HLA class I and II diversity contributes to the etiologic heterogeneity of non-Hodgkin lymphoma subtypes

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma

A genome-wide association study of marginal zone lymphoma shows association to the HLA region

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10−15) and HLA-B (rs2922994, P=2.43 × 10−9) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Cross-linked chitosan/liposome hybrid system for the intestinal delivery of quercetin

Quercetin is a flavonoid with antioxidant/anti-inflammatory properties, poorly absorbed when administered orally. To increase its bioavailability and optimize its release in the intestine, a hybrid system made of liposomes coated with cross-linked chitosan, named TPP-chitosomes, was developed and characterized by light scattering, transmission electron microscopy, differential scanning calorimetry, X-ray powder diffraction and Turbiscan® technology. The TPP-chitosomes were nanosized (~180. nm), fairly spherical in shape and unilamellar. The actual coating of the surface of liposomes with the cross-linked chitosan was demonstrated by Small-Angle X-ray Scattering.The release of quercetin in simulated gastric and intestinal pH was investigated, the results showing that the system provided resistance to acidic conditions, and promoted the release in alkaline pH, mimicking the intestinal environment.The proposed hybrid system represents a promising combination of nanovesicles and chitosan for the delivery of quercetin to the intestine in the therapy of oxidative stress/inflammation related disorders

Particulate organic matter release below melting sea ice (Terra Nova Bay, Ross Sea, Antarctica): Possible relationships with zooplankton

Timing and rates of release of particulate organic matter (POM) beneath the Antarctic sea ice during the melting season are relatively unknown. To shed light on this topic, we investigated: i) quantity and biochemical composition of POM released below annual sea ice in Terra Nova Bay (TNB, Ross Sea, Antarctica) through sediment traps deployed at 10- and 30-m depth; ii) the abundance and taxonomic composition of phytoplankton; iii) the abundance and biochemical composition of two zooplankton species, namely the pteropods Clione limacina antarctica and Limacina helicina antarctica. Overall, our results show that in late spring-early summer in TNB the melting of annual sea ice determines a rapid release of particles into the underlying water column, and that those particles are transported downward at the rate of hours to days. POM fluxes were dominated by lipids, which probably resulted from zooplankton grazing activity on sea-ice algae and faecal pellets that were released into the water column. This, after the initial injection of particles, which were likely associated with sinking sympagic microalgal biomass derived from the sea ice melting, enhanced the nutritional value of POM. POM released beneath the sea ice, in turn, had a possible effect on the biochemical composition of the two pteropod species. Our results confirm that melting of sea ice in spring-summer each year in Antarctic coastal waters represents a fundamental step in the transfer of energy towards the higher trophic levels. Evidence of a decline in Antarctic sea ice over the last five years, plausibly as a consequence of global warming, underlines a conspicuous decline in habitat availability for sea-ice algae and, as a consequence, a drop in the availability of food for pteropods and the higher trophic levels of the coastal Antarctic Ocean

Trombocytopenic trombotica purpura (ttp) and metalloproteinase (mmp1). role for a possible proctetive effect

Background. Thrombocytopenic Trombotic purpura (TTP) is a rare disease. In TTP high concentration of multimeric factors cause platelet aggregations. The von willebrant factor (vwf) is a protein synthesized by endothelium and megakaryocytic is present in multimeric forms. Metalloproteinase are involved in cartilage proteolysis and participate in other processes of matrix cellular disruption. Objective. To evaluate polymorphism state in MMP1 (Matrix metalloproteinase-1) promoter gene in heterozygous or homozygous conditions and clinical correspondenceto TTP. Materials and methods. Forty-two consecutive cases with primary Thrombocytopenic trombotic purpura, median 42 year, range 43-82), 29 female, and 13 male were evaluated. DNA was collected from peripheral blood in mono nucleated cells. Saline method with small modification for DNA dried slides extraction was used. PCR method for transcript of a disintegrin and metalloprotease with thrombospondin type I domains 13(ADAMTS13) and beta actin controls were used. For study of MMP1 gene, polymorphism PCR method, and enzymatic ALU I digestions and agarose gel electrophoresis evaluation were used. Results were compared (case control analysis) to 150 (ratio 1:3.5) Sardinian control, matched for age, geographic zone and sex. Results. All transcripts for ADAMTS 13 were positive. The genotype analysis in patients groups (n=42) reveal 3/42 (7,1%) 2G/2G genotype, 25/42 (59.5%) 1G/2G , 14/42 (33,3%) 1G/1G. While in controls (n=150) were 50/150 (33.3%)2G/2G genotype, 66/150 (44.4%)1G/2G genotype, 33/150 (22.2%)1G/1G genotype respectively. Then, from 42/42 cases evaluation was evinced significative (X=7.5808, p=0.005). Respect control groups. On the basis of this observation the 2G/2G patient groups, we suppose a co-operative action between protheolitic activity of collagenase of MMP1 and reduced activity of ADAMTS 13. This could be originated from an increase of transcription activity of MMP1 with an increase of collagenase quantity. This 2G/2G genotype, could be s protective towards TTP disease. In addition and a prompt response to plasmapheresis did not present any relapse in 11,11, 8 years of continuous of follow-up respectively