scholarly journals Metabolomics Distinguishes DOCK8 Deficiency from Atopic Dermatitis: Towards a Biomarker Discovery

Metabolites ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 274 ◽  
Author(s):  
Minnie Jacob ◽  
Xinyun Gu ◽  
Xian Luo ◽  
Hamoud Al-Mousa ◽  
Rand Arnaout ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Biomarker Discovery ◽  
Isotope Labeling ◽  
Immunoglobulin E ◽  
Clinical Symptoms ◽  
Elevated Serum ◽  
Severe Atopic Dermatitis ◽  
Serum Ige ◽  
Tryptophan Degradation ◽  
Dock8 Deficiency

Bi-allelic mutations in the dedicator of cytokinesis 8 (DOCK8) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient (n = 10) and AD (n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls (n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenylalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.

scholarly journals Topical Application of Herbal Mixture Extract Inhibits Ovalbumin- or 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Soon Re Kim ◽  
Han-Seok Choi ◽  
Hye Sook Seo ◽  
Youn Kyung Choi ◽  
Yong Cheol Shin ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Topical Application ◽  
Immunoglobulin E ◽  
Elevated Serum ◽  
Ethanol Extract ◽  
Inflammatory Cells ◽  
Skin Lesions ◽  
Serum Ige ◽  
Beneficial Effects ◽  
Blood Eosinophils

KM110329 is four traditional herbal medicine mixtures with anti-inflammatory properties. Atopic dermatitis (AD) is an inflammatory skin disease associated with enhanced T-helper2 (Th2) lymphocyte response to allergens that results in elevated serum eosinophil and Immunoglobulin E (IgE) levels and leukocyte infiltration in atopic skin sites. In this study, we investigated the effect of topical application of KM110329 ethanol extract on the ovalbumin (OVA) or 2,4-dinitrochlorobenzene- (DNCB-) induced AD mouse models. For that purpose, we observed the effects of KM110329 on blood eosinophils, skin mast cells, production of serum IgE, and expression of cytokine mRNA in the atopic dermatitis skin lesions of OVA allergen- or DNCB-treated BALB/c mice. KM110329 significantly reduced blood eosinophils cell numbers in OVA or DNCB-treated BALB/c mice. Histological analyses demonstrated decreased mast cell count as well as dermal infiltration by inflammatory cells. In the skin lesions, mRNA expression of interleukine (IL)-4, IL-13, and IL-17 was inhibited by KM110329. KM110329 also suppressed the production of serum IgE level in both the OVA- and DNCB-induced atopic dermatitis model. Taken together, our results showed that topical application of KM110329 extracts exerts beneficial effects in AD symptoms, suggesting that KM110329 might be a useful candidate for the treatment of AD.

scholarly journals Topical Application ofChrysanthemum indicum L.Attenuates the Development of Atopic Dermatitis-Like Skin Lesions by Suppressing Serum IgE Levels, IFN-γ, and IL-4 in Nc/Nga Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Sunmin Park ◽  
Jung Bok Lee ◽  
Suna Kang
Keyword(s):  
Atopic Dermatitis ◽  
Topical Application ◽  
Immunoglobulin E ◽  
Clinical Symptoms ◽  
Secondary Infection ◽  
Skin Lesions ◽  
Mrna Levels ◽  
Dorsal Skin ◽  
Gene Expressions ◽  
Serum Ige

Chrysanthemum indicum L. (CIL) is widely used as an anti-inflammatory agent in Asia and our preliminary study revealed that CIL reduced interleukin (IL)-4 and IL-13 in 2,4-dinitrochlorobenzene (DNCB)-treated HaCaT cells, a human keratinocyte cell line. We investigated the atopic dermatitis (AD) effect of topically applied CIL in mice with AD-like symptoms. After topical application of 1,3-butylen glycol (control), CIL-Low (5%), CIL-High (30%), or 0.1% hydrocortisone (HC) on the AD-like skin lesions in DNCB-treated NC/Nga mice for 5 weeks, the ear thickness, mast cell infiltration, and serum immunoglobulin E (IgE), IgG1, IL-4 and interferon (IFN)-γwere measured. The gene expressions of IL-4, IL-13, and IFN-γin the dorsal skin were assayed. CIL treatment dosedependently reduced severity of clinical symptoms of dorsal skin, ear thickness, and the number of mast cells and eosinophils. CIL-High significantly decreased serum IgE, IgG1, IL-4, and IFN-γlevels and reduced mRNA levels of IFN-γ, IL-4, and IL-13 in dorsal skin lesion. The improvement by CIL-High was similar to HC, but without its adverse effects such as skin atrophy maceration, and secondary infection. In conclusion, CIL may be an effective alternative substance for the management of AD.

scholarly journals Immunoglobulin E–Selective Immunoadsorption Reduces Peripheral and Skin-Bound Immunoglobulin E and Modulates Cutaneous IL-13 Expression in Severe Atopic Dermatitis

2019 ◽  
Vol 139 (3) ◽  
pp. 720-723 ◽  
Author(s):  
Kristian Reich ◽  
Anna Hartjen ◽  
Jeremias Reich ◽  
Julie Schröder ◽  
Nadine Steingrube ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Severe Atopic Dermatitis

Correlation between Total Serum Immunoglobulin E (IgE) and Absolute Eosinophil Count (AEC) in Allergic Diseases In Children

2020 ◽  
Vol 7 (1) ◽  
pp. 5-9
Author(s):  
Dr. Mayank Surana ◽  
Dr. Vineeta Pande ◽  
Dr. Sharad Agarkhedkar ◽  
Dr. Ajit Teegala
Keyword(s):  
Atopic Dermatitis ◽  
Bronchial Asthma ◽  
Eosinophil Count ◽  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Total Ige ◽  
Serum Ige ◽  
Absolute Eosinophil Count ◽  
Serum Total Ige ◽  
Total Immunoglobulin

Allergy, is a clinical expression of soluble factors like IgE, histamine or eosinophils found in serum or plasma of such patients. The products that are responsible for allergy are called as Allergens. Allergens normally induce IgE production which leads to type 1 hypersensitivity response on subsequent exposure to the same allergen. The target organs are mostly nose, lung, skin and gastrointestinal tract. Atopy is also considered as a triad of Atopic dermatitis, allergic rhinitis and bronchial asthma. Raised serum IgE and AEC are proven indicators of allergic phenomenon. Various studies show relationship between serum Immunoglobulin E level and total eosinophil count in population suffering from allergic diseases. Serum total Immunoglobulin E, total eosinophil count and specific IgE are all helpful for the diagnosis and treatment of allergic diseases. Objectives: 1.To Evaluate Serum Total IgE level in Children with allergic diseases.2. To Evaluate Absolute Eosinophil Count (AEC) in children with allergic diseases.3. To Correlate Serum Total Immunoglobulin E Level and Absolute Eosinophil Count (AEC) with allergic diseases. Methodology: Cross sectional study with 100 children in the age group 2-12 years with nasopharyngeal allergies (like bronchial asthma and atopic rhinitis) and skin allergies (like atopic dermatitis, urticaria) ,eye allergies were enrolled and serum IgE levels and AEC levels was done. Results: In present study Absolute eosinophil count was raised in 58% of cases Serum IgE was raised in 54% of cases. In present study, of 58% cases with raised Absolute eosinophil count 81% (47 cases) showed raised serum IgE levels. Conclusion: Absolute eosinophil count and serum Total IgE has been considered as a significant marker of allergic state and can be used as a marker of allergic response in atopic individuals. Raised serum IgE and AEC are more in nasobronchial allergy as compare to other systemic allergies. The elevated level of serum Total IgE and Absolute Eosinophil Count both shows Significant Correlation thus can be considered as a dependable laboratory investigation in diagnosing and categorizing allergic diseases.

scholarly journals Flow cytometry biomarkers distinguish DOCK8 deficiency from severe atopic dermatitis

2014 ◽  
Vol 150 (2) ◽  
pp. 220-224 ◽  
Author(s):  
Erin Janssen ◽  
Erdyni Tsitsikov ◽  
Waleed Al-Herz ◽  
Gerard Lefranc ◽  
Andre Megarbane ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Atopic Dermatitis ◽  
Severe Atopic Dermatitis ◽  
Dock8 Deficiency

scholarly journals The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutation

2020 ◽  
Author(s):  
Li Lin ◽  
Ying Wang ◽  
Bijun Sun ◽  
Luyao Liu ◽  
Wenjing Ying ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Immunoglobulin E ◽  
Clinical Symptoms ◽  
Elevated Serum ◽  
Chinese Patients ◽  
Onset Age ◽  
Loss Of Function ◽  
Peripheral Blood Mononuclear ◽  
Whole Exome ◽  
Genetic Features

Abstract Background: Loss-of-function (LOF) mutation in signal transducer and activator of transcription 3 (STAT3) was one of the causes of the hyper immunoglobulin E (IgE) syndrome (HIES), while gain-of-function mutation (GOF) in STAT3 leads to immune dysregulation diseases. We retrospectively report 11 LOF STAT3 patients and 1 GOF STAT3 patient and illustrate their onset age, common clinical symptoms, immunologic and molecular manifestation. Methods: 12 patients were enrolled in our study. Serum immunoglobulins, lymphocyte subset detection and whole-exome sequencing were performed. Results: The median onset age of STAT3-deficient patients was 1.89 years. Eczema, recurrent respiratory infection, apparent fever, abscesses and Staphylococcus aureus infection was the classical manifestation. Elevated serum IgE level is not entirely unanimous with high eosinophils counts. Moderate viral DNA was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common spot, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients obtained a notable improvement after received intravenous immunoglobulin (IVIG). Conclusion: We believe IVIG may help reduce the opportunity of infection in STAT3-deficient patients. Significant variance at onset age probably is a great challenge for clinicians and urgently needs early diagnosis and treatment.

scholarly journals Participation of Neuropeptides and β-endorphin in Pathogenesis of Atopic Dermatitis. Evaluation of Levocetirizine Effectiveness upon Neuropeptides' Levels at Children with Atopic Dermatitis

2009 ◽  
Vol 7 (2) ◽  
pp. 74-80
Author(s):  
V A Revyakina ◽  
A S Agaphonov ◽  
T B Sentsova ◽  
M P Phabrika
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Symptoms ◽  
Signs And Symptoms ◽  
Severe Atopic Dermatitis ◽  
Neurokinin A ◽  
Double Blind ◽  
Developmental Mechanisms ◽  
Days Of Therapy

Objective. Determination of the role of neuropeptides and p-endorphin in developmental mechanisms of atopic dermatitis, and assessment of the effectiveness of levocetirizine, a modern Hl-antihistamine, on atopic dermatitis symptoms and its influence on the SCORAD index in children with atopic dermatitis. Materials and methods. 84 children with atopic dermatitis of moderate-to-severe or severe clinical nature, aged 1 to 17 years, were enrolled in this (double-blind or open, randomised, etc.) study. Patients were treated with levocetirizine 5 mg once daily during 14 days. The levels of P substance, neurokinin A, neurokinin B, and p-endorphin in blood serum, as well as levocetirizine effectiveness on disease symptoms and the SCORAD index were evaluated. Results. Lower neuropeptide levels were associated with disease severity; children with severe atopic dermatitis had lower neuropeptide values. Before treatment, SCORAD index in children with severe atopic dermatitis was 76,5±11,3, and after 7 days of therapy SCORAD index was 14±6,2 points (p< 0,01). By the 7th day after treatment initiation, the acute atopic dermatitis became of subacute nature and was accompanied by a regression of the cutaneous eruption in the form of significant decreasing of skin manifestations and pruritus, absence of new eruption and normalized sleep. In children with moderate-to-severe atopic dermatitis the SCORAD index before levocetirizine treatment was 44,2±3,4 points; on the 3rd day, this index was 20,4±2,6 points; and on the 7th day there was a complete absence of clinical symptoms of the main disease. Levocetirizine administration led to the disappearance of the disease clinical symptoms and pruritus in children with moderate-to-severe atopic dermatitis. Conclusion. This trial demonstrated that neuropeptides are involved in the developmental mechanisms of atopic dermatitis and that levocetirizine can significantly improve the signs and symptoms of children with moderate-to-severe or severe atopic dermatitis.

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