Clinical Characteristics of Patients With Acquired Partial Lipodystrophy: A Multicenter Retrospective Study.

BACKGROUND: Barraquer-Simons syndrome (BSS) is a rare, acquired form of lipodystrophy characterized by progressive loss of upper body subcutaneous fat, which affects face, upper limbs, and trunk. The pathogenesis of the disease is not entirely known and may involve autoimmune mechanisms. AIM: This study aimed to provide a comprehensive picture of the clinical, immunological, and metabolic features of a large cohort of patients with BSS. Our primary objectives included the validation of existing diagnostic tools, the evaluation of novel diagnostic approaches, and the exploration of potential disease triggers or genetic predispositions. SUBJECTS AND METHODS: Twenty-six patients were diagnosed with BSS based on accepted criteria defined by international guidelines. Anthropometric parameters, biochemical tests, organ- and non-organ-specific autoantibodies, HLA status, and screening of the LMNB2 gene were performed. RESULTS: Patients were predominantly females (73%); fat loss occurred mostly during childhood (77%) at a median age of 8 years. Among various anthropometric measures, the ratio between the proportion of fat mass in upper limbs and lower limbs showed the best predictive value for diagnosis. A total of 11.5% of patients had diabetes, 34.6% dyslipidemia, and 26.9% hepatic steatosis. Seventy-five percent of children and 50% of adults had C3 hypocomplementemia; 76% of patients were positive for 1 or more autoantibodies. HLA-DRB1 11:03 had higher allelic frequencies compared with the general population. A single variant in the LMNB2 gene was found in 1 patient. CONCLUSION: BSS has a childhood onset and is often associated with autoimmune diseases. Skinfold thickness measurements and fat assessment by dual energy X-ray absorptiometry are useful tools to identify the disease. C3 hypocomplementemia and the presence of autoantibodies may be used as additional diagnostic supportive criteria but the prevalence of C3 hypocomplementemia may be lower than previously reported.

Identification of a new HLA-DPB1 allele, HLA-DPB1*1485:01, in an Italian bone marrow donor.

The novel HLA class II allele HLA-DPB1*1485:01 is described.

Identification of the novel HLA-DPB1 allele, HLA-DPB1*1326:01, in an Italian bone marrow donor.

The novel HLA class II allele HLA-DPB1*1326:01 is described.

Correction to: Immunological features of patients affected by Barraquer-Simons syndrome.

Following the publication of the original article [1], the authors have requested to amend the Abstract and Discussion section as follows.

Immunological features of patients affected by Barraquer-Simons syndrome.

BACKGROUND: C3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells. RESULTS: C3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% in the general population). CONCLUSIONS: Our results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.

Identification of a novel HLA-DPB1, HLA-DPB1*687:01, in an Italian renal transplant candidate.

Two adjacent nucleotide substitutions in exon 2 characterize the novel class II HLA-DPB1*687:01 allele.

Oxygen Availability during Growth Modulates the Phytochemical Profile and the Chemo-Protective Properties of Spinach Juice.

Fruits and vegetables are a good source of potentially biologically active compounds. Their regular consumption in the human diet can help reduce the risk of developing chronic diseases such as cardiovascular diseases and cancer. Plants produce additional chemical substances when subject to abiotic stress or infected by microorganisms. The phytochemical profile of spinach leaves (Spinaciaoleracea L.), which is a vegetable with widely recognized health-promoting activity, has been affected by applying root hypoxic and re-oxygenation stress during plant growth. Leaf juice at different sampling times has been subject to liquid chromatography mass spectrometry (LC-MSn) analysis and tested on the human colorectal adenocarcinoma cell line HT29 by using the Comet assay. The cells were previously treated with H2O2 to simulate the presence of an oxidative stress (as in colon cancer condition) and the leaf juice application resulted in a significant antioxidant and protective in vitro effect. The duration of the hypoxic/re-oxygenation stress imposed on the plant reflects the antioxidant leaf juice content. After hypoxic stress (24 hours) and reoxygenation (2 hours), we show a decrease (50%) of the relative abundance of the principal identified antioxidant molecules but a higher antioxidant activity of the spinach juice on HT29 cells (20%). Data shows a complex relation between plant growing conditions and the modulation of secondary metabolites content in leaf juice that results in different chemo-protective activities in colon cancer cells.

Assessment of antioxidant and antiproliferative properties of spinach plants grown under low oxygen availability.

BACKGROUND: In the human diet, the consumption of fresh fruits and vegetables is important in maintaining good health and in preventing chronic diseases. It is known that plant-derived food is a powerful source of chemopreventive molecules, i.e. antioxidants, and spinach (Spinacia oleracea L., Chenopodiaceae) possesses a wide range of metabolites with such biological activity. Plant stress response could lead to the production of metabolites with high value for human health and this could be a tool to enhance the production of molecules with antioxidant activity in plants. RESULTS: Data reported in this paper confirm the antioxidant properties of spinach plants, and show a strong antiproliferative activity of leaf extract on HT-29 human cell line. Besides, the hypoxic stress seems to affect the pool of antioxidant molecules present in spinach leaves, as verified by means of HPLC-MS/MS analysis and the aluminium chloride and ABTS assays. CONCLUSION: Our findings represent a basis for improving the biological and pharmacological properties of spinach plants, including the use of different growth conditions to modulate the phytocomplex profile of spinach.

New insights into the metabolic and molecular mechanism of plant response to anaerobiosis.

Under anaerobic conditions, plants apply a wide spectrum of precise adaptive strategies responding to several critical challenges. The ability of efficiently sensing the oxygen presence demonstrates the existence of both direct and indirect ways of perception. The subsequent coordinate metabolic reassessment is currently under study. The complex molecular response implicates not only transcriptional and translational regulation of specific genes but also posttranscriptional and posttranslational regulatory mechanisms, each and all integrating the metabolic settings. Furthermore, the accumulation of typical metabolites during low oxygen stress condition is a key factor that suggests some critical topics in the regulation of metabolic pathways. Here, we summarize the main routes for adaptive behavior during oxygen depletion, from oxygen availability perception to recently discovered molecular mechanisms and metabolic adaptations.

New insights on plant cell elongation: a role for acetylcholine.

We investigated the effect of auxin and acetylcholine on the expression of the tomato expansin gene LeEXPA2, a specific expansin gene expressed in elongating tomato hypocotyl segments. Since auxin interferes with clathrin-mediated endocytosis, in order to regulate cellular and developmental responses we produced protoplasts from tomato elongating hypocotyls and followed the endocytotic marker, FM4-64, internalization in response to treatments. Tomato protoplasts were observed during auxin and acetylcholine treatments after transient expression of chimerical markers of volume-control related compartments such as vacuoles. Here we describe the contribution of auxin and acetylcholine to LeEXPA2 expression regulation and we support the hypothesis that a possible subcellular target of acetylcholine signal is the vesicular transport, shedding some light on the characterization of this small molecule as local mediator in the plant physiological response.

Evidence for the involvement of the Arabidopsis SEC24A in male transmission.

Eukaryotic cells use COPII-coated carriers for endoplasmic reticulum (ER)-to-Golgi protein transport. Selective cargo capture into ER-derived carriers is largely driven by the SEC24 component of the COPII coat. The Arabidopsis genome encodes three AtSEC24 genes with overlapping expression profiles but it is yet to be established whether the AtSEC24 proteins have overlapping roles in plant growth and development. Taking advantage of Arabidopsis thaliana as a model plant system for studying gene function in vivo, through reciprocal crosses, pollen characterization, and complementation tests, evidence is provided for a role for AtSEC24A in the male gametophyte. It is established that an AtSEC24A loss-of-function mutation is tolerated in the female gametophyte but that it causes defects in pollen leading to failure of male transmission of the AtSEC24A mutation. These data provide a characterization of plant SEC24 family in planta showing incompletely overlapping functions of the AtSEC24 isoforms. The results also attribute a novel role to SEC24 proteins in a multicellular model system, specifically in male fertility.

Cancer transmissibility across HLA barriers between immunocompetent individuals: rare but not impossible.

The axiom of human leukocyte incompatibility (HLA) incompatibility has always led scientists to consider cancer transmission between HLA-different individuals impossible. In fact, cancer transmission between individuals represents a frightening possibility in animal populations with limited HLA diversity or for rare cancers exploiting downregulation of HLA expression. We review here evidence from nonhuman models and settings for interhuman transmission.

COPII-mediated traffic in plants.

The secretory pathway encloses functionally interlinked organelles for the synthesis and deposition of most of the building blocks of eukaryotic cells, such as lipids, proteins and sugars. The coat protein complex II (COPII) is a specialized protein complex for the transport between secretory organelles, specifically from the endoplasmic reticulum (ER) to the Golgi apparatus. This review focuses on the developments on COPII research in the plant system. Here, we address the most recent advances in the distribution and regulation of ER-to-Golgi protein transport intermediates and functional analyses of COPII isoforms. New studies support that such isoforms might not be functionally redundant and that they might have unanticipated roles in maintaining the integrity of the ER.

Haplotype analysis of the H63D, IVS2+4t/c, and C282Y polymorphisms of the HFE gene reveals rare events of intragenic recombination.

OBJECTIVE: Two missense mutations of the HFE gene, one (C282Y) being a major gene for hereditary hemochromatosis and the other (H63D) playing a minor role in this disease, are carried by different haplotypes. Among other sequence variants of HFE, IVS2+4t/c polymorphism has been reported as a possible splicing mutation or risk modifier. Our aims were to identify sequence variants possibly associated with iron overload in our population, to study the intragenic haplotypes of the HFE gene, and to evaluate the role of IVS2+4t/c in hyperferritinemia. METHODS: We screened by direct sequencing the coding sequence and intron-exon boundaries of HFE in 265 patients with hyperferritinemia and 185 subjects from the general population. RESULTS: Linkage disequilibrium between the three pairs of polymorphic sites was complete between H63D and C282Y, whereas all four gametic types were present for both the H63D-IVS2+4t/c and the IVS2+4t/c-C282Y site pairs. The data supported a model in which the IVS2+4t/c polymorphism was ancestral, the D(63) mutation occurred on the t chromosome, and the Y(282) mutation occurred on the c chromosome; after the population spread of both mutations, intragenic recombination occurred on both sides of the t/c polymorphism, generating the rare haplotypes D(63)-c(IVS2+4)-C(282) and H(63)-t(IVS2+4)-Y(282). CONCLUSIONS: The IVS2+4c/t is a neutral polymorphism with regard to risk of iron overload. The presence of recombinant haplotypes on both its sides suggests a considerable evolutionary age of the two main risk alleles.