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Familial hypercholesterolemia (FH) features elevated oxidative stress and accelerated atherosclerosis driven by elevated levels of atherogenic lipoproteins relative to subnormal levels of atheroprotective high-density lipoprotein (HDL). Small, dense HDL3 potently protects low-density lipoprotein (LDL) against proinflammatory oxidative damage.To determine whether antioxidative and/or anti-inflammatory activities of HDL are defective in FH and whether such defects are corrected by LDL apheresis.Antioxidative and antiinflammatory activities of HDL were evaluated as protection of reference LDL from oxidative stress and capacity to prevent accumulation of proinflammatory oxidised lipids, respectively. Lipid surface rigidity of HDL was assessed using a fluorescent probe. HDL components were measured by analytical approaches. Systemic oxidative stress was characterized as plasma 8-isoprostanes.Pre-LDL-apheresis, FH patients (n = 10) exhibited elevated systemic oxidative stress (3.3-fold, P0.001) vs. sex- and age-matched normolipidemic controls (n = 10). Both antioxidative and antiinflammatory activity of HDL3 were impaired (up to -91%, P0.01) in FH. Sphingomyelin and saturated fatty acid contents were elevated in FH HDL3, resulting in enhanced lipid surface rigidity. The surface lipid content (phospholipids, free cholesterol) was reduced in FH (up to -15%, P0.001), whereas content of core lipids (cholesteryl esters, triglycerides) was elevated (up to +17%, P0.001). Molar apolipoprotein A-I content of HDL3 was subnormal in FH. A single LDL-apheresis session partially corrected (by up to 76%) deficient HDL antiatherogenic activities, attenuated systemic oxidative stress and partially normalised both the lipid composition and surface rigidity of HDL particles.FH features elevated oxidative stress and deficient antioxidative and anti-inflammatory activities of small, dense HDL3; such functional deficiency is intimately linked to anomalies in lipid and protein composition, which may impair the capacity of HDL to acquire and inactivate oxidized lipids.

Objectives Zinc transporter 8 (ZnT8) is specifically expressed in the pancreatic β-cell and is more restricted in its tissue distribution than other auto-antigens as glutamic acid decarboxylase 65 (GAD 65 ) and insulinoma-associated antigen-2 (IA2). ZnT8 autoantibodies (ZnT8A) assessment allows identifying rapid progression to clinical onset of the disease. We evaluated the prevalence of ZnT8A in adults of different ethnic and phenotypic groups and analyzed its potential utility as additional marker of autoimmunity in daily practice. Methods ZnT8A, GADA and IA2A were assessed using enzyme-linked immune-sorbent assay (ELISA) in 160 controls and 216 diabetic subjects. 105 were of type 1 diabetes (T1D), 17 had Latent Autoimmune Diabetes of Adults (LADA), 38 were type 2 diabetic (T2D) and 56 had ketosis-prone diabetes (KPD). 82 patients were newly diagnosed cases. Results ZnT8A were detected in 1% of controls and were not found in any of our 38 T2D subjects or 56 KPD subjects. In contrast, ZnT8A were detected in 18% of LADA subjects and in 38% of T1D subjects. A slight difference of percentage of ZnT8A positivity was found among our T1D ethnic groups. ZnT8A were positive in 41% of patients positive for GADA and 67% of patients positive for IA2A. The percentage of stratification achieved 91% when GADA, IA2A and ZnT8A were assessed simultaneously. Conclusions Results obtained for ZnT8A measurement using ELISA were consistent with previous data. Such investigation could improve the risk stratification and would be integrated in our daily practice.

Background and objective 1,25-dihydroxyvitamin D [1,25(OH)2D] is the most important vitamin D metabolite in regulating calcium and phosphorus metabolism and bone resorption. It is measured in plasma for diagnosis and management of patients with disorders influencing vitamin D metabolism. The most common methods for 1,25(OH)2D quantification are competitive isotopic I125 immunoassays. The purpose of this work is to compare the IDS isotopic immunoassay (IDS RIA) and the nonisotopic iSYS immunoassay (IDS iSYS) for 1,25(OH)2D measurement in human serum and in control samples obtained from the Vitamin D External Quality Assessment Scheme (DEQAS). Methods 1,25(OH)2D concentrations in 180 serum samples (87 females and 93 males) and in 25 samples from the DEQAS were assayed using IDS RIA and IDS iSYS methods. Both assays were performed after delipidation and immunoextraction steps. Measurement range was 9.0–348.0 pmol/L and 15.6–504.0 pmol/L for IDS RIA and IDS iSYS assay, respectively. ‘Normal adult’ reference ranges of 1,25(OH)2D were 43–168 pmol/L for IDS RIA and 63–228 pmol/L for IDS iSYS. Results The equation of the Deming regression analysis demonstrated that IDS iSYS tended to give lower 1,25(OH)2D concentrations by a mean of 20% over the tested concentration range when compared to IDS RIA. Both assays would easily meet the DEQAS goal of 80% of survey samples within 30% of the All-Laboratory Trimmed Mean “ALTM”. Results of 1,25(OH)2D obtained using IDS iSYS in samples distributed by DEQAS were closely related to those by LC–MS/MS method. Conclusions The concentrations of 1,25(OH)2D measured by the IDS iSYS tended to be lower than those of IDS RIA in patients, but quite comparable to those of LC–MS/MS and ALTM in DEQAS samples.

Objective— Absence of stearoyl-CoA desaturase-1 (SCD1) in mice reduces plasma triglycerides and provides protection from obesity and insulin resistance, which would be predicted to be associated with reduced susceptibility to atherosclerosis. The aim of this study was to determine the effect of SCD1 deficiency on atherosclerosis. Methods and Results— Despite an antiatherogenic metabolic profile, SCD1 deficiency increases atherosclerosis in hyperlipidemic low-density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Lesion area at the aortic root is significantly increased in males and females in two models of SCD1 deficiency. Inflammatory changes are evident in the skin of these mice, including increased intercellular adhesion molecule (ICAM)-1 and ulcerative dermatitis. Increases in ICAM-1 and interleukin-6 are also evident in plasma of SCD1-deficient mice. HDL particles demonstrate changes associated with inflammation, including decreased plasma apoA-II and apoA-I and paraoxonase-1 and increased plasma serum amyloid A. Lipopolysaccharide-induced inflammatory response and cholesterol efflux are not altered in SCD1-deficient macrophages. In addition, when SCD1 deficiency is limited to bone marrow–derived cells, lesion size is not altered in LDLR-deficient mice. Conclusions— These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics.