An allergy can refer to several kinds of immune reactions including Type I hypersensitivity in which a person's body is hypersensitised and develops IgE type antibodies to typical proteins. When a person is hypersensitised, these substances are known as allergens. The word allergy derives from the Greek words allos meaning "other" and ergon meaning "work". Type I hypersensitivity is characterised by excessive activation of mast cells and basophils by immunoglobulin E resulting in a systemic inflammatory response that can result in symptoms as benign as a runny nose, to life-threatening anaphylactic shock and death.

Allergy is a very common disorder and more than 50 million Americans suffer from allergic diseases. Allergies are the 6th leading cause of chronic disease in the United States, costing the health care system $18 billion annually (Allergy statistics).

History

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The term and concept of "allergy" was coined by a Viennese pediatrician named Clemens von Pirquet in 1906 ^*. He observed that the symptoms of some of his patients might have been a response to outside allergens such as dust, pollen, or certain foods. For a long time all hypersensitivities were thought to stem from the improper action of inflammatory immunoglobulin class IgE, however it soon became clear that several different mechanisms utilizing different effector molecules were responsible for the myriad of disorders previously classified as "allergies". A new four-class (now five) classification scheme was designed by P. G. H. Gell and R. R. A. Coombs. Allergy has since been kept as the name for Type I Hypersensitivity, characterised by classical IgE mediation of effects.

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Clinical and Molecular Allergy - Latest Articles

Clara cell protein in nasal lavage fluid and nasal nitric oxide - biomarkers with anti-inflammatory properties in allergic rhinitis
Kristina IranderJorgen PalmMagnus BorresBijar Ghafouri Mon, 06 Feb 2012 00:00:00 -0000
Background: Clara cell protein (CC16) is ascribed a protective and anti-inflammatory role in airway inflammation. Lower levels have been observed in asthmatic subjects as well as in subjects with intermittent allergic rhinitis than in healthy controls. Nasal nitric oxide (nNO) is present in high concentrations in the upper airways, and considered a biomarker with beneficial effects, due to inhibition of bacteria and viruses along with stimulation of ciliary motility. The aim of this study was to evaluate the presumed anti-inflammatory effects of nasal CC16 and nNO in subjects with allergic rhinitis. Methods: The levels of CC16 in nasal lavage fluids, achieved from subjects with persistent allergic rhinitis (n = 13), intermittent allergic rhinitis in an allergen free interval (n = 5) and healthy controls (n = 7), were analyzed by Western blot. The levels of nNO were measured by the subtraction method using NIOX(R). The occurrences of effector cells in allergic inflammation, i.e. metachromatic cells (MC, mast cells and basophiles) and eosinophils (Eos) were analyzed by light microscopy in samples achieved by nasal brushing. Results: The levels of CC16 correlated with nNO levels (r2 = 0.37; p = 0.02) in allergic subjects.The levels of both biomarkers showed inverse relationships with MC occurrence, as higher levels of CC16 (p = 0.03) and nNO (p = 0.05) were found in allergic subjects with no demonstrable MC compared to the levels in subjects with demonstrable MC. Similar relationships, but not reaching significance, were observed between the CC16 and nNO levels and Eos occurrence. The levels of CC16 and nNO did not differ between the allergic and the control groups. Conclusions: The correlation between nasal CC16 and nNO levels in patients with allergic rhinitis, along with an inverse relationship between their levels and the occurrences of MC in allergic inflammation, may indicate that both biomarkers have anti-inflammatory effects by suppression of cell recruitment. The mechanisms behind these observations warrant further analyses.
Enhanced effects of cigarette smoke extract on inflammatory cytokine expression in IL-1beta-activated human mast cells were inhibited by Baicalein via regulation of the NF-kappaB pathway
David ChiTa-Chang LinKenton HallTuanzhu HaChuanfu LiZong Doa WuThomas SoikeGuha Krishnaswamy Mon, 06 Feb 2012 00:00:00 -0000
Background: Human mast cells are capable of a wide variety of inflammatory responses and play a vital role in the pathogenesis of inflammatory diseases such as allergy, asthma, and atherosclerosis. We have reported that cigarette smoke extract (CSE) significantly increased IL-6 and IL-8 production in IL-1-activated human mast cell line (HMC-1). Baicalein (BAI) has anti-inflammatory properties and inhibits IL-1- and TNF--induced inflammatory cytokine production from HMC-1. The goal of the present study was to examine the effect of BAI on IL-6 and IL-8 production from CSE-treated and IL-1-activated HMC-1. Methods: Main-stream (Ms) and Side-stream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI-1640 medium. Two ml of HMC-1 at 1 x 106 cells / mL were cultured with CSE in the presence or absence of IL-1 (10 ng / mL) for 24 hrs. A group of HMC-1 cells stimulated with both IL-1beta (10 ng/ml) and CSE was also treated with BAI. The expression of IL-6 and IL-8 was assessed by ELISA and RT-PCR. NF-kappaB activation was measured by electrophoretic mobility shift assay (EMSA) and IkappaBalpha degradation by Western blot. Results: Both Ms and Ss CSE significantly increased IL-6 and IL-8 production (p < 0.001) in IL-1-activated HMC-1. CSE increased NF-kappaB activation and decreased cytoplasmic IkappaBalpha proteins in IL-1beta-activated HMC-1. BAI (1.8 to 30 muM) significantly inhibited production of IL-6 and IL-8 in a dose-dependent manner in IL-1beta-activated HMC-1 with the optimal inhibition concentration at 30 muM, which also significantly inhibited the enhancing effect of CSE on IL-6 and IL-8 production in IL-1beta-activated HMC-1. BAI inhibited NF-kappaB activation and increased cytoplasmic IkappaBalpha proteins in CSE-treated and IL-1beta-activated HMC-1. Conclusions: Our results showed that CSE significantly increased inflammatory cytokines IL-6 and IL-8 production in IL-1-activated HMC-1. It may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. BAI inhibited the production of inflammatory cytokines through inhibition of NF-kappaB activation and IkappaBalpha phosphorylation and degradation. This inhibitory effect of BAI on the expression of inflammatory cytokines induced by CSE suggests its usefulness in the development of novel anti-inflammatory therapies.
Defining the molecular role of gp91phox in the immune manifestation of acute allergic asthma using a preclinical murine model.
Ena Ray BanerjeeWilliam Henderson Wed, 04 Jan 2012 00:00:00 -0000
ObjectiveThe phenomena manifested during inflammation require interplay between circulating effector cells, local resident cells, soluble mediators and genetic host factors to establish, develop and maintain itself. Of the molecues involed in the initiation and perpetuation of acute allergic inflammation in asthma, the involvement of effector cells in redox reactions for producing O2- (superoxide anion) through the mediation of NADPH oxidase is a critical step. Prior data suggest that reactive oxygen species (ROS) produced by NADPH oxidase homologues in non-phagocytic cells play an important role in the regulation of signal transduction, while macrophages use a membrane-associated NADPH oxidase to generate an array of oxidizing intermediates which inactivate MMPs on or near them.Materials and Methods and TreatmentTo clarify the role of gp91phox subunit of NADPH oxidase in the development and progression of an acute allergic asthma phenotype, we induced allergen dependent inflammation in a gp91phox-/- single knockout and a gp91phox-/-MMP-12-/- double knockout mouse models. Results: In the knockout mice, both inflammation and airway hyperreactivity were more extensive than in wildtype mice post-OVA. Although OVA-specific IgE in plasma were comparable in wildtype and knockout mice, enhanced inflammatory cell recruitment from circulation and cytokine release in lung and BALf, accompanied by higher airway resistance as well as Penh in response to methacholine, indicate a regulatory role for NADPH oxidase in development of allergic asthma. While T cell mediated functions like Th2 cytokine secretion, and proliferation to OVA were upregulated synchronous with the overall robustness of the asthma phenotype, macrophage upregulation in functions such as proliferation, and mixed lymphocyte reaction indicate a regulatory role for gp91phox and an overall non-involvement or synergistic involvement of MMP12 in the response pathway (comparing data from gp91phox-/- and gp91phox-/-MMP-12-/- mice).
The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children
Komei ItoMasaki FutamuraRobert MoverareAkira TanakaTsutomu KawabeTatsuo SakamotoMagnus Borres Mon, 02 Jan 2012 00:00:00 -0000
Background: Cow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, alpha-lactalbumin and beta-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness. Methods: Eighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n=61) or non-CMA (n=22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized). Results: The CMA group had significantly higher levels of milk-, casein- and beta-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kUA/L corresponding to 100% specificity. All but one of the CMA children aged >5 years had casein-sIgE levels >6.6 kUA/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children. Conclusions: High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.
Case report of a young child with Disseminated Histoplasmosis and review of Hyper Immunoglobulin E Syndrome (HIES)
Wilson RobinsonSandra ArnoldChristie MichaelJohn VickeryRobert SchoumacherEniko PivnickJewell WardVijaya NagabhushanamDukhee Lew Tue, 29 Nov 2011 00:00:00 -0000
Type 1 hyper IgE syndrome (HIES), also known as Job's Syndrome, is an autosomal dominant disorder due to defects in STAT3 signaling and Th17 differentiation. Symptoms may present during infancy but diagnosis is often made in childhood or later. HIES is characterized by immunologic and non-immunologic findings such as recurrent sinopulmonary infections, recurrent skin infections, multiple fractures, atopic dermatitis and characteristic facies. These manifestations are accompanied by elevated IgE levels and reduced IL-17 producing CD3+CD4+ T cells. Diagnosis in young children can be challenging as symptoms accumulate over time along with confounding clinical dilemmas. A NIH clinical HIES scoring system was developed in 1999, and a more recent scoring system with fewer but more pathogonomonic clinical findings was reported in 2010. These scoring systems can be used as tools to help in grading the likelihood of HIES diagnosis. We report a young child ultimately presenting with disseminated histoplasmosis and a novel STAT3 variant in the SH2 domain.
Chronic Granulomatous Disease, the McLeod Phenotype and the Contiguous Gene Deletion Syndrome - A Review
Casey WatkinsJohn LitchfieldEunkyung SongGayatri JaishankarNiva MisraNikhil HollaMichelle DuffourcGuha Krishnaswamy Wed, 23 Nov 2011 00:00:00 -0000
Chronic Granulomatous Disease (CGD), a disorder of the NADPH oxidase system, results in phagocyte functional defects and subsequent infections with bacterial and fungal pathogens (such as Aspergillus species and Candida albicans). Deletions and missense, frameshift, or nonsense mutations in the gp91phox gene (also termed CYBB), located in the Xp21.1 region of the X chromosome, are associated with the most common form of CGD. When larger X-chromosomal deletions occur, including the XK gene deletion, a so-called "Contiguous Gene Deletion Syndrome" may result. The contiguous gene deletion syndrome is known to associate the Kell phenotype/McLeod syndrome with diseases such as X-linked chronic granulomatous disease, Duchenne muscular dystrophy, and X-linked retinitis pigmentosa. These patients are often complicated and management requires special attention to the various facets of the syndrome.
Early Gene Expression Changes with Rush Immunotherapy
Laurie DavisSumit BhutaniSherry BarnettDavid Khan Fri, 30 Sep 2011 00:00:00 -0000
Background: To examine whether whole genome expression profiling could reveal changes in mRNA expression of peripheral blood mononuclear cells (PBMC) from allergic patients undergoing rush immunotherapy (RIT) that might be manifest within the first few months of treatment. Methods: For this study, PBMC from three allergic patients undergoing RIT were assessed at four timepoints: prior to RIT, at 1 week and 7 week post-RIT, during build-up and at 4 months, after establishment of a maintenance dose. PBMC mRNA gene expression changes over time were determined by oligonucleotide microarrays using the Illumina Human-6 BeadCh Subscribe to Allergies RSS feed