Normal pregnancy and allergy are both characterized by a T helper (Th) 2 deviation. In the current study, we hypothesized that paternal antigen-induced cytokine responses during pregnancy would be deviated toward Th2 and an anti-inflammatory profile, and that the Th2 deviation would be more pronounced in allergic pregnant women. Blood samples were collected longitudinally on three occasions during pregnancy and two occasions post partum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Twelve women fulfilled the criteria for allergy (allergic symptoms and circulating immunoglobulin [Ig] E antibodies to inhalant allergens) and 20 were non-allergic (nonsensitized without symptoms). The levels of Th1- and Th2-associated cytokines and chemokines, the Th17 cytokine IL-17 and the anti-inflammatory cytokine IL-10 of the groups were compared. Paternal antigen-induced IL-4 and IL-10 responses increased between the first and the third trimester. Allergy was associated with decreased paternal antigen-induced IFN-γ and CXCL10 secretion in the nonpregnant state (one year pp) and also decreased IFN-γ/IL-4 and IFN-γ/IL-13 ratios during pregnancy. We also observed a decreased paternal antigen-induced IL-10 response in allergic compared with non-allergic women during pregnancy, along with a decreased IL-10/IL-13 ratio. In conclusion, our findings support the hypothesis of lower Th1 responses toward paternal antigens in allergic than in non-allergic women, but also indicate that allergy is associated with a lower capacity to induce anti-inflammatory IL-10 responses after paternal antigen stimulation during pregnancy. / <p>Funding Agencies|Swedish Research Council||Cancer and Allergy Association||Olle Engkvist Foundation||Vardal Foundation for Health Care Sciences and Allergy Research||National Swedish Association against Allergic Diseases||Linkoping University Hospital||</p>

In this study, Sezawa-mode surface acoustic wave (SAW) devices were employed to construct the allergy biosensor. To fabricate Sezawa-mode SAW devices, the RF magnetron sputtering method for the growth of piezoelectric ZnO thin films onto Si3N4/Si is adopted and influences of the sputtering parameters are investigated. The properties of the ZnO thin films are investigated by X-ray diffraction and scanning electron microscopy which reveal a high c-axis-preferred orientation. A back-etched resonator is used in this study. The wet etching of (100)-oriented silicon wafers is used to form a back-side cavity which is used as the sensing area. Low-stress silicon nitride was deposited by low-pressure chemical vapor deposition (LPCVD) as the etching mask for the integrated SAW device. To investigate the sensing characteristics of SAW, gold (Au) layer was initially deposited onto the sensing area of SAW devices as the binding layer in biochemical sensor and the surface of the Au layer was treated with oxygen plasma to enhance the hydrophilic properties of the Au layer. The self assembly monolayers (SAMs) is used to decorate surface of Au layer and the sandwiched enzyme-linked immunosorbent assay is used for detecting the concentration variation of immunoglobulin E (IgE) in human serum. The frequency response is measured using an E5071C network analyzer. The resonance frequency of the Sezawa-mode SAW device is 1.49 GHz. The sensitivities of the Sezawa-mode biosensor is calculated to be 6.64 MHz cm2/ng for human IgE detection.

published_or_final_version / Pathology / Master / Master of Medical Sciences

<p>The prevalence of allergic disease such as peanut (PN) allergy has increased within the last century. Environmental factors have been associated with an increased risk of developing allergic diseases. The severity of allergic diseases has also increased and clinical trials are investigating allergen-specific immunotherapy as a method to treat allergies. The purpose of this work was to identify a vaccine adjuvant that induced potent antigen-specific Th1 immune responses and determine its ability to reduce the development and severity of Th2- mediated allergic disease, using models of peanut hypersensitivity.</p><p>Three studies were performed. The first study compared a variety of vaccine adjuvants to identify a potent adjuvant with strong Th1-associated activity. This study verified that the Toll-like receptor (TLR) ligand CpG could induce potent Th1-associated immune responses. The second study tested the ability of environmental endotoxin levels and alum-adjuvanted vaccines to modulate the development of allergic disease using a mouse model of peanut allergy. Additionally, the TLR ligands, CpG and MPL, were combined with alum-adjuvanted vaccines to determine their ability to further impact allergic disease development. Results suggested that the addition of CpG to an alum-adjuvanted vaccine indirectly modified host immunity in a manner that decreased the development of PN-induced allergic disease. The last study evaluated the ability of CpG to reduce the severity of peanut allergy symptoms when combined with peanut in an immunotherapy formulation administered to peanut-hypersensitive mice. Nasal immunotherapy with PN + CpG but not PN alone or CpG alone reduced the severity of PN-induced anaphylaxis in hypersensitive mice. PN-hypersensitive mice treated with PN + CpG displayed an increased PN-specific IgG2c and IFN-γ responses. A reduction in allergic disease severity in PN-hypersensitive mice correlated with an increase in PN-specific IgG2c, IFN-γ and IL-10 responses and a reduction in PN-specific IL-13 responses, suggesting a shift from Th2 responses towards Th1 and/or T regulatory cell responses.</p><p>Taken together, the data obtained from these studies demonstrate the potent activity of CpG to induce antigen-specific Th1-associated immune responses and also reduce the severity of peanut-hypersensitivity in mice through direct and indirect association with peanut allergens.</p> / Dissertation

T helper type--2 (Th2) immunity orchestrates responses against extracellular pathogens under normal conditions and mediates pathogenic responses against innocuous substances when dysregulated, leading to allergic disease. Among the cytokines expressed by Th2 cells, interleukin (IL)--13 has emerged as a critical effector molecule in Th2 responses and common IL13 variants are associated with allergy--related phenotypes in populations of distinct ethnic background. IL13 expression in human T cells is paralleled by extensive IL13 locus remodeling, which results in the appearance of multiple DNase I hypersensitive (HS) sites. Among these, HS4 in the distal IL13 promoter is constitutively present in both naive and polarized Th2 cells, and spans a single nucleotide polymorphism, IL13--1512AC (rs1881457), which is common and strongly associated with total serum IgE levels. This dissertation combines in vitro and ex vivo approaches to characterize the role of HS4 in the regulation of IL13 gene expression and to provide novel insights into the mechanisms that underlie the association between IL13--1512AC and allergic disease.The results showed that HS4 acts as a novel cis--acting element that up--regulates IL13 transcription in activated Th2 cells. The enhancing activity of HS4 mapped within the 3' end of this element and was dependent on binding/recruitment of the transcription factors NF90 and NF45. Moreover, the IL13--1512C risk allele significantly enhanced HS4--dependent IL13 expression by creating a binding site for the transcription factor Oct--1. The increased expression of the --1512C allele was dependent on endogenous levels of Oct--1. Collectively, these results illustrate how a functional variant in an important regulatory element may modulate susceptibility to a common complex disease.

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