Variant mannose-binding lectin alleles are associated with celiac disease

In this study, we investigated the role of mannose-binding lectin (MBL) in celiac disease, by performing genotype analysis for the three point mutations in the first exon of the gene in 117 Italian celiac patients (characterized by flat biopsy and positive for anti-endomysium antibody and human transglutaminase antibodies) and 130 pan-ethnic healthy controls. The frequency of homozygous mutant 0/ 0 was significantly higher in the 117 Italian celiac patients (0.13) than in the 130 pan-ethnic healthy controls (0.05; P=0.0405). An increased frequency of homozygous 0/0 allele was found among patients with celiac disease compared with controls. These results suggest an involvement of MBL in the pathophysiology of celiac disease.     

Anti Transglutaminase Antibodies Cause Ataxia in Mice

Background

Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.

Methods

We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.

Conclusion

The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.     

Vitamin D substrate–product relationship in idiopathic hypercalciuria

Absorptive hypercalciuria (AH) is associated with elevated levels of 1,25-dihydroxyvitamin D (1,25(OH)₂D). While no increase of 1,25(OH)₂D after oral administration of 25-hydroxyvitamin D (25OHD) at high doses has been claimed in normal subjects, a substrate–product relationship has been reported in normal children, young people after UV irradiation, older persons, postmenopausal women, primary hyperparathyroidism, renal failure, osteomalacia, and sarcoidosis. No data of this relationship in AH is available. To investigate 25OHD-1,25(OH)₂D substrate–product relationship in AH, 161 AH patients (mean age 60.9 ± 11.7 years) and 110 age- and sex-matched controls (mean age 61.5 ± 12.4 years) were studied. In 57 controls and 52 AH subjects 25OHD-1,25(OH)₂D relationship in basal conditions and after 2-week oral 25OHD (25 μg/day) administration were evaluated. In basal conditions 25OHD and 1,25(OH)₂D were correlated in both, controls and AH; 25OHD treatment was followed by an increase in serum 25OHD and 1,25(OH)₂D in both groups. However, delta responses of 25OHD and 1,25(OH)₂D to 25OHD were higher in AH suggesting an enhanced activity of 1α-hydroxylase. In conclusion, the higher response of 1,25(OH)₂D after oral 25OHD in AH patients suggests a differential capacity between both groups in handling the increases in 1,25(OH)₂D.     

Cost-effective HLA typing with tagging SNPs predicts celiac disease risk haplotypes in the Finnish, Hungarian, and Italian populations

Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy. The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95% to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk effects. The method is transferable between populations and therefore suited for large-scale research studies and screening of celiac disease among high-risk individuals or at the population level. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Lotta Koskinen and Jihane Romanos are authors with equal contribution.     

The analysis of the fine specificity of celiac disease antibodies using tissue transglutaminase fragments.

Celiac disease is an intestinal malabsorption characterized by an intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and an autoantigen located in the endomysium. The latter has been identified as the enzyme tissue transglutaminase which belongs to a family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. In a recent paper, we described the selection and characterization of anti-transglutaminase Igs from phage antibody libraries created from intestinal lymphocytes from celiac disease patients. In this work, using transglutaminase gene fragments, we identify a region of tissue transglutaminase recognized by these antibodies as being conformational and located in the core domain of the enzyme. This is identical to the region recognized by anti-transglutaminase Igs found in the serum of celiac disease patients.     

Short-term changes in zooplankton community in Paso Ancho basin (Strait of Magellan): functional trophic structure and diel vertical migration

Knowledge on community structure oriented to describe energy flow during late summer season in Paso Ancho basin (Strait of Magellan) is scarce and particularly affected by vertical diel migration (VDM). The main aim of this work is to identify the VDM patterns of selected species and functional feeding groups of mesozooplankton, collected by the electronic multinet BIONESS in 1995. Detailed studies were carried out on keystone components of the community: 7 species of copepods (Ctenocalanus citer, Drepanopus forcipatus, Metridia lucens, Clausocalanus brevipes, Scolecithricella minor, Paraeuchaeta antarctica, Calanus simillimus), one ostracod (Discoconchoecia elegans), one chaetognath (Sagitta tasmanica), one euphausiid (Euphausia vallentini), and two polychaetes (Pelagobia longicirrata, Tomopteris planktonis). Unexpected deviations from the classic pattern reported in literature were uncovered. The shallow layer mesozooplankton at night, although dominated by exclusively or preferentially herbivores, particularly by E. vallentini, was not represented by several species known as herbivores that remained in the deep layer throughout the day cycle. The deep-layer zooplankton throughout the day cycle was well represented by carnivores, detritivores, and omnivores. It is suggested that during low-chlorophyll summer conditions, the composition of functional groups and diet, and VDM patterns changed to take advantage of sinking phytoplankton and picoplankton in deep layers. Pelagic-benthic coupling would be strengthened due to animals that suppressed their vertical daily rise to the shallow layer at nights but remained in the deep layers to feed on a rain of particulate organic matter and other non-migrant zooplankton.     

Cardiac risk and MCNP/SISCODES doses in RT of the left internal mammary chain with photon and electron portals

Aim

The present study evaluated the increment of cardiac risk (CR) and absorbed dose in radiotherapy of the internal mammary chain (IMC), in particular with photon portals of 4 6?MV, and cobalt therapy (Co60); and, electron portals of 8, 12 and 16?MeV applied in the left breast, considering the adoption of a combined photon (16?Gy) and electron (30?Gy) protocols.

Helicobacter pylori and smoking: two additive risk factors for organic dyspepsia.

The hopes to distinguish between organic and functional dyspepsia on the grounds of the patient's symptomatology have not been fulfilled due to the low specificity of the so-called sinister symptoms. There is increasing evidence accumulating that Helicobacter pylori status and other environmental factors such as smoking have a higher discriminant power. Studies performed in our laboratories testing H. pylori status on gastric biopsy samples have shown that preselection of patients according to smoking habits and H. pylori status has a higher potential in avoiding unnecessary endoscopies in primary care patients as compared to risk factors based on patient complaints. Out of a total population of 282 primary care patients, one out of 24 endoscopies revealed significant pathology such as peptic ulcer or reflux esophagitis in the non-smokers with a negative H. pylori status, but when both risk factors were positive, the percentage rose to one out of every two patients. These observation have largely been confirmed by recent studies where H. pylori status was prospectively assessed prior to endoscopy by highly specific H. pylori serology or 13C breath test analysis.