy controls (HC) and patients with IIM. Markers of muscle damage, clinical features and treatment were collected from chart at the time of diagnosis and at recruitment point. All the data were analyzed by demographic characteristics, genotype, type of IIM, treatment, clinical features, and enzymatic levels.

Results: No association was found comparing the genotypes or alleles of the IIM patients vs. HC. On the other hand, the TT genotype, previously described as a high producer of INF gamma, showed higher levels of CPK at diagnosis in IIM patients, whereas females at diagnosis and males in remission presented higher levels.

Conclusions: Even with a limited number of patients due to the rarity of this disease, no association was found between the disease development. Further, the TT genotype promoted muscle damage due to CPK elevation in the sera compared to the TA/AA genotype in patients with IIM. This could be genetic evidence of the impact of IFN-gamma in the disease activity of IIM patients. A larger cohort is needed to confirm these results.

INTRODUCTION: Peripheral arterial disease (PAD), including intermittent claudication (IC) or critical limb ischemia (CLI), can be treated with endovascular revascularization; however, tools for intraoperative prognostication are limited. The In-Vivo Optical Spectroscopy (INVOS) system, a non-invasive near-infrared spectroscopy device, measures tissue oxygenation. This pilot study aims to investigate the use of INVOS during endovascular surgery for PAD as a prognostic tool for endovascular PAD treatment. This study is intended as a feasibility and hypothesis-generating pilot, rather than one designed to draw definitive conclusions.

METHODS: Thirty patients with PAD undergoing endovascular treatment were prospectively enrolled. In-Vivo Optical Spectroscopy sensors were applied to the treated foot preoperatively. Measurements were recorded preoperatively, postoperatively, and at 1, 2, and 3 hours post-surgery. Raw INVOS values and INVOS/systolic blood pressure (SBP) ratios were calculated and normalized to baseline values to determine fold changes. Clinical outcomes were assessed at 30 days.

RESULTS: No significant changes in raw INVOS or SBP values were observed before or after the procedure in both IC and CLI groups. However, the normalized INVOS/SBP ratio was significantly higher in IC patients at 1 and 2 hours postoperatively (p<0.05). A fold change greater than 1.25 was associated with better clinical outcomes, including fewer complications and higher rates of patient- and physician-reported improvement.

CONCLUSION: An INVOS/SBP ratio fold change greater than 1.25-fold is associated with improved outcomes following endovascular intervention for PAD. In-Vivo Optical Spectroscopy may serve as a valuable intraoperative prognostic tool, particularly in IC patients. Further studies are needed to validate these findings.Clinical ImpactThe clinical impact of the current work is to improve the knowledge in the application of INVOS measurements peri operative in clinical practices and improve patients care. Post operative surveillance with INVOS could be used to confirm surgical success. INVOS ratio lower than 1.25-fold after first revascularization should be reassessed and improve blood flow towards the limb. Although limited, this pilot study shows that the use of INVOS can be an adjuvanted tool in monitoring surgical outcomes in patients with PAD.

In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs). Silencing RSAD2 in IFN-γ-stimulated hAoSMCs resulted in reduced expression and secretion of key CXCR3-chemokines, CXCL9, CXCL10, and CXCL11. Conditioned medium from RSAD2-deficient hAoSMCs exhibited diminished monocyte attraction in vitro compared to conditioned medium from control cells. Furthermore, RSAD2 transcript was elevated in carotid lesions where it was expressed by several different cell types, including endothelial cells, macrophages and smooth muscle cells. Interestingly, RSAD2 displayed significant correlations with CXCL10 (r =  0.45, p = 0.010) and CXCL11 (r = 0.53, p = 0.002) in human carotid lesions. Combining our findings, we uncover a novel role for RSAD2 in hAoSMCs, which could potentially contribute to monocyte recruitment in the context of atherosclerosis.

Background: Atherosclerosis is a cardiovascular disease, highly predictable, and associated with different atherogenic indices (AI) in adults. However, such indexes in the pediatric population are far less explored. The objective of this study was to evaluate the AI and the cardiovascular factors in the pediatric population in the South-Southeast of Mexico.

Methods: A total of 481 children between 2 and 17 years old were recruited. Anthropometric evaluation, blood pressure (BP), lipid profile, apolipoprotein A-I (ApoA-I) and apolipoprotein B (ApoB) were measured, and AI were calculated. The population was grouped by age, binary logistic regression analysis was performed to analysis for associations of AI and cardiovascular risk factors. Sensibility and specificity of AI to detect metabolic alteration were evaluated for curve ROC.

Results: The atherogenic risk presented a high prevalence in the pediatric population, such as LDL-c/ApoB (86.9%), AIP (78%) and AC (36.6%). Preschoolers showed a higher risk of ApoB/ApoA-I and ApoB/LDL-c, while adolescents have a high risk of AIP. CRI-I and AC were associated with elements of lipid profile and body mass index (BMI). ROC curves analysis shows that AIP is the best index evaluating metabolic syndrome (MS) (0.87) and dyslipidemia (0.91).

Conclusion: Such pediatric population showed a high risk of AI, mainly by LDL-c/ApoB and AIP. The BMI was the cardiovascular risk factors most frequently related to AI, AIP is the best index for detecting cases of MS and dyslipidemia. This is the first study carried out in the pediatric population from the South-Southeast of Mexico that evaluated the AI.

Osteopontin (OPN) is a phosphoglycoprotein involved in bone remodelling, wound healing, cell adhesion, tissue remodelling, and immune response that is distributed widely in normal adult tissues. OPN biological activity is regulated by thrombin and matrix metalloproteinases (MMPs) cleavage, where the full-length (OPN-FL) protein and the cleaved OPN-N are associated with autoimmune diseases such as systemic lupus erythematosus (SLE). OPN overexpression has been associated with a predisposition to SLE and bad prognosis since OPN could mediate a sustained polyclonal B cell activation that besides to intracellular OPN (iOPN) form, promote the T follicular helper (T-FH) cells and enhance anti-nuclear antibody production. Currently, the role of OPN in lupus nephritis (LN) has been reported and extensively studied; however, no data are available about the potential mechanism of OPN in neuropsychiatric SLE (NPSLE). In this review, we highlighted the contribution of OPN and iOPN in LN and NPSLE immunopathology.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1((83-119),) D2, and B/B epitopes.

Objectives: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D1(83-119), D2, B/B, and B/B-COOH in co-vaccination with IFN-gamma or IL-10 in a murine model of lupus induced by pristane.

Material and methods: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D1(83-119), D2, B'/B, B'/B-COOH, IFN-gamma, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with S-35 and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-gamma from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy.

Results: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048).

Conclusion: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.

Objective: The aim was to establish if the balance adiponectin-oligomers, resolvin-E1 and chemerin levels could contribute to the insulin resistance (IR) setting of subjects with obesity, based on their serum levels and its relationship with inflammatory markers, metabolic profile and adiposopathy status.

Methods: This study included 230 individuals, classified according to World Health Organization criteria by body mass index (BMI) kg/m2 in two groups: without-obesity (from 18.5 to 29.9) and with-obesity (from 30.0 to 39.9). Body fat mass distribution, metabolic and inflammatory markers were measured by anthropometric, enzymatic and immuno-turbidimetry methods, respectively. Serum insulin, resolvin-E1, chemerin, and adiponectin-oligomers were evaluating by ELISA method. Analysis performed were correlations IR-indexes with adiposity, receiver operating characteristic (ROC) curves and the adiponectin-oligomers, resolvin-E1 and chemerin tertiles.

Results: Subjects’ with-obesity showed adiposopathy status, characterized by metabolic dysregulation and a subclinical inflammatory profile. They presented higher levels (`x ±SD, ng/mL) of resolvin-E1 (1227 ±668 versus 909 ±769, P= 0.017), chemerin (91 ±31 versus 79 ±23, P= 0.013) and LMW-Adiponectin (2257 ±797 versus 1030 ±1055, P= 0.011), whereas HMW-Adiponectin was lower (2470 ±1095 versus 3236 ±1848, P= 0.010), compared to the without-obesity individuals. Individuals’ with-obesity also displayed positive correlation of IR markers (rho from 0.163 to 0.479) along body fat measurements, metabolic and inflammation profiles. Moreover, a negative correlation of HMW-Adiponectin (rho from –0.564 to –0.214) with body fat measurements, metabolic and inflammation profiles. IR-indexes, LMW-Adiponectin and resolvin-E1/chemerin relationship showed differences between groups’ with-obesity and without-obesity, but not with gender. ROC curves shown potential ability of the LMW-Adiponectin levels to differentiate IR from non-IR individuals, with AUC of 0.815, P<0.0001 (95%, CI: 0.726-0.903).

Conclusion: The present study shown that LMW-Adiponectin-resolvinE1-chemerin serum unbalance establishes a specific relationship with adiposopathy in individuals with obesity, which could be a way to identify risk factors in early stages of IR.