Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns

Background: Whether antibodies directed to β2-Glycoprotein I (aβ2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. Objective: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aβ2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. Patients/methods: A comparison of patients with LA without (LA+/aβ2GPI−) and those with (LA+/aβ2GPI+) associated aβ2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aβ2GPI-. Results and conclusions: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aβ2GPI− patients were positive for aPS/PT antibodies. LA+/aβ2GPI− compared to 33 LA+/aβ2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aβ2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic event

A common ancestor more than 10,000 years old for patients with R854Q-related type 2N von Willebrand disease in Italy

Background. The impaired capacity of von Willebrand factor to carry factor VIII is identified as type 2N von Willebrand disease. R854Q is the most common type 2N mutation, and almost the only one identified in Italy. Design and methods. This study aimed to ascertain whether R854Q mutations in an Italian cohort of type 2N von Willebrand disease patients originated from single or recurrent events. Thirteen unrelated Italian families were investigated, analyzing the von Willebrand factor gene haplotype associated with the R854Q mutation. Results. A common haplotype emerged in all the families, extending from single nucleotide polymorphisms rs2166902 to rs216293 over 48.2 kb and including five intragenic markers. This haplotype is infrequent in the healthy Italian population (17% vs 100%, p<0.0001) and each genetic marker within said haplotype is similarly rare. These data strongly suggest a founder effect, supporting the existence of a single R854Q mutation event in our cohort of type 2N von Willebrand disease patients. Using the DMLE+ software and the Bengtsson and Thomson mathematical method, it was estimated that the R854Q mutation occurred from 10,000 to 40,000 years ago, which is consistent with the short dimension of the haplotype shared by our patients. Conclusions. Together with the fact that the R854Q mutation seems to be limited to the Caucasian populations, these findings suggest that a single mutational event took place after human populations moved from Africa towards Europe

New insight into the hypercoagulability of Cushing's syndrome.

BACKGROUND: Hypercoagulability and a tendency for thromboembolic complications are reported in Cushing's syndrome (CS). The hypercoagulability is due mainly to the cortisol-induced increase in von Willebrand factor (VWF) and factor VIII. This is not a constant feature of CS, however; it depends on particular single nucleotide polymorphism (SNP) haplotypes in the VWF gene promoter: haplotype 1 (-3268G/-2709C/-2661A/-2527G) confers a greater risk of VWF upregulation by cortisol than haplotype 2 (-3268C/ -2709T/-2661G/-2527A). In healthy individuals these SNPs are in linkage disequilibrium with the -2144 (GT)(n) of the VWF promoter: haplotype 1 mainly segregates with short GT repeats (15-19, GTs), haplotype 2 with long repeats (GT ≥ 20, GT(L)). METHODS: We analyzed the (GT)(n) locus, the SNP haplotypes and their association with VWF levels in 80 CS patients in order to precisely define the cortisol-sensitive VWF promoter pattern. CS patients were divided into groups A (increased VWF) and B (normal VWF). RESULTS: Haplotype 1 and (GT)(S) were more frequent in group A patients, and conferred a 9- and 7.5-fold risk of developing high VWF levels, respectively. Haplotype 2 and (GT)(L) were more represented in group B. There was also an unexpected higher prevalence of recombinant SNP haplotypes in CS patients (6.2%) than in normals (0.9%), p = 0.002. CONCLUSIONS: Our results indicate that the cortisol-induced increase in VWF may be predicted by VWF promoter polymorphisms, haplotype 1 and (GT)(S) being the sensitive pattern. These represent new markers for defining the prothrombotic risk of CS. The clinical significance, if any, of the increased recombination rate in SNP haplotypes in the VWF promoter warrants further study

Structure of arboreal and herbaceous strata in a neotropical seasonally flooded monodominant savanna of Tabebuia aurea

Large areas in the Pantanal wetland are covered by monodominant formations, e.g. typical landscapes with local names such as “paratudal”, dominated by T. aurea. Studies on structure of these formations generally include only woody strata, consequently the species richness registered is usually low due to the absence of the ‘ground layer’ of herbaceous and others low species. We recorded 13 species, 12 genera and 11 families for the arboreal stratum. Considering arboreal flora without the dominant (T. aurea) individuals showed great establishment in relation to the flood level between 35 – 45 cm while the individuals of the dominant species of 30 – 45 cm. The diameter distribution revealed that the population of T. aurea did not show the reverse J curve, the usual pattern for species in constant regeneration, also evidenced in inconstant Licourt quotient, indicating an episodic recruitment that could lead to future changes in structure. In the herbaceous strata we recorded 78 species, included in 62 genera and 27 families. Using plots method we sampled 46 species, 40 genera and 22 families, while in line interception we found 65 species distributed in 57 genera and 26 families. The floristic similarity of Sørensen between both methods was 59.4%, with 33 species in common, and the method of line interception was more efficient in detecting richness, with 35% more species found in the same time. According to the methods of plots and line interception applied on the woody stratum, our results gave similar detailed information on the structure of this type of savanna, and in spite of being monodominant it shows high species richness when the herbaceous stratum is taken into account. Plots and line interception methods showed similar results for the woody stratum and high species richness of the herbaceous stratum