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Showing posts with label Anaphylaxis. Show all posts

Monday, November 23, 2015

WHEAT GENOME PUZZLE / SECOND STAPLE IN FOOD ALLERGY, WORLDWIDE

Wheat Allergy as treated by Carlos E Mijares MD, former fellow in Allergy / Immunology, pediatrics at University of Kansas, USA.
Currently, practicing at www.centromedicodecaracas.com,ve
carlosmixares@gmail.com

Elimination Diet Sheet : Wheat, Oats, Rice, Barley, Rye. All breads and baked goods, flour, cake,crackers, doughnuts, cookies, waffles, pancakes, pretzels, icecream cones, pie crust, macaroons, rolls, buns, cereals, macaroni, spaghetti, noodles, gravy.

Common Food Relationships:
Family or Class     Important Members      Usual Manifestations                Cross reactivity

Buckwheat            Buckwheat, rhubarb      Rare offenders;                          Probably strong
                                                                    buckwheat useful
                                                                    in wheat-sensitive
children

Durum roll please: updated genome a huge milestone for designing high-yield sustainable wheat

The updated wheat genome sequence, released today, is a new step toward generating improved wheat varieties. Here, Genome Biology's Dominique Morneau outlines the challenges and opportunities that accompany the sequencing of the wheat genome.

Dominique Morneau 12 Nov 2015

Photo: The Genome Analysis Centre

Bread wheat (Triticum aestivum) is the second most highly produced cereal worldwide, grown on more than 215 million hectares, and the leading source of vegetable protein in human food. It was first domesticated in western Asia around 11,700 years ago, after which it spread to North Africa, Europe, and East Asia. Scientists are currently trying to figure out how to feed a growing population; in the next 50 years, we will need to grow more wheat than has been produced since the dawn of agriculture.
The key to improving wheat lies in identifying genes that can be exploited to meet the increased demand for high quality food. Unfortunately, sequencing the wheat genome is proving to be quite difficult.

The complexity of the wheat genome

Bread wheat is an allohexaploid, meaning that it has six sets of seven chromosomes derived from three different progenitor species (Triticum uratru, Aegilops speltoides, and Aegilops tauschii). The wheat genome is divided into three subgenomes: A, B, and D, each of which is almost twice as large as the human genome.
The wheat genome itself isn’t any harder to sequence than smaller genomes. What researchers have been struggling with is putting all the letters together in the right order. The wheat genome contains 17 gigabases (compared to the 3 gigabase human genome), and 80% of it is repetitive sequences. Using whole-genome shotgun sequencing methods thus becomes unattractive, since they generate reads of 500-1000 bases.
To understand why this problem is so complex, imagine a jigsaw puzzle with 17 million small pieces, 80% of which are very similar to each other. An international consortium of 1,100 researchers from 55 countries has been working on sequencing and assembling the wheat genome for the last 10 years!

The wheat genome – spelt out here

The wheat genome is currently being sequenced chromosome by chromosome. In July 2014, a draft of the full genome was published in the journal Science along with a reference sequence for chromosome 3B. Because of the complexity of the genome, the draft genome has lower accuracy, with segments either missing or in the wrong order or orientation.
Since then, work has focused on producing reference-quality assemblies for the remaining chromosomes – filling in the gaps with high accuracy and removing ambiguity in the order of segments – and mapping specific genes and genomic features. Other researchers have used the draft genome to study the evolution of wheat and other cereals, and to find variability in loci encoding agronomically important traits.
Today, The Genome Analysis Centre (TGAC) in Norwich, UK, has made a more complete and accurate wheat genome assembly available to the research community. The updated genome is now assembled into fewer, larger sections of DNA covering regions that were previously not sequenced. These regions include many of the large and complex groups of genes in wheat that contribute to the nutritional and bread-making quality of the grain.

wheat 2 — Photo: The Genome Analysis Centre

Flour power

Here at Genome Biology, we’re big fans of wheat genomics, and have put together a collection of articles that we’ve published in the last year. Highlights include a more in-depth understanding of the structure, evolution, and expression of genes from chromosome 3B, a new method for assembling the wheat genome, finding sequence variations across the genome, and identifying genes that produce important traits that we may want to exploit, like grain dormancy.
But there’s more to wheat genomics than meets the eye. Growing wheat also means dealing with a slew of pathogens that affect yield. As interest in wheat genomics grows, so too does work in pathogenomics to prevent productivity losses, like those caused by the wheat yellow rust pathogen (Puccinia striiformis f. sp. tritici).

Never miss a triticum

The updated wheat genome is another step toward a chromosome-based complete genome in this important crop species. With this information, plant breeders will have high quality tools at their disposal to identify specific genes affecting agronomically important traits, such as yield, grain size and weight, nutritional quality, and stress tolerance. This will enable farmers and breeders to produce new wheat varieties better adapted to increasing demand in a changing climate.

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Wednesday, September 30, 2015

WHAT IS NEW IN DERMATOLOGY 2015 ?

What's new in dermatology

Authors
Abena O Ofori, MD
Rosamaria Corona, MD, DSc

Disclosures: Abena O Ofori, MD Nothing to disclose. Rosamaria Corona, MD, DSc Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

Conflict of interest policy

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Aug 2015. | This topic last updated: Sep 24, 2015.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ACNE AND ROSACEA

Serum potassium monitoring during spironolactone therapy for acne (March 2015)

Spironolactone is an androgen receptor antagonist that is effective for the treatment of acne in females. Although periodic monitoring of serum potassium levels is often performed during treatment with spironolactone, there is uncertainty about the need for monitoring in young, healthy acne patients. A large retrospective study comparing the rate of hyperkalemia during treatment with spironolactone with baseline rates of hyperkalemia in women with acne (ages 18 to 45) did not find increased rates of hyperkalemia during spironolactone therapy, suggesting that periodic monitoring of serum potassium in healthy women is not necessary [1]. These results cannot be applied to patients who may be at increased risk for hyperkalemia due to heart failure, renal disease, concomitant medical therapy, or other conditions. (See "Hormonal therapy for women with acne vulgaris", section on 'Side effects'.)

ATOPIC DERMATITIS AND OTHER DERMATITIS

Acute worsening of atopic dermatitis due to aeroallergen exposure (July 2015)

Environmental allergens are a trigger of atopic dermatitis (AD) in a small subset of children and adults. Patients who have environmental allergies as a trigger of AD have persistent disease with chronic exposure to an allergen in the environment. A small study of adults with AD demonstrated that exposure to grass pollen in an environmental challenge chamber for two consecutive days resulted in a significant worsening of AD on exposed skin for the five days after challenge compared with exposure to clean air (placebo) [2]. This study shows that an isolated exposure to an aeroallergen can cause an acute flare of AD in sensitized individuals. (See "Role of allergy in atopic dermatitis (eczema)", section on 'Aeroallergens'.)

Pimecrolimus for atopic dermatitis in infants and young children (May 2015)

Topical calcineurin inhibitors have been approved in the United States as second-line therapies for the treatment of mild to moderate atopic dermatitis (AD) in adults and children ≥2 years. However, they have been used off-label as first-line treatment for AD in younger children and infants, in the absence of long-term studies evaluating their efficacy and safety. A five-year randomized, open-label trial evaluated the safety and long-term efficacy of pimecrolimus 1% cream compared with low or mid-potency topical corticosteroids in over 2400 infants with mild to moderate AD [3]. After five years, overall treatment success was achieved in approximately 90 percent of children in both groups. Growth, immune function, and cancer rates were similar in the two groups, as were overall rates of adverse events. However, episodes of bronchitis, infected eczema, impetigo, and nasopharyngitis were slightly more frequent in the pimecrolimus group, and the rates of cutaneous adverse events (eg, skin irritation, atrophy, telangiectasias) were not reported. Thus, the advantage of using pimecrolimus rather than low to mid-potency topical corticosteroids in this age group remains unclear. (See "Treatment of atopic dermatitis (eczema)", section on 'Off-label use in infants'.)

Unclear association between atopic dermatitis and lymphoma (May 2015)

The association between atopic dermatitis and lymphoma is controversial. A 2015 systematic review and meta-analysis of four cohort studies and 18 case-control studies found a modest increase in the risk of lymphoma in patients with atopic dermatitis compared with the general population [4]. The risk increase was significant in the meta-analysis of the cohort studies but not in the case-control studies. However, the large heterogeneity of case-control studies in study design and diagnostic criteria does not allow any definite conclusion. In particular, due to overlapping clinical features, cases of cutaneous T cell lymphoma may have been initially misdiagnosed and treated as severe atopic dermatitis. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Risk of lymphoma'.)

Depression and anxiety disorders in patients with atopic dermatitis (April 2015)

Several lines of evidence suggest that the incidence of psychiatric comorbidities, including major depression and anxiety disorders, is increased among patients with atopic dermatitis and may be influenced by factors such as perceived disease severity and quality of life. A longitudinal cohort study evaluated the risk of developing major depression or anxiety disorders later in life among more than 8000 adolescents and adults with atopic dermatitis and age- and sex-matched controls [5]. Patients with atopic dermatitis had a six- and fourfold increased risk of developing major depression or anxiety disorders, respectively. These findings suggest that the identification and treatment of psychiatric comorbidities are important aspects of the management of patients with atopic dermatitis. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Depression and anxiety disorder'.)

AUTOIMMUNE AND SYSTEMIC DISEASES

Benefit of long-term management on risk for vulvar carcinoma in women with vulvar lichen sclerosus (June 2015)

Vulvar lichen sclerosus is a chronic disease associated with an increased risk for vulvar carcinoma. The findings of a prospective cohort study of 507 women with vulvar lichen sclerosus suggest that topical corticosteroid therapy, used both to achieve disease control and for long-term maintenance treatment, may reduce cancer risk [6]. Women who reported consistent adherence to treatment instructions had a lower incidence of vulvar carcinoma or vulvar intraepithelial neoplasia than women who reported less consistent adherence (0 versus 4.7 percent). In addition, patients who adhered to treatment had better symptom control and reduced risk for vulvar scarring. These findings suggest that consistent treatment rather than an "as needed" approach to the long-term management of vulvar lichen sclerosus may improve patient outcomes. (See "Vulvar lichen sclerosus", section on 'Topical corticosteroids'.)

Effects of rituximab in systemic sclerosis (May 2015)

In patients with systemic sclerosis (SSc), B cell infiltration has been demonstrated within skin and lung biopsies. Earlier case reports suggested that B cell depletion could attenuate skin and lung fibrosis, and now a larger study of 63 SSc patients and 25 matched controls has evaluated the therapeutic effects of rituximab [7]. After a follow-up period of approximately seven months, patients treated with a single course of rituximab demonstrated a significant improvement in the modified Rodnan skin score (mRss). Among SSc patients with interstitial lung disease, rituximab also prevented a further decline in forced vital capacity compared with matched controls. There were no serious adverse events among rituximab-treated patients. However, this study had many limitations, and additional studies are needed to establish the long-term efficacy of rituximab for skin and lung fibrosis in systemic sclerosis before routine use can be recommended. (See "Immunomodulatory and antifibrotic approaches to the treatment of systemic sclerosis (scleroderma)", section on 'Rituxumab'.)

Apremilast for oral ulcers in Behçet’s disease (April 2015)

There remains a need for effective therapy for recurrent oral ulcers in patients with Behçet’s syndrome. Preliminary data suggest that apremilast, an orally administered phosphodiesterase-4 inhibitor known to modulate several inflammatory pathways, is beneficial in treating oral ulcers. A randomized, phase II trial including over 100 patients with Behçet’s syndrome found that patients who received apremilast had a significant reduction in the number of oral ulcers at 12 weeks, as compared with those in the placebo group [8]. There was also a significant reduction in pain from oral ulcers. Nausea, vomiting, and diarrhea were more common than in the placebo group, which is similar to findings seen in previous studies of apremilast for the treatment of psoriasis and psoriatic arthritis. Additional studies are needed to determine the long-term efficacy and safety of apremilast for oral ulcers before routine use can be recommended. (See "Treatment of Behçet’s syndrome", section on 'Oral aphthae and genital ulcers'.)

INFECTIONS AND INFESTATIONS

Updated recommendations for pediatric head lice (May 2015)

Pediculosis capitis is a common condition that can lead to physical discomfort and social stigmatization. An update to the 2010 clinical report on head lice published by the American Academy of Pediatrics incorporates new therapies (spinosad and topical ivermectin), clarifies diagnosis and treatment protocols, and provides guidance for the management of children with pediculosis capitis in the school setting [9]. Examples of major points in the update include recommendations that no child should be excluded from school because of head lice or nits and that pyrethroids remain reasonable first-line therapies for primary treatment of pediculosis capitis in communities where resistance to pyrethroids is unproven. (See "Pediculosis capitis", section on 'Pediculicide selection'.)

The efficacy of an inactivated vaccine to prevent zoster (April 2015)

The live attenuated zoster vaccine reduces the risk of herpes zoster with a reported vaccine efficacy of 60 to 70 percent in adults 50 years and older, but it cannot be used in immunocompromised individuals and may have decreased efficacy in adults 70 years and older. A randomized, placebo-controlled trial evaluated the efficacy of HZ/su, an experimental recombinant inactivated zoster vaccine administered in two doses two months apart, among 15,411 adults 50 years and older [10]. After three years of follow-up, the overall vaccine efficacy against herpes zoster was 97.2 percent (95% CI 93.7-99.0), and efficacy among adults 70 years and older was similar to that seen in adults between 50 and 69 years of age. (See "Prevention of varicella-zoster virus infection: Herpes zoster", section on 'Inactivated vaccines'.)

PEDIATRIC DERMATOLOGY

Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region [11]. All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)

PSORIASIS AND OTHER PAPULOSQUAMOUS DISORDERS

Secukinumab, an anti-IL17A antibody, for psoriatic arthritis (August 2015, MODIFIED August 2015)

Secukinumab, an anti-interleukin (IL)-17A antibody, is available for the treatment of psoriasis in the United States and other countries, and has been evaluated for psoriatic arthritis (PsA) using various routes of administration and dosing regimens. In a multicenter randomized trial, involving almost 400 patients with active PsA, secukinumab (300, 150, or 75 mg administered subcutaneously weekly for four weeks and every four weeks thereafter, consistent with the regimen for psoriasis) was superior to placebo in achieving significant improvement in joint and skin disease, and in physical function and quality of life [12]. Responses by weeks 12 to 16 were similar to those at week 24 (ACR20 responses of 54, 51, and 29 versus 15 percent), and benefit was sustained at 52 weeks. The drug was well-tolerated and may have a future role in the treatment of psoriatic arthritis. (See "Treatment of psoriatic arthritis", section on 'IL-17 blockade'.)

Comparative efficacy of secukinumab and ustekinumab for plaque psoriasis (July 2015)

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, is a highly effective new treatment for psoriasis that was superior to etanercept in earlier trials. In the first randomized trial to compare secukinumab with ustekinumab, another established psoriasis therapy, secukinumab was more effective than ustekinumab for moderate to severe plaque psoriasis [13]. Safety profiles for the two drugs were similar. The expanding literature on the comparative efficacy of psoriasis therapies will provide valuable information for therapeutic decision making. (See "Treatment of psoriasis", section on 'Secukinumab'.)

Phase III trial support for oral tofacitinib for plaque psoriasis (July 2015)

Oral therapy for psoriasis is advantageous because of the ease of administration compared with topical medications, injected or infused medications, and phototherapy. Tofacitinib, an oral janus kinase (JAK) inhibitor used for the treatment of rheumatoid arthritis, is under investigation for the treatment of psoriasis. A phase III trial that compared two different doses of tofacitinib with etanercept and placebo found that the higher dose of tofacitinib (10 mg twice daily) was superior to placebo and non-inferior to etanercept in the treatment of moderate to severe plaque psoriasis [14]. Other phase III randomized trials also support the efficacy of tofacitinib therapy [15]. Tofacitinib represents a potential addition to the armamentarium for psoriasis therapy. (See "Treatment of psoriasis", section on 'Future therapies'.)

Risk for vascular complications of diabetes in patients with psoriasis (June 2015)

Psoriasis may be associated with increased risk for vascular complications of diabetes. A retrospective cohort study that compared risk for microvascular and macrovascular complications in diabetic patients with psoriasis with risk for these complications in diabetic patients without psoriasis found a modest increase in risk for both types of complications in patients with psoriasis [16]. Additional study is needed to confirm these findings. (See "Comorbid disease in psoriasis", section on 'Implications'.)

SKIN CANCER

Sonidegib approved for advanced basal cell carcinoma (July 2015)

Targeted inhibition of the Hedgehog pathway has antitumor activity against advanced basal cell carcinoma. Based upon the results of a phase II trial [17], sonidegib was approved at a dose of 200 mg orally once a day by the US Food and Drug Administration for patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or who are not candidates for surgery or radiation therapy [18]. Sonidegib provides an additional treatment option for these patients. (See "Systemic treatment of advanced cutaneous squamous and basal cell carcinomas", section on 'Sonidegib'.)

Weak association between citrus fruit and melanoma (July 2015)

An analysis of data from over 100,000 individuals participating in the Nurse’s Health Study found a modest 36 percent increase in melanoma risk associated with high dietary intake of citrus fruit or juice, after adjusting for known risk factors for melanoma, such as family history of melanoma, phenotypic characteristics, number of nevi, and lifetime number of blistering sunburns [19]. A potential explanation for this association is that citrus fruits are a source of psoralens, chemical compounds present in plants known to be photosensitizers. However, the results of this study need further confirmation, because, given the small increase in risk, residual confounding cannot be excluded. In the meanwhile, changes in dietary advice to the public are not warranted. (See "Risk factors for the development of melanoma", section on 'Other proposed risk factors'.)

Melanoma incidence in the United States (June 2015)

A report from the Centers for Disease Control and Prevention indicates that melanoma incidence rates doubled in the United States over the three decades from 1982 to 2011, while the mortality rates remained constant over time [20]. The annual number of cases is expected to double over the next 15 years. Based upon findings from SunSmart, an Australian community-wide skin cancer prevention program designed to raise awareness, change personal behaviors, and influence institutional policy and practices, the report estimates that a comprehensive skin cancer prevention program in the United States could prevent 20 percent of melanoma cases between 2020 and 2030. (See "Risk factors for the development of melanoma", section on 'Incidence'.)

Topical 5-fluorouracil for the long-term control of actinic keratoses (May 2015)

Topical 5-fluorouracil (5-FU) is used as a field treatment in patients with multiple actinic keratoses (AKs) and may be effective for the long-term control of AKs. In a randomized trial, 932 participants with multiple AKs on the face and ears were treated with 5% 5-FU cream or vehicle twice daily for four weeks and followed-up for an average time of 2.6 years [21]. Compared with the control group, patients in the 5-FU group had a significantly higher rate of complete clearance at six months and fewer AKs at 42 months. (See "Treatment of actinic keratosis", section on 'Topical 5-fluorouracil'.)

SURGICAL AND COSMETIC DERMATOLOGY

Effect of needle diameter on patient discomfort during facial injection of botulinum toxin (September 2015)

Although previous data on the impact of injection needle diameter on patient discomfort has been equivocal, studies evaluating this issue have had various methodological flaws. A small randomized trial designed to minimize such flaws found that patients receiving facial injections of botulinum toxin A for forehead wrinkles were less likely to experience clinically significant pain when injected with a 32-gauge needle than with a 30-gauge needle [22]. This finding suggests that use of a smaller diameter needle may benefit patients who experience significant pain during facial injections. (See "Overview of botulinum toxin for cosmetic indications", section on 'During treatment'.)

Cyanoacrylate glue for the ablation of incompetent superficial veins (March 2015)

Several methods are available for the ablation of incompetent superficial veins. A system that ablates the treated vein using a cyanoacrylate adhesive agent has been approved for use in the United States [23]. The procedure is performed like radiofrequency and laser ablation, but without the need for tumescent anesthesia. In a randomized trial comparing this system with radiofrequency ablation, short-term outcomes at three months were similar [24]. Longer term follow-up is needed to determine the durability of the results. (See "Liquid, foam, and glue sclerotherapy techniques for the treatment of lower extremity veins", section on 'Cyanoacrylate glue'.)

OTHER DERMATOLOGY

Afamelanotide for protoporphyria (August 2015)

Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are cutaneous porphyrias that present in childhood with painful, non-blistering photosensitivity within minutes of sun exposure. Affected individuals must avoid sunlight, often with substantial reduction in their quality of life. Afamelanotide is a new therapy for EPP and XLP that is administered as a subcutaneous implant every other month. The mechanism involves increased melanin production; there are no effects on porphyrin levels. Two multicenter randomized trials in adults with EPP or XLP (168 patients total) found that afamelanotide substantially reduced photosensitivity and improved sunlight tolerance, with minimal toxicities [25]. Thus, for adults with EPP or XLP, we suggest afamelanotide. This therapy is available in Europe but not in the United States. Dosing and safety data in children have not been reported. (See "Erythropoietic protoporphyria and X-linked protoporphyria", section on 'Afamelanotide'.)

Eosinophilia during prolonged antibiotic therapy (June 2015)

Eosinophilia is not uncommon in patients receiving prolonged intravenous (IV) antibiotics, but the prevalence and significance has not been extensively studied. In a prospective cohort study of 824 patients receiving prolonged intravenous antibiotic therapy, eosinophilia developed in 25 percent, appearing at a median of 15 days of therapy and peaking at a median absolute count of 726/mL (500 to 8610/mL) [26]. Although most patients with eosinophilia completed their courses without complications, one-third developed a hypersensitivity reaction involving rash or hepatic or renal involvement. Medication-associated eosinophilia does not mandate discontinuation of therapy but warrants close monitoring for evidence of hypersensitivity and consideration of alternative medications that could be substituted without compromising care. (See "Approach to the patient with unexplained eosinophilia", section on 'Medications and over the counter remedies'.)

Sunscreen use among adults in the United States (June 2015)

Although regular sunscreen use is a key message of sun-safety campaigns worldwide, data on the pattern of sunscreen use in the general population are limited. In the United States, a survey of over 4000 adults found that approximately 14 percent of men and 30 percent of women regularly used sunscreen on the face and other exposed skin when outside in the sun for more than one hour [27]. Regular use of sunscreen was associated with having sun-sensitive skin, higher annual household income, performing aerobic activity, and having children younger than 18. However, the use of sun protection measures other than sunscreen (eg, wearing hat or protective clothing) was not investigated. The results of this study indicate a need for sun-safety interventions targeting men, individuals with a lower perceived susceptibility to sun damage, and those for whom cost may be a barrier to sunscreen use. (See "Selection of sunscreen and sun-protective measures", section on 'Patterns of use'.)

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REFERENCES

Topic 87552 Version 4761.0

Wednesday, September 23, 2015

IMMUNOGLOBULIN E MEDIATED FOOD ALLERGY

Cincinnati Children's Hospital Medical Center Location S

PHOTOS:

Publish Date:	09/22/15
Media Contact:	Nick Miller, 513-803-6035

Cell Type May Help Explain Why Some People Have Dangerous Food Allergies

CINCINNATI--Researchers have discovered a new cell type that appears to drive life-threatening food allergies and may help explain why some people get severe allergic reactions and others do not.

Reporting their study data Sept. 22, 2015, in the journal Immunity, scientists at Cincinnati Children's Hospital Medical Center say their findings in mice should also provide insights into new therapeutic strategies and diagnostics for food allergies and anaphylactic shock triggered by the immune antibody IgE (immunoglobulin E).

The authors report discovery of what they call "IL-9-producing mucosal mast cells" or (MMC9 cells). The cells produce large amounts of an inflammatory immune protein called interlukin 9 (IL-9), which amplifies anaphylactic shock in response to ingested food. Prior to this study, the primary cellular source of IL-9 was unknown, according to the authors.

"Our study suggests that although you need to have some level of IgE to trigger a food allergy response, you also have to produce MMC9 cells to get a severe response and anaphylaxis," says Yui-Hsi Wang, PhD, lead investigator, a researcher in the Division of Allergy and Immunology at Cincinnati Children's and an assistant professor of pediatrics at the University of Cincinnati College of Medicine. "Without these cells you will not get severe food allergies."

Set off by certain foods like peanuts, shell fish and a host of others, IgE-associated food sensitivity prompts the immune systems of some children to surge out of control. Unless there is immediate medical intervention, this can trigger a molecular chain reaction in the intestines and other organs – leading to diarrhea, hypothermia, respiratory distress and shock.

About 40 percent of children have some IgE-associated food sensitivity, but only 8 percent of the 40 percent develop the severe food reactions that can lead to anaphylactic shock, according to Wang.

"Unfortunately the best medical intervention for these allergies remains avoiding the foods that cause them," he said. "We don't know why some patients develop such a strong response and why some don't. This is where we as basic scientists are coming in to see if we can use mouse models to learn this, because mice are very much like humans."

Wang and his colleagues suspect that some people are wired genetically to have higher or lower susceptibility to severe IgE-related allergic reactions. Still, it also remains unknown exactly how genetics contributes to these molecular chain reactions.

Just as people with food allergies have different degrees of susceptibility, so do mice. To account for this, the researchers conducted their study in several distinct strains of genetically bred mice. They gave the mice an egg white protein called ovalbumin to trigger allergic reactions and study biological reactions in the animals.

They observed that after allergic sensitization, some mouse strains generated large populations of MMC9 cells while other strains did not. Mice that did not produce MMC9 cells exhibited only minor allergic responses. Mice that produced intestinal MMC9 cells all had severe allergic reactions, regardless of whether they had low or high levels of IgE.

Wang and his colleagues report that production of MMC9 cells required the presence of type-2 CD4+ T helper immune cells and the proteins interlukin-4 and STAT6. By producing significant amounts of IL-9, the MMC9 cells caused mastocytosis and the production of mast cells, which may migrate out of the intestines to other organs as they secrete histamines and other molecules that cause anaphylaxis.

To verify that MMC9 cells were fueling severe allergic reactions in the mice, the researchers treated the mice with an antibody, which eliminated the cells and decreased food allergy symptoms. When MMC9 cells were transferred back into the same mice, the animals resumed exhibiting food allergy symptoms.

Researchers next conducted tests to see if their identification of MMC9 cells was relevant to the development of human food allergies. Analyzing small intestine biopsy samples from food allergy patients (who gave authorized consent) the scientists looked for molecular signatures of MMC9 cells. They found significantly increased expression of the Il9 genetic transcript and other related transcripts in the samples of food allergy patients, suggesting a possible connection.

Wang said the researchers are now trying to find the human equivalent (orthologue) of the MMC9 cells they found in their mouse models. One goal the researchers have is to identify that cell and its biological mediators to see if it possible to develop a biomarker that might allow development of a blood test for food allergies. Eventually, Wang said, the team wants to develop a blood test that would allow clinicians to determine which patients are at higher risk for severe food allergies, and to find improved treatments for food allergy.

Also working with Wang on the study were co-first authors and Cincinnati Children's colleagues Chun-Yu Chen, PhD and Jee-Boong Lee, PhD the Division of Allergy and Immunology.

Funding support for the study came from, the National Institutes of Health (AI090129-1, A1073553), the Digestive Health Center Pilot and Feasibility Award (P30 DK078392), the Campaign Urging Research for Eosinophilic Diseases (CURED) Foundation, the Buckeye Foundation and the Food Allergy Research Education Fund.

According to these findings and others, that is why I encourage the Medical Practice to perform an Immunoglobulin E, Test in Blood, before any other Allergy Testing.

for comments: Carlos E Mijares, MD, www.carlosmixares@gmail.com

www.centromedicodecaracas.com.ve

UC Researcher Primed to Study the Culprit Behind Dangerous Pean

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Monday, November 23, 2015

WHEAT GENOME PUZZLE / SECOND STAPLE IN FOOD ALLERGY, WORLDWIDE

On Biology