Association between asthma, rhinitis and conjunctivitis multimorbidities with molecular IgE sensitization in adults

https://ift.tt/2DJgZlI

Multiple skin lesions on a background of hypergammaglobulinaemia

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Chylothorax after hepatectomy: a case report

Chylothorax is the accumulation of chyle within the pleural space. Chylothorax can occur as a complication after multiple different types of surgery, most frequently after thoracic surgery, albeit with an inci...

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Future research priorities for lichen sclerosus – results of a James Lind Alliance Priority Setting Partnership

Abstract

Lichen sclerosus (LS) is a chronic, inflammatory genital skin condition affecting men, women and children. Long‐term complications include loss of normal anatomy from scarring, and malignant transformation. Uncertainties exist about the cause, diagnosis and management of LS. For example, the aetiology is contested; evidence suggests that chronic irritation by occluded urine is important in males,¹ however, autoimmune mechanisms are proposed in females.² Genetic associations are suggested in both sexes. Existing evidence on which to make recommendations about management and the prevention of malignancy, is generally poor quality.

This article is protected by copyright. All rights reserved.

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Bortezomib-Induced Pulmonary Toxicity: A Case Report and Review of Literature

Bortezomib, a proteasome inhibitor, is an established therapy against multiple myeloma. Bortezomib-induced lung injury, although not appreciated during the introductory time of the medication, has now been highlighted in multiple case reports. The objective of this study is to report a case of bortezomib-induced lung injury, review current literature, and perform exploratory analysis.

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A Case Report of Acute Airway Compromise due to Subcutaneous Emphysema

In the acute management of a trauma patient, airway patency is of utmost importance. The present case describes a male patient who presented with delayed severe upper airway obstruction secondary to massive subcutaneous emphysema following blunt traumatic injury two days previously. Airway compromise is a rarely described but serious complication of subcutaneous emphysema. Current management of subcutaneous emphysema and its association with pneumothorax is summarized. Early decompression of underlying pneumothoraces in patients with significant subcutaneous emphysema should be performed to avoid this rare complication.

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A pilot study on the allergen-specific IgE to molecular components on polysensitized mite allergic asthmatic patients in Guangzhou, China

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Haisheng Hu, Wenting Luo, Zehong Wu, Chuanxu Cai, Huimin Huang, Baoqing Sun

Abstract

Objective

Using multiplex microarray-based component resolved diagnosis (CRD) to investigate the allergen sensitization profile of allergic asthma patients in southern China.

Method

Serum samples from 57 polysensitized mite allergic asthmatic patients in a tertiary referral centre of southern China were tested with multiplex CRD (ISAC) for specific immunoglobulin E (sIgE) against 112 single allergen and components. Result was then compared with those from singleplex ImmunoCAP.

Results

With ISAC, the highest sensitization was seen for nDer f 1 (71.9%), rDer f 2 (73.7%), nDer p 1 (70.2%) and rDer p 2 (66.7%), whereas rDer p 10 and other storage mites' components only showed 10% positivity. rFel d 1 and rCan f 1 were found positive in 29.8% and 14.0% samples respectively. Other epithelia components had less than 7.0% positive rate. Sensitization to pollen components was dominated by nCyn d 1 (17.5%) and nPhl p 4 (12.3%), Carbohydrate cross-reactive determinants (CCD) was positive in 4 patients who were also positive to nPhl p 4, nCyn d 1 and rPla a 2, and all of them have combined asthma and rhinitis. The sensitivity to mold (rAsp f 3), cockroach (nBla g 7) and Anisakis simplex component (rAni s 3) were all the same at 8.8%. 93.0% patients were sensitive to more than one component, with more than half of them (57.9%) positive to five or more components.

Patients with combined asthma and rhinitis (AA + AR) were sensitive to more components than those with asthma only (AA). Positive rate to nPhl p 4 was significantly higher in patients with AA + AR than with AA only (χ² = 4.31, P =  0.038).

Compared with ImmunoCAP, ISAC showed a similar high detection rate for D. pteronyssinus and D. farinae, but only 10.0% of B. tropicalis sensitive patients were positive to rBlo t 5. Optimal scale analysis on correlation of allergens components showed rDer p 10 was associated to food allergy.

Conclusion

Being the first multiplex microarray based CRD study on southern Chinese, ISAC showed house dust mites components were the major allergen components led to sensitization in asthmatic patients. Patients with combined AA + AR were sensitive to more components than those with AA only. Other components with higher positive rate include pollen components nCyn d 1, nPhl P 4 and animal dander components rFel d 1 and rCan f 1. For B. tropicalis, the rBlo t 5 in ISAC may not represent the major Blomia component in southern Chinese patients.

https://ift.tt/2BxV2ER

Immuno-informatics based approaches to design a novel multi epitope-based vaccine for immune response reinforcement against Leptospirosis

Publication date: December 2018

Source: Molecular Immunology, Volume 104

Author(s): Majid Validi, Ahmad Karkhah, Vijay Kumar Prajapati, Hamid Reza Nouri

Abstract

Leptospirosis is known as a zoonotic disease of global importance originated from infection with the spirochete bacterium Leptospira. Although several leptospirosis vaccines have been tested, the vaccination is relatively unsuccessful in clinical application despite decades of research. Therefore, this study was conducted to construct a novel multi-epitope based vaccine against leptospirosis by using Hap1, LigA, LAg42, SphH and HSP58 antigens. T cell and IFN gamma epitopes were predicted from these antigens. In addition, to induce strong CD4⁺ helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) and helper epitopes selected from Tetanus toxin fragment C (TTFrC) were applied. Moreover, for boosting immune response, Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was added to the construct as an adjuvant. Finally, selected epitopes were linked together using EAAAK, GPGPG, AAY and HEYGAEALERAG linkers. Based on the predicted epitopes, a multi-epitope vaccine was construct with 490 amino acids. Physico-chemical properties, secondary and tertiary structures, stability, intrinsic protein disorder, solubility, and allergenicity of this vaccine construct were assessed by applying immunoinformatics analyses. A soluble, and non-allergic protein with a molecular weight of 53.476 kDa was obtained. Further analyses validated the stability of the chimeric protein and the predicted epitopes in the chimeric vaccine indicated strong potential to induce B-cell and T-cell mediated immune response. Therefore, immunoinformatics analysis showed that the modeled multi-epitope vaccine can properly stimulate the both T and B cells immune responses and could potentially be used for prophylactic or therapeutic usages.

Graphical abstract

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Phosphatidylinositol 3-Kinase/Akt signal pathway resists the apoptosis and inflammation in human extravillous trophoblasts induced by Porphyromonas gingivalis

Publication date: December 2018

Source: Molecular Immunology, Volume 104

Author(s): Haiying Guo, Hongyu Ren, Shanshan Liang, Yaoting Ji, Han Jiang, Ping Zhang, Minquan Du

Abstract

Epidemiological studies suggested that periodontitis is a risk factor for pregnancy complications including preterm birth. Porphyromonas gingivalis, a vital periodontal pathogen found in amniotic fluid and intact membranes of women who deliver preterm low birth weight infants, is thought to contribute to preterm labor. However, molecular and cellular interactions between P. gingivalis and placental cells are not clear. In this study, we investigated the effect of P. gingivalis on human extravillous trophoblasts and observed that it triggered apoptosis and inflammation and that Akt was activated in this process. In addition, when Akt activation was inhibited, apoptosis and inflammation was significantly increased. Thus, P. gingivalis infection contributes to preterm low birth weight infants by triggering excessive inflammation and increasing apoptosis in trophoblasts and that the Phosphatidylinositol 3-Kinase/Akt signaling pathway is involved in the regulation of Pg-induced apoptosis and inflammation.

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HLA-G, -E and -F regulatory and coding region variability and haplotypes in the Beninese Toffin population sample

Publication date: December 2018

Source: Molecular Immunology, Volume 104

Author(s): Paulin Sonon, Ibrahim Sadissou, Léonidas Tokplonou, Kuumaaté K.G. M'po, Sonya S.C. Glitho, Privat Agniwo, Moudachirou Ibikounlé, Juliana Doblas Massaro, Achille Massougbodji, Philippe Moreau, Audrey Sabbagh, Celso T. Mendes-Junior, Kabirou A. Moutairou, Erick C. Castelli, David Courtin, Eduardo A. Donadi

Abstract

HLA-G/E/F genes exhibit immunomodulatory properties and are expressed in placenta. Little attention has been devoted to the study of these genes in sub-Saharan African populations, which are yet the most diverse. To fill this gap, we evaluated the complete gene variability, approximately 5.1 kb for HLA-G (n = 149), 7.7 kb for HLA-E (n = 150) and 6.2 kb for HLA-F (n = 152) in the remote Beninese Toffin population, using massive parallel sequencing. Overall, 96, 37 and 68 variable sites were detected along the entire HLA-G, -E and -F, respectively, arranged into region-specific haplotypes; i.e., promoter haplotypes (16, 19, and 15 respectively), coding haplotypes (19, 15, and 29 respectively), 3' untranslated region (3′UTR) haplotypes (12, 7 and 2, respectively) and extended haplotypes (33, 31 and 32 respectively). All promoter/coding/3'UTR haplotypes followed the patterns already described in worldwide populations. HLA-E was the most conserved, exhibiting mainly two full-length encoded-molecules (E*01:01 and E*01:03), followed by HLA-F, three full-length proteins (F*01:01, F*01:02 and F*01:03) and HLA-G, four proteins: three full-length (G*01:01, G*01:03 and G*01:04) and one truncated (G*01:05N). Although HLA-G/E/F alleles in the Toffin population were the most frequently observed worldwide, the frequencies of the coding haplotypes were closely similar to those described for other African populations (Guinea-Conakry and Burkina-Faso), when compared to non-African ones (Brazilian), indicating that variable sites along these genes were present in Africa before human dispersion.

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Editorial Board

Publication date: December 2018

Source: Molecular Immunology, Volume 104

Author(s):

https://ift.tt/2BvIYny

KIR2DL4-HLAG interaction at human NK cell-oligodendrocyte interfaces regulates IFN-γ-mediated effects

Publication date: Available online 24 November 2018

Source: Molecular Immunology

Author(s): P.P. Banerjee, L. Pang, S.S. Soldan, S.M. Miah, A. Eisenberg, S. Maru, A. Waldman, E.A. Smith, Y. Rosenberg-Hasson, D. Hirschberg, A. Smith, D.V. Ablashi, K.S. Campbell, J.S. Orange

Abstract

Interactions between germline-encoded natural killer (NK) cell receptors and their respective ligands on tumorigenic or virus-infected cells determine NK cell cytotoxic activity and/or cytokine secretion. NK cell cytokine responses can be augmented in and can potentially contribute to multiple sclerosis (MS), an inflammatory disease of the central nervous system focused upon the oligodendrocytes (OLs). To investigate mechanisms by which NK cells may contribute to MS pathogenesis, we developed an in vitro human model of OL-NK cell interaction. We found that activated, but not resting human NK cells form conjugates with, and mediate cytotoxicity against, human oligodendrocytes. NK cells, when in conjugate with OLs, rapidly synthesize and polarize IFN-γ toward the OLs. IFN-γ  is capable of reducing myelin oligodendrocyte and myelin associated glycoproteins (MOG and MAG) content. This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population. These data collectively suggest a mechanism by which NK cells can promote pathogenic effects upon OLs.

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Perinatal probiotic intervention prevented allergic disease in a Caesarean‐delivered subgroup at 13‐year follow‐up

Abstract

Background

The long‐term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial.

Objective

To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age.

Methods

Pregnant women (n=1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomised to receive a mixture of probiotics (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double‐blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13‐year follow‐up the participants were requested to return a questionnaire and to provide a blood sample.

Results

A questionnaire was returned by 642 participants (63.1% of intention‐to‐treat infants) and 459 provided a blood sample. In the whole cohort there were no statistically significant differences in doctor‐diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant‐specific IgE‐sensitisation (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (p=0.040). In a post hoc analysis made in Caesarean‐delivered subgroup allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (p=0.006), and eczema in 18.9% and 37.5% respectively (p=0.031). In the whole cohort 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs. 14.7% in the placebo group (p=0.013). There was no statistically significant differences discovered between the characteristics of the participating group and the dropout‐group.

Conclusions

Probiotic intervention protected Caesarean‐delivered subgroup from allergic disease and eczema, but not the total cohort.

This article is protected by copyright. All rights reserved.

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Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients

Publication date: Available online 24 November 2018

Source: Archives of Oral Biology

Author(s): Nagore Ambrosio, María José Marín, Estefanía Laguna, David Herrera, Mariano Sanz, Elena Figuero

Abstract

Objective

This study was aimed to compare the presence and amounts of bacteremia induced by interdental brushing in healthy (H) and periodontitis (P) individuals using culture based (direct culture [DC]) and molecular based techniques (real-time quantitative polymerase chain reaction [qPCR]) in a cross-sectional study model.

Materials and Methods

After a full mouth periodontal evaluation, blood samples were taken before and 1 min after professionally-administered interdental tooth brushing. These samples were analyzed by DC and qPCR, targeting Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Subgingival samples were also collected and analyzed. Student t-test, chi-square tests correlations were used for analyzing the data.

Results

Thirty individuals per group were included. P. gingivalis and A. actinomycetemcomitans were detected with qPCR methods, but not with DC. At baseline, bacteremia was observed in 5 P patients (16.7%) and in 2 H individuals (6.6%) (p = 0.421). After interdental tooth brushing, bacteremia was only observed in 2 P patients (6.6%) (p = 0.901). A positive correlation between subgingival and blood levels of A. actinomycetemcomitans was observed (r = 0.3; p = 0.013).

Conclusion

Bacteremia related to A. actinomycetemcomitans and P. gingivalis did not significantly increase after a single session of use of interdental brushes.

https://ift.tt/2KvnR7H

Detection and quantification of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans in bacteremia induced by interdental brushing in periodontally healthy and periodontitis patients

Publication date: Available online 24 November 2018

Source: Archives of Oral Biology

Author(s): Nagore Ambrosio, María José Marín, Estefanía Laguna, David Herrera, Mariano Sanz, Elena Figuero

Abstract

Objective

This study was aimed to compare the presence and amounts of bacteremia induced by interdental brushing in healthy (H) and periodontitis (P) individuals using culture based (direct culture [DC]) and molecular based techniques (real-time quantitative polymerase chain reaction [qPCR]) in a cross-sectional study model.

Materials and Methods

After a full mouth periodontal evaluation, blood samples were taken before and 1 min after professionally-administered interdental tooth brushing. These samples were analyzed by DC and qPCR, targeting Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. Subgingival samples were also collected and analyzed. Student t-test, chi-square tests correlations were used for analyzing the data.

Results

Thirty individuals per group were included. P. gingivalis and A. actinomycetemcomitans were detected with qPCR methods, but not with DC. At baseline, bacteremia was observed in 5 P patients (16.7%) and in 2 H individuals (6.6%) (p = 0.421). After interdental tooth brushing, bacteremia was only observed in 2 P patients (6.6%) (p = 0.901). A positive correlation between subgingival and blood levels of A. actinomycetemcomitans was observed (r = 0.3; p = 0.013).

Conclusion

Bacteremia related to A. actinomycetemcomitans and P. gingivalis did not significantly increase after a single session of use of interdental brushes.

https://ift.tt/2KvnR7H

Extranodal extension is a criterion for poor outcome in patients with metastatic nodes from cancer of the nasopharynx

Publication date: January 2019

Source: Oral Oncology, Volume 88

Author(s): Qi-Yong Ai, Ann D. King, Darren M.C. Poon, Frankie K.F. Mo, Edwin P. Hui, Macy Tong, Anil T. Ahuja, Brigette B.Y. Ma, Anthony T.C. Chan

Abstract

Purpose

Extranodal extension (ENE) is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. Our aim was to determine if ENE should be a staging criterion for nasopharyngeal carcinoma (NPC).

Materials & methods

MRI of 546 NPC patients were reviewed retrospectively and in 404/546 (74.0%) with metastatic nodes, the nodes were assessed for ENE (grade 0 = absent; grade 1 = infiltration of surrounding fat; grade 2 = infiltration of muscle/skin), size (total volume), site (unilateral/bilateral and upper/lower neck) and necrosis. Associations between nodal features and regional relapse free survival (RRFS), distant metastases free survival (DMFS) and overall survival (OS) were assessed using cox regression. Differences of survival rates were compared using log-rank test. A p-value of < 0.05 indicates statistical significance.

Results

ENE grade was the only determinant of RRFS (p = 0.014) and only independent determinant of DMFS (p = 0.003) and OS (p < 0.001). Grade 2 ENE was associated with significantly poorer RRFS, DMFS and OS compared to grade 0 and 1 (p < 0.05). Addition of grade 2 ENE to N1 and N2 disease showed similar poor RRFS, DMFS and OS to N3 disease (p > 0.05). Compared to the current stage N3 disease, inclusion of grade 2 ENE increased the number of N3 patients from 53/546 (9.7%) to 82/546 (15.0%) with similar hazard ratios for DMFS (6.855 and 7.125, respectively) and OS (3.614 and 4.085, respectively).

Conclusion

Grade 2 ENE (into muscle and/or skin and/or salivary glands) is an independent indicator of poor outcome and may be considered as a new criterion for N3 nodal disease in NPC.

https://ift.tt/2RcNflh

Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1

Publication date: January 2019

Source: Oral Oncology, Volume 88

Author(s): Ling-Ying Wei, Jang-Jaer Lee, Chiou-Yueh Yeh, Chia-Ju Yang, Sang-Heng Kok, Jenq-Yuh Ko, Feng-Chiao Tsai, Jean-San Chia

Abstract

Objectives

Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion.

Materials and methods

Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors.

Results

Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1β and CXCR2 are also highly expressed in OSCC and IL-1β mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1β exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs.

Conclusion

The induction of IL-1β following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment.

https://ift.tt/2PQ9rVw

Recurrent Adenomatous Neuroendocrine Tumor of the Middle Ear: A Diagnostic Challenge

Middle ear adenomatous neuroendocrine tumor (MEANT) poses a diagnostic challenge. Clinical symptoms are nonspecific. Definite diagnosis is made by histopathological analysis of the tumor after a complete surgical resection based on an extensive computed tomography/magnetic resonance imaging (CT/MRI). Controversial terminology of the neoplasm arises from the differentiation of this tumor composed of both endocrine and exocrine glands. Middle ear (ME) localization is rare and less aggressive than gastrointestinal tract or lung localizations. Nevertheless, clinical and CT/MRI analyses are necessary follow-ups for preventing or detecting recurrence or metastasis. A case of a female patient aged 26 with recurrent middle ear neuroendocrine adenoma is presented herein.

https://ift.tt/2S6ebTu