Lewis Histo-Blood Group System and Associated Secretory Phenotypes

This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histoblood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual's Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone's Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis-negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis-positive individuals, the non-secretor genotype generates the Le(a+b–) phenotype, the secretor genotype causes the Le(a–b+) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.     

An account of the ticks of the northeastern of Spain (Acarina: Ixodidae).

The tick species commonly collected at the Northeast of Spain are reported in this paper. Data on hosts, temperature and humidity requirements, vegetation relationships, altitudinal distribution, and seasonal activity are included. R. sanguineus is commonly collected in areas with Mediterranean vegetation, esteppe, and semi-desertic esteppe, ranging from 190 to 1,000 meters above the sea level. R. sanguineus is related with sparse vegetal areas, and it is absent from areas with dense shrub or forests of every kind; sometimes, small populations may be collected in ecotones between Pinus spp. and esteppe formations. R. pusillus is closely related to areas of Mesomediterranean vegetation, sometimes subordinate to Pinus spp. and Quercus spp. The climate to which the species ally is always of continental type, with a hot and dry summer, and cold winter; although the species is commonly restricted to its main host, Oryctolagus cuniculus, several specimens have been collected from V. vulpes. Our data display the clear affinity of I. ricinus to the Supramediterranean vegetation (Aceri-Quercion faginae), places of Quercetum-Buxetum, as well as the Iberian Oromediterranean vegetation (Pinus sylvestris-Buxus sempervirens). Captures are scarce in forest of Fagus sylvatica, but data suggest that the species may be locally common on such places. Climate for the zones of collection of I. ricinus is Atlantic attenuated, with mild summers and humid winters. D. marginatus is strongly related to the xerophilic vegetation, widely spread through the Mediterranean, Supramediterranean, and hill levels, but does not colonize the true Oromediterranean vegetation. In our captures, the species is commonly collected in pubescent oak formations, but it does not penetrate in true forest associations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection and Characterization of Lewis Antigens in Plasma of Lewis-Negative Individuals Evidence of Chain Extension as a Result of Reduced Fucosyltransferase Competition

Nonacid plasma glycolipids from Lewis-negative individuals of nonsecretor, partial-secretor and secretor phenotypes were prepared and separated by thin-layer chromatography and immunostained with radiolabelled Lewis antibodies. Lewis-positive plasma and intestinal epithelial cell glycolipids from Caucasians representing the four recognized Lewis and secretor combined phenotypes were used as controls. By presenting these purified total glycolipids in a cell-free environment to Lewis antibodies we were able to demonstrate the presence of small amounts of Lewis antigens in Lewis-negative individuals. It is shown that lactotetraosylceramide and extended precursor glycolipids are present in all Le(a–b–) nonsecretors. Le^awas detected in 1 of the 3 Le(a–b–) nonsecretor plasmas and in the intestinal sample of the same phenotype. Lactotetraosylceramide was absent but H type 1 and Le^bwere both present in all group O Le(a–b–) secretors, and extended H type 1 reactive structures were also found in the partial secretor. These results clearly demonstrate that although the Lewis-negative phenotype exists at the serological level, this phenotype is not an 'all-or-nothing' phenomenon at the chemical level. We also show that in the presence of reduced fucosyltransferase activity, increased elongation of the precursor chain occurs, which allows us to postulate that fucosylation of the precursor prevents or at least markedly reduces chain elongation.     

The mentored clinical casebook project at Harvard Medical School.

An excellent physician must be aware of the countless issues that affect each patient's health. Many medical education programs expose students to a broad spectrum of disparate knowledge and hope they will integrate all the pieces into a coherent whole. The authors describe an explicit approach to integration used at Harvard Medical School since 2003 that aims to enhance students' learning in medical school and throughout their medical careers: the Mentored Clinical Casebook Project (MCCP). The MCCP is constructed on the premise that such integration does not occur suddenly but, rather, is an unending process. A first-year student is assigned to one clinician and follows one patient for one year. The student is expected to spend as much time with the patient as possible, in both clinical and nonclinical settings, seek help from the clinician, and consult other experts and sources to develop a complete picture of the patient's life. The student must produce a casebook that includes, but is not limited to, the patient's history; basic science, clinical, socioeconomic, and cultural issues; and self-reflection. The MCCP is intended to allow students to develop a deeper and more diverse understanding of what comprises a patient's health care life, to discern the patient as a person and the person as a patient. This educational project has been popular with students since its inception, providing them with a personal framework from which to address the needs of future patients and introducing them to how much they will continue to learn from their patients.     

Cellular expression and genetic control of ABH antigens in primary sensory neurons of marmoset, baboon and man

ABH antigens have been demonstrated in the posterior root ganglia (PRG) of 3 primate species (marmoset, baboon and man). Their expression corresponded to the ABO phenotype of the individual and was independent of the secretor gene. In marmosets more cells were positive for H (33 +/- 9%) than for A (19 +/- 6%). In baboons A or B antigens were more easily detected (66 +/- 9%) than the H antigens (48 +/- 5%). In humans more than two-thirds of PRG cells were positive for H but only a small proportion of these were positive for A or B. The ABH antigens were found mainly in the small and intermediate-size neurons whose central processes project to lamina II of the spinal cord posterior horn. Unipolar neurons of the Gasserian ganglion, neurons of the mesencephalic nucleus of the trigeminal nerve and of some visceral ganglia have also been shown to express these antigens which are also present in the fibre layer and glomeruli of the olfactory bulbs.     

Seasonal abundance of fleas (Siphonaptera: Pulicidae, Ceratophyllidae) on wild rabbits in a semiarid area of northeastern Spain

This paper reports the annual dynamics of wild rabbit fleas in a study site located in the Middle Ebro Valley, northeastern Spain. Fleas collected directly from wild rabbits included the species Spilopsyllus cuniculi (Dale), Xenopsylla cunicularis (Smit), Echidnophaga iberica (Ribeiro, Lucientes, Osácar, and Calvete), Caenopsylla laptevi (Beaucournu, Gil-Collado and Gilot), and Pulex irritans (L.). Monthly collections of adult and larval fleas made from within the first meter of selected burrow entrances also yielded fleas belonging to the same five species. Larval specimens of X. cunicularis, E. iberica, and C. laptevi were also found. Spilopsyllus cuniculi, a winter species that can only breed during the rabbit breeding season, was common on hosts from November to April. Xenopsylla cunicularis and E. iberica were summer species, whereas C. laptevi was abundant during the autumn and winter. Xenopsylla cunicularis and E. iberica larvae were found in burrows only during April and May, whereas those of C. laptevi were collected from October to January. The data suggested that X. cunicularis and E. iberica might diapause during the egg stage whereas C. laptevi diapauses during the pupal stage.     

Two myeloma globulins, IgG1-kappa and IgG1-lambda, from a single patient (Im). I. Purification and immunochemical characterization

Electrophoretic analysis of the serum from a patient Im suffering from a multiple myeloma revealed the existence of two abnormal bands. Purification of these two fractions on a DEAE—cellulose column showed that both fractions had the same sedimentation coefficient (7S), belonged to the same class (IgG), and subclass (γl) and bore the same allotype (Gm₁). However, the heavy (H) chains of one immunoglobulin were associated with type κ light (L) chains whereas those of the other were associated with type λ L chains.Three individual antigenic determinants were found in these two proteins. One was common to the H chains of both proteins and the other two were each specific to one of the L chains. These results suggest that the myeloma cells of patient (Im) were able to produce at least three polypeptide chains, one H chain and two different types of L chains.     

Soluble suppression of tumorigenicity-2 predicts pneumonia in patients with inhalation injury: Results of a pilot study

IntroductionSeveral mechanisms play a role in the development of pneumonia after inhalation injury. Our aim was to analyze whether higher concentrations of inflammatory markers or of biomarkers of epithelial injury are associated with a higher incidence of pneumonia in patients with inhalation injury.Material and methodsSecondary analysis of a single-center prospective observational cohort pilot study, performed over a two-year period (2015–2017) at the Burns Unit of the Plastic and Reconstructive Surgery Department of Vall d’Hebron University Hospital. All patients aged 18 with suspected inhalation injury undergoing admission to the Burns Unit were included. Plasma biomarkers of the lung epithelium (RAGE and SP-D), inflammation markers (IL6, IL8), and IL33, as well as soluble suppression of tumorigenicity-2 (sST2) levels, were measured within the first 24 h of admission.ResultsTwenty-four patients with inhalation injury were included. Eight (33.3%) developed pneumonia after a median of 7 (4–8) days of hospital stay. Patients with pneumonia presented higher plasma concentrations of sST2 (2853 [2356–3351] ng/mL vs 1352 [865–1839] ng/mL; p < 0.001), IL33 (1.95 [1.31–2.59] pg/mL vs 1.26 [1.07–1.45] pg/mL; p = 0.002) and IL8 (325.7 [221.6–430.0] pg/mL vs 174.1 [95.2–253.0] pg/mL; p = 0.017) on day 1 of inclusion. Plasma sST2 concentration in the first 24 h demonstrated excellent diagnostic accuracy for predicting the occurrence of pneumonia in patients with smoke inhalation (AUROC 0.929 [95%CI 0.818–1.000]). A cutoff point of ≥2825 ng/mL for sST2 had a sensitivity of 75% and a specificity of 100%. The risk ratio of pneumonia in patients with sST2 ≥ 2825 ng/mL was 7.14 ([95% CI 1.56–32.61]; p = 0.016).ConclusionsPlasma sST2 in the first 24 h of admission predicts the occurrence of pneumonia in patients with inhalation injury.     

Impact of donor extracellular vesicle release on recipient cell “cross-dressing” following clinical liver and kidney transplantation

In several murine models of transplantation, the “cross-dressing” of recipient antigen presenting cells (APCs) with intact donor major histocompatibility complex (MHC) derived from allograft-released small extracellular vesicles (sEVs) has been recently described as a key mechanism in eliciting and sustaining alloimmune responses. Investigation of these processes in clinical organ transplantation has, however, been hampered by the lack of sensitivity of conventional instruments and assays. We have employed advanced imaging flow cytometry (iFCM) to explore the kinetics of allograft sEV release and the extent to which donor sEVs might induce cross-dressing following liver and kidney transplantation. We report for the first time that recipient APC cross-dressing can be transiently detected in the circulation shortly after liver, but not kidney, transplantation in association with the release of HLA-bearing allograft-derived sEVs. In liver transplant recipients the majority of circulating cells exhibiting donor HLA are indeed cross-dressed cells and not passenger leukocytes. In keeping with experimental animal data, the downstream functional consequences of the transfer of circulating sEVs harvested from human transplant recipients varies depending on the type of transplant and time posttransplant. sEVs released shortly after liver, but not kidney, transplantation exhibit immunoinhibitory effects that could influence liver allograft immunogenicity.