bluuebunny/crossref_metadata_2025_split huggingface dataset:
High levels of IgM against methylglyoxal‐modified apolipoprotein B100 are associated with less coronary artery calcification in patients with type 2 diabetes
Authors: Engelbertsen D. , Anand D. V. , Fredrikson G. N. , Hopkins D. , Corder R. , Shah P. K. , Lahiri A. , Nilsson J. , Bengtsson E. 
Published: June 2011

Abstract.  Engelbertsen D, Anand DV, Fredrikson GN, Hopkins D, Corder R, Shah PK, Lahiri A, Nilsson J, Bengtsson E (Skåne University Hospital, Lund University, Malmö, Sweden; Cardiac Imaging and Research Centre, Wellington Hospital, London, UK; Malmö University, Malmö, Sweden; King’s College Hospital, London, UK; William Harvey Research Institute, London, UK; Cedars‐Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, UCLA School of Medicine, Los Angeles, CA, USA). High levels of IgM against methylglyoxal‐modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes. J Intern Med 2012; 271: 82–89.Objective.  Advanced glycation end products (AGE) have been implicated in diabetic vascular complications through activation of pro‐inflammatory genes. AGE‐modified proteins are also targeted by the immune system resulting in the generation of AGE‐specific autoantibodies, but the association of these immune responses with diabetic vasculopathy remains to be fully elucidated. The aim of this study was to determine whether antibodies against apolipoprotein B100 modified by methylglyoxal (MGO‐apoB100) are associated with coronary atherosclerosis in patients with type 2 diabetes.Methods.  We measured antibodies against MGO‐apoB100 in plasma from 497 type 2 diabetic patients without clinical signs of cardiovascular disease. Severity of coronary disease was assessed as coronary artery calcium (CAC) imaging. Immunoglobulin (Ig)M and IgG levels recognizing MGO‐apoB100 were determined by enzyme‐linked immunosorbent assay.Results.  Anti‐MGO‐apoB100 IgM antibody levels were higher in subjects with a low to moderate CAC score (≤400 Agatston units) than in subjects with a high score (>400 Agatston units; 136.8 ± 4.4 vs. 101.6 ± 7.4 arbitrary units (AU), P < 0.0001) and in subjects demonstrating no progression of CAC during 30 months of follow‐up (136.4 ± 5.7 vs. 113.9 ± 6.2 AU in subjects with progression, P < 0.0001). Subjects with a family history of premature myocardial infarction had lower levels of anti‐MGO‐apoB100 IgM. Female subjects had higher levels of anti‐MGO‐apoB100 antibodies and lower CAC than men. Accordingly, high levels of IgM against MGO‐apoB100 are associated with less severe and a lower risk of progression of coronary disease in subjects with type 2 diabetes.Conclusions.  Although conclusions regarding causal relationships based on epidemiological observations need to be made with caution, our findings suggest the possibility that anti‐MGO‐apoB100 IgM may be protective in diabetic vasculopathy.
Heritability not missing—genetic basis of sexual weaponry uncovered
Authors: SCOTT McCAIRNS R. J. , MERILÄ JUHA 
Published: June 2011

The chase to uncover the genetic underpinnings of quantitative traits of ecological and evolutionary importance has been on for a good while. However, the potential power of genome‐wide association studies (GWAS) as an approach to identify genes of interest in wild animal populations has remained untapped. Setting technical and economic explanations aside, the sobering lack of success in human GWAS might have fed this restraint. Namely, while GWAS have successfully identified genetic variants associated with hundreds of complex traits (e.g. Ku et al. 2010), these variants have generally captured only a low percentage of variance in traits known to be highly heritable—an observation came to be known as the ‘missing heritability’ (Maher 2008; Aulchenko et al. 2009). Hence, if the vastly resourced human studies have been unsuccessful (but see: Yang et al. 2010), why should we expect that less resourced studies of wild animal populations would be able do better? In this issue of Molecular Ecology, Johnston et al. (2011) prove this line of thinking wrong. In an impressive and what may well be the most advanced gene mapping study ever performed in a wild population, they identify a single locus (RXFP2) responsible for explaining horn phenotype in feral domestic sheep from St Kilda (Fig. 1). This same locus is also shown to account for up to 76% of additive genetic variance in horn size in male sheep: this contrasts sharply with most human GWAS where mapped loci explain only a modest proportion of genetic variation in a given trait. The Soay sheep of the St Kilda archipelago are a primitive feral breed of domestic sheep. Pictured are a male with vestigial horns (=‘scurred’; left) and two normal‐horned males (centre and right). Photograph courtesy of Peter Korsten.image
The significance of environmental exposure on the progression of allergic diseases
Authors: Wahn U. 
Published: June 2011

To cite this article: Wahn U. The significance of environmental exposure on the progression of allergic diseases. Allergy 2011; 66 (Suppl. 95):7–9.AbstractIn addition to strong genetic influences on atopic sensitization and disease development in infancy and childhood, a number of environmental factors modulate clinical and immunological phenotypes early in life and even prenatally. These factors include gastrointestinal or skin exposure to food allergens; respiratory exposure to indoor and outdoor allergens; presence of environmental pollutants such as tobacco smoke; and exposure to microbial compounds.
Allergic diseases, gene–environment interactions
Authors: Renz H. , Conrad M. , Brand S. , Teich R. , Garn H. , Pfefferle P. I. 
Published: June 2011

To cite this article: Renz H, Conrad M, Brand S, Teich R, Garn H, Pfefferle PI. Allergic diseases, gene–environment interactions. Allergy 2011; 66 (Suppl. 95): 10–12.AbstractAllergic asthma develops in part from dysregulation of the innate and adaptive immune functions, particularly an imbalance in the Th2‐driven adaptive immune response. This dysregulation is the result of complex interactions between genes and environment. These interactions occur both pre‐ and postnatally, providing opportunities for early interventions in immunological programming.
Allergen structures and epitopes
Authors: Meno K. H. 
Published: June 2011

To cite this article: Meno KH. Allergen structures and epitopes. Allergy 2011; 66 (Suppl. 95): 19–21.AbstractHuman type 1 hypersensitivity diseases such as allergic rhinoconjunctivitis are characterized by allergen‐specific IgE antibodies produced in allergic individuals after allergen exposure. IgE antibodies bound to receptors on the surface of effector cells trigger an allergic response by interacting with three‐dimensional (conformational) epitopes on the allergen surface. Crystal structures are available for complexes of antibody specifically bound to five allergens, from birch pollen, bee venom, cockroach, cow’s milk and timothy grass pollen. The details of the antibody–allergen interaction extending all the way to atomic resolution are available from such complexes. In vitro investigations using recombinant monoclonal antibodies and human basophils show that binding affinity is a key to triggering the allergic response. Continued molecular characterization of antibody–allergen interactions is paving the way for the use of recombinant allergens in allergen‐specific diagnosis and immunotherapy.
Mucosal dendritic cells in allergy and immunotherapy
Authors: Novak N. , Allam J.‐P. 
Published: June 2011

To cite this article: Novak N, Allam J‐P. Mucosal dendritic cells in allergy and immunotherapy. Allergy 2011; 66 (Suppl. 95): 22–24.AbstractThe oral epithelium contains oral mucosal Langerhans cells (oLCs) that constitutively express the high‐affinity IgE‐receptor FcεRI, the lipopolysaccharide receptor CD14 and toll‐like receptor (TLR)4. The distribution of oLCs profoundly differs at distinct oral mucosal sites, with higher numbers of oLCs detectable in the vestibulum compared with the sublingual region. The oLC response to activation of TLR4 and FcεRI and to binding of allergen suggests that these cells are involved in the maintenance of tolerance towards bacterial components and allergens. Thus, oLCs are important targets for allergens and adjuvants during sublingual immunotherapy, and characterizing them is crucial for improving allergen‐specific immunotherapy.
Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment
Authors: Bilò M. B. 
Published: June 2011

To cite this article: Bilò MB. Anaphylaxis caused by Hymenoptera stings: from epidemiology to treatment. Allergy 2011; 66 (Suppl. 95): 35–37.AbstractHymenoptera venom allergy occasionally causes fatal reactions. The prevalence of systemic reactions (SRs) is 0.3–8.9%, with anaphylaxis in 0.3–42.8% of cases. Factors contributing to reaction severity include older age, insect type, a previous less severe SR, preexisting diseases, concomitant treatments, mast cell diseases and elevated baseline tryptase serum concentration. Venom immunotherapy (VIT) is highly effective, as shown by sting challenge and spontaneous field stings. Indications for VIT are based on history of an SR, positive diagnostic tests, natural history and established risk factors for a severe outcome. Current strategies for reducing adverse reactions include anti‐IgE monoclonal antibody pretreatment, and purified aqueous and purified aluminium hydroxide adsorbed preparations. New strategies for VIT, mostly using recombinant allergen, are in development. Further improvements will increase the safety and efficacy of VIT.
Dosing and efficacy in specific immunotherapy
Authors: Demoly P. , Calderon M. A. 
Published: June 2011

To cite this article: Demoly P, Calderon MA. Dosing and efficacy in specific immunotherapy. Allergy 2011; 66 (Suppl. 95): 38–40.AbstractAllergen‐specific immunotherapy is used to treat allergic rhinoconjuctivitis and asthma worldwide. The clinical efficacy of the most common routes, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy, is documented for respiratory allergy by double‐blind, placebo‐controlled, randomised clinical trials (DB PC RCT). However, dose–effect relationships are not available for all extracts. The 1998 WHO Consensus Report on Allergen Immunotherapy found SCIT ineffective at low doses, with high doses more likely to result in an unacceptably high level of systemic reactions. Recent large well‐designed DB PC RCTs using SLIT grass pollen tablets have undergone phase II–III studies in adults with allergic rhinitis, yielding proper dose–response studies. These were analysed by the European Academy of Allergy and Clinical Immunology Immunotherapy Interest Group task force on dose effect. In general, low doses (5–7 μg of allergen Phl p 5 per day) are ineffective. Daily doses of 15–25 μg of the major allergen protein are required for significant clinical improvement measured by symptom scores. A higher dose (33–40 μg of Phl p 5 per day) was not more effective than 15–25 μg. Optimization of the allergen/adjuvant ratio may allow for lower allergen doses, increase the safety/efficacy profile and allow for shorter updosing. However, our analysis of the available studies concluded that every product requires its own dose–response relationship study.
Safety and tolerability of immunotherapy using various updosing schedules of a new SCIT product with an optimised allergen/aluminium hydroxide ratio
Authors: Jung K. 
Published: June 2011

To cite this article: Jung K. Safety and tolerability of immunotherapy using various updosing schedules of a new SCIT product with an optimised allergen/aluminium hydroxide ratio. Allergy 2011; 66 (Suppl. 95): 41–43.AbstractAllergen extracts for subcutaneous specific immunotherapy (SCIT) may be adsorbed to aluminium hydroxide for adjuvant effect and to delay allergen discharge. A product with an optimised allergen‐to‐aluminium hydroxide ratio enables a lower allergen dose and shorter introduction phase. The new therapeutic product Avanz (ALK, Denmark) has an optimised allergen‐to‐aluminium hydroxide ratio. A multicentre, randomised, phase II clinical trial evaluated the immunological effects and tolerability of two different five‐step updosing schedules for Avanz in 400 patients with grass pollen‐induced rhinoconjunctivitis with or without asthma, randomised into two groups. Group 1 were administered weekly, and group 2 were administered every 3 to 4 days. After updosing, patients received two maintenance injections after 2 and 4 weeks. In the updosing phase, local and systemic reactions were significantly more frequent in group 2 than group 1. In the maintenance phase, adverse reactions were less common in both groups. No generalised reactions with hypotension or fatal reactions occurred. An increase in allergen‐specific immunoglobulin G4 (IgG4) and IgE antibodies was established one week after the last injection. Avanz is a SCIT product with an optimised allergen‐to‐aluminium hydroxide ratio that enables a shorter updosing phase. We established an improved safety profile with weekly updosing compared with 3–4‐day intervals. Clinical trials are needed to confirm clinical efficacy.
Immunological measures as potential markers of dose
Authors: Kleine‐Tebbe J. 
Published: June 2011

To cite this article: Kleine‐Tebbe J. Immunological measures as potential markers of dose. Allergy 2011; 66 (Suppl. 95): 44–46.AbstractSpecific immunotherapy (SIT) induces immunological changes leading to a decrease in allergen‐driven symptoms and medication use. However, the use of arbitrary and variable assay formats and units hampers comparisons between SIT studies. The magnitude of IgG response induced by SIT is not directly linked to clinical improvement, so an increase in allergen‐specific IgG4 should be considered a necessary but not sufficient marker of clinical efficacy. Dose‐dependent IgG4 immune responses should be demonstrated by the manufacturer, not by doctors. Symptom and medication scores are essential end‐points for immunotherapy studies, but are subjective, so close association with objective assay measurements will be difficult. Nonetheless, blocking antibody assays combining serology and cellular function may provide a solution for relating immunological assay measurements to clinical outcomes.
Effect of AIT in children including potential to prevent the development of asthma
Authors: Valovirta E. 
Published: June 2011

To cite this article: Valovirta E. Effect of AIT in children including potential to prevent the development of asthma. Allergy 2011; 66 (Suppl. 95): 53–54.AbstractAllergy specific immunotherapy may alter the natural course of allergic disease. Thus, it is of significant importance, particularly in paediatric populations. Four studies using the grass allergy immunotherapy tablet (AIT) for allergic rhinoconjunctivitis in children showed good clinical outcomes and good safety profiles. Allergic rhinoconjunctivitis often precedes asthma, and treatment with specific immunotherapy has the potential to reduce the development of asthma in children suffering from rhinoconjunctivitis. Since Grazax® AIT has been shown to induce disease modification the prevention of asthma might be hypothesised. The GAP (Grazax® Asthma Prevention) trial is investigating the asthma preventive effect of standardised grass AIT in grass allergic children with rhinoconjunctivitis without asthma. The trial is a 5‐year, multicentre, multinational, randomised, double‐blind, placebo‐controlled, prospective trial for children aged 5–12 years. In a few years, the results will show if grass AIT with Grazax® can prevent the development of asthma in children suffering from allergic rhinoconjunctivitis.
Immunotherapy concepts under investigation
Authors: Kündig T. M. 
Published: June 2011

To cite this article: Kündig TM. Immunotherapy concepts under investigation. Allergy 2011; 66 (Suppl. 95): 60–62.AbstractAllergen‐specific immunotherapy (SIT) is effective, but used by only 5% of allergy patients, partly because it requires several years. Intralymphatic immunotherapy (ILIT) administers allergen directly into a subcutaneous lymph node and requires only three injections and a lower allergen dose than subcutaneous administration. ILIT was further improved using a recombinant allergen with enhanced uptake and decreased degradation by antigen‐presenting cells. Another interesting route is transcutaneous/epicutaneous immunotherapy (TCIT, EPIT), which administers allergen by a skin patch. Clinical trials show that TCIT, EPIT is safe and comparably effective to conventional immunotherapy. Implementation of these new methods would increase the spectrum of SIT options, allowing greater individual choice of SIT.
Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations
Authors: Akawi NA , Al‐Gazali L , Ali BR 
Published: June 2011

Akawi NA, Al‐Gazali L, Ali BR. Clinical and molecular analysis of UAE fibrochondrogenesis patients expands the phenotype and reveals two COL11A1 homozygous null mutations.Fibrochondrogenesis is documented to be a neonatally lethal rare recessively inherited disorder characterized by short‐limbed skeletal dysplasia. Here we report two patients from two unrelated consanguineous Emirati families who have unexpectedly survived till the ages of 3 and 6 years. These patients show additional symptoms which include developmental delay, profound sensory–neural deafness, severe myopia and progressive severe skeletal abnormalities. Linkage of fibrochondrogenesis in the Emirati families to chromosome 1 has been established using homozygosity mapping confirming recent findings by Tompson et al. in 2010. Screening of the COL11A1 gene revealed two null homozygous mutations [c.4084C>T (p.R1362X) and c.3708+437T>G] in the aforementioned two families. The c.4084C>T mutation is predicted to introduce a stop codon at position Arg1362, whereas the c.3708+437T>G mutation causes the activation of an intronic pseudoexon between exons 48 and 49. This resulted in the insertion of 50 nucleotides into the mRNA. The carriers of these mutations display ocular defects with normal hearing. In conclusion, our data shall improve the overall understanding of fibrochondrogenesis especially in surviving homozygous patients and, at least partly, explain the phenotypic variability associated with COL11A1 gene mutations.
A case of progressive thrombotic microangiopathy after ABO‐incompatible renal transplantation
Authors: Miura Masayoshi , Fujita Hiromi , Suzuki Akira , Kubota Kanako C. , Fukasawa Yuichiro , Shimoda Naohiko , Tsuchihashi Seiichiro , Tamaki Tohru 
Published: June 2011

Miura M, Fujita H, Suzuki A, Kubota KC, Fukasawa Y, Shimoda N, Tsuchihashi S, Tamaki T. A case of progressive thrombotic microangiopathy after ABO‐incompatible renal transplantation. Clin Transplant 2011: 25 (Suppl. 23): 19–22. © 2011 John Wiley & Sons A/S.Abstract:  A 21‐yr‐old man of blood type O receiving hemodialysis for IgA nephropathy underwent living‐related ABO‐incompatible (ABOI) renal transplantation from his mother, whose blood type is A. He was negative for flow cross‐match, anti‐human leukocyte antigen (HLA) antibody, and anti‐MICA antibody. Pre‐treatment anti‐A IgG titer was 1:256. Desensitization consisted of tacrolimus, mycophenolate mofetil, methylprednisolone, rituximab, and plasmapheresis. He developed acute antibody rejection at day 2 post‐transplant, which was successfully treated. After renal artery reconstruction surgery at day 91 for renovascular hypertension caused by renal artery stricture, the patient suffered from acute prostatitis, which subsequently induced type III acute antibody‐mediated rejection. Even after recovery from the rejection after temporary hemodialysis, graft function progressively deteriorated and consecutive allograft biopsy showed progressive thrombotic microangiopathy (TMA) without any evidence of donor‐specific antibody other than anti‐A antibody. The tacrolimus dose was kept low for fear of tacrolimus‐induced TMA. Despite these efforts, the patient resumed hemodialysis six months’ post‐transplant.
A case of recurrent focal segmental glomerulosclerosis (FSGS) involving massive proteinuria (>50 g/day) immediately after renal transplantation
Authors: Okamoto Masahiko , Koshino Katsuhiro , Sakai Kazuki , Nobori Shuji , Matsuyama Masahide , Ushigome Hidetaka , Okajima Hideaki , Masuzawa Naoko , Yoshimura Norio 
Published: June 2011

Okamoto M, Koshino K, Sakai K, Nobori S, Matsuyama M, Ushigome H, Okajima H, Masuzawa N, Yoshimura N. A case of recurrent focal segmental glomerulosclerosis (FSGS) involving massive proteinuria (>50 g/d) immediately after renal transplantation. Clin Transplant 2011: 25 (Suppl. 23): 53–58. © 2011 John Wiley & Sons A/S.Abstract:  A 15‐yr‐old girl with end‐stage kidney disease caused by primary focal segmental glomerulosclerosis (FSGS) underwent a living‐related donor kidney transplantation. The allograft functioned well immediately after reperfusion, but massive proteinuria exceeding 50 g/d appeared on day 3. Treatment with rituximab and plasma exchange (PE) successfully decreased the proteinuria to 10 g/d. A biopsy specimen on day 30 showed no segmental glomerulosclerosis but partial interstitial infiltration of inflammatory cells. An increased number of podocytes showed intracytoplasmic vacuolization, and an electron micrograph showed diffuse mild subendothelial edema and foot process effacement. The podocytes were hypertrophied but were not detached from the basement membrane. As the therapies used to reduce the patient’s proteinuria were having a limited effect, intravenous steroid pulse therapy followed by low‐density lipoprotein apheresis was performed. A biopsy specimen taken on day 120 showed no segmental glomerulosclerosis. Thrombus formation in one glomerulus and packed lymphocytes in the capillary loop of another glomerulus were detected. The patient’s clinical course was compatible with FSGS recurrence. Although the early pathological changes were not typical of FSGS, they might be indicative of the primary lesion that subsequently progresses to typical FSGS.