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1.
Nat Commun ; 13(1): 5669, 2022 09 27.
Article in English | MEDLINE | ID: mdl-36167830

ABSTRACT

IgE is central to the development of allergic diseases, and its neutralization alleviates allergic symptoms. However, most of these antibodies are based on IgG1, which is associated with an increased risk of fragment crystallizable-mediated side effects. Moreover, omalizumab, an anti-IgE antibody approved for therapeutic use, has limited benefits for patients with high IgE levels. Here, we assess a fusion protein with extracellular domain of high affinity IgE receptor, FcεRIα, linked to a IgD/IgG4 hybrid Fc domain we term IgETRAP, to reduce the risk of IgG1 Fc-mediated side effects. IgETRAP shows enhanced IgE binding affinity compared to omalizumab. We also see an enhanced therapeutic effect of IgETRAP in food allergy models when combined with Bifidobacterium longum, which results in mast cell number and free IgE levels. The combination of IgETRAP and B. longum may therefore represent a potent treatment for allergic patients with high IgE levels.


Subject(s)
Bifidobacterium longum , Food Hypersensitivity , Bifidobacterium longum/metabolism , Dietary Supplements , Food Hypersensitivity/therapy , Humans , Immunoglobulin D , Immunoglobulin E , Immunoglobulin G , Omalizumab/therapeutic use , Receptors, IgE/metabolism
2.
Childs Nerv Syst ; 27(1): 63-70, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20680301

ABSTRACT

OBJECTS: Tuberous sclerosis complex (TSC) is a dysgenetic syndrome involved in multiple organs, and the pathognomonic cortical tuber act as an epileptic substrate. The amino acid transport system L (LAT) is a major nutrient transport system, and LAT1 is highly expressed in malignant tumors to support tumor cell growth. To study the life-long epilepsy from the cortical tuber, the expression of LAT1 in balloon cells and dysplastic neurons of the cortical tuber is investigated. MATERIALS AND METHODS: LAT1 expression was investigated by LAT1 mRNA using reverse transcription-polymerase chain reaction and immunohistochemical staining with anti-human LAT1 antibody in nine patients with TSC and three control brains. CONCLUSION: LAT1 mRNA was detectable only in fresh-frozen tissues of TSC, and it was upregulated in the cortical tuber lesion. While the LAT1 immunopositivity of control brains was limited in the capillary endothelial cells in the gray matter, increased LAT1 immunopositivity was noted in balloon cells of the cortical tubers in addition to the capillary endothelial cells as shown in control brains. Linear and strong immunopositivity along the cell membrane and cytoplasm of the balloon cells, and weakly granular immunopositivity in their cytoplasm were noted. Increased expression of LAT1 in the balloon cells is important for the active transport of large neutral amino acids into the balloon cells, and that the biologic process may play an important role in the active protein synthesis with metabolic maintenance of balloon cells in cortical tubers of patients with TSC.


Subject(s)
Large Neutral Amino Acid-Transporter 1/biosynthesis , Neurons/metabolism , Tuberous Sclerosis/metabolism , Adult , Child, Preschool , Female , Humans , Immunohistochemistry , Large Neutral Amino Acid-Transporter 1/genetics , Male , Middle Aged , Neurons/pathology , RNA, Messenger/analysis , Reverse Transcriptase Polymerase Chain Reaction , Tuberous Sclerosis/pathology , Up-Regulation , Young Adult
4.
Int Arch Allergy Immunol ; 150(2): 156-63, 2009.
Article in English | MEDLINE | ID: mdl-19439981

ABSTRACT

BACKGROUND: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. METHODS: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. RESULTS: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497-13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236-22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540-13.449). This p value remained significant after correction for multiple comparison. CONCLUSION: The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated.


Subject(s)
Asthma/chemically induced , Asthma/genetics , HLA-DP Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Haplotypes/genetics , Membrane Glycoproteins/genetics , Occupational Diseases/genetics , Toluene 2,4-Diisocyanate/adverse effects , Adult , Asthma/physiopathology , Female , Forced Expiratory Volume/physiology , Gene Frequency/genetics , HLA-DP beta-Chains , HLA-DQ beta-Chains , HLA-DRB1 Chains , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Korea , Male , Middle Aged , Occupational Diseases/chemically induced , Occupational Diseases/immunology , Risk Factors , Toluene 2,4-Diisocyanate/immunology
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