Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 403121, 9 pages
http://dx.doi.org/10.1155/2013/403121

Review Article

Human Monoclonal Antibody-Based Therapy in the Treatment of Invasive Candidiasis

Francesca Bugli, Margherita Cacaci, Cecilia Martini, Riccardo Torelli,Brunella Posteraro, Maurizio Sanguinetti, and Francesco Paroni Sterbini

Institute of Microbiology, Università Cattolica del Sacro Cuore, Rome, Italy

Received 14 May 2013; Accepted 13 June 2013

Academic Editor: Roberto Burioni

Copyright © 2013 Francesca Bugli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Invasive candidiasis (IC) represents the leading fungal infection of humans causing life-threatening disease in immunosuppressed and neutropenic individuals including also the intensive care unit patients. Despite progress in recent years in drugs development for the treatment of IC, morbidity and mortality rates still remain very high. Historically, cell-mediated immunity and innate immunity are considered to be the most important lines of defense against candidiasis. Nevertheless recent evidence demonstrates that antibodies with defined specificities could act with different degrees showing protection against systemic and mucosal candidiasis. Mycograb is a human recombinant monoclonal antibody against heat shock protein 90 (Hsp90) that was revealed to have synergy when combined with fluconazole, caspofungin, and amphotericin B against a broad spectrum of Candida species. Furthermore, recent studies have established an important role for Hsp90 in mediating Candidaresistance to echinocandins, giving to this antibody molecule even more attractive biological properties. In response to the failure of marketing authorization by the CHMP (Committee for Medicinal Products for Human Use) a new formulation of Mycograb, named Mycograb C28Y variant, with an amino acid substitution was developed in recent years. First data on Mycograb C28Y variant indicate that this monoclonal antibody lacked efficacy in a murine candidiasis model.

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• PLoS One
• v.8(6); 2013
• PMC3680455

PLoS One. 2013; 8(6): e66040.

Published online 2013 June 12. doi:  10.1371/journal.pone.0066040

PMCID: PMC3680455

The Observed Association between Maternal Anxiety and Adolescent Asthma: Children of Twin Design Suggest Familial Effects

Ida Havland,1 Cecilia Lundholm,1 Paul Lichtenstein,1 Jenae M. Neiderhiser,2 Jody M. Ganiban,3 Erica L. Spotts,4Hasse Walum,1 David Reiss,5 and Catarina Almqvist1,6,*

Susanne Krauss-Etschmann, Editor

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Abstract

Background

Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear.

Objective

To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors).

Method

From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association.

Results

Maternal BAI anxiety (OR 2.02, CI 1.15–3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04–2.91) and psychic anxiety (OR 1.74, CI 1.05–2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding.

Conclusions

We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.

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Int J Appl Basic Med Res. 2011 Jan-Jun; 1(1): 20–23.

doi:  10.4103/2229-516X.81975

PMCID: PMC3657951

Acceptable alternatives for forced vital capacity in the spirometric diagnosis of bronchial asthma

Mohamed Faisal Lutfi

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This article has been corrected. See Int J Appl Basic Med Res. 2012; 2(1): 62.

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Abstract

Background:

In patients with advanced obstructive ventilatory disorders, expiration may last for a relatively long time until the end-of-test standards for forced vital capacity (FVC) are satisfied. This may be difficult for both the patient and the technician. The Forced expiratory volume in 3 seconds (FEV3) and Forced expiratory volume in 6 seconds (FEV6) maneuvers are simple, undemanding and easier to perform when compared with FVC; however, their reliability to be used as alternatives for FVC is controversial.

Aim:

To judge whether FEV3 and FEV6 can be used instead of FVC in detecting airway obstruction in asthmatic patients.

Settings and Design:

This study was a cross-sectional case–control laboratory-based study.

Materials and Methods:

The study involved 40 known asthmatic patients and 40 apparently healthy, gender- and age-matched controls. Spirometery was used for assessing pulmonary function according to the American Thoracic Society and European Respiratory Society criteria.

Statistical Analysis:

A significant difference in the means between the groups was performed using Student's t-test. The receiver operating characteristic (ROC) curves were used to compare efficiency of the studied spirometric measurements on asthma diagnosis.

Results:

The mean of FEV3 was not significantly different when compared with the mean of FVC (P = 0.352 for asthmatic patients and P = 0.957 for control group). This was also true when the mean of FEV6 was compared with the mean of FVC (P = 0.805 for asthmatic patients and P = 0.957 for control group). The area under the ROC curves of FEV1/FVC%, FEV1/FEV3% and FEV1/FEV6% were also comparable.

Conclusion:

FEV3 and FEV6 are accurate and reliable alternatives for FVC in assessing airway obstruction of asthmatic patients.

Keywords: Asthma, end-of-test, FVC, FEV3, FEV6, lung function tests

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Journal of Asthma and Allergy

Racial differences in the association of CD14 polymorphisms with serum total IgE levels and allergen skin test reactivity

Original Research

(29) Total Article Views

Authors: Wang ZY, Sundy JS, Foss CM, Barnhart HX, Palmer SM, Allgood SD, Trudeau E, Alexander KM, Levesque MC

Published Date June 2013 Volume 2013:6 Pages 81 - 92

DOI: http://dx.doi.org/10.2147/JAA.S42695

Received:	12 January 2013
Accepted:	08 April 2013
Published:	25 June 2013

ZongYao Wang,¹ John S Sundy,¹ Catherine M Foss,¹ Huiman X Barnhart,² Scott M Palmer,¹ Sallie D Allgood,³ Evan Trudeau,¹ Katie M Alexander,³ Marc C Levesque^3
1Division of Pulmonary, Allergy and Critical Care Medicine, ²Duke Clinical Research Institute,³Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USA

Background: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects.
Methods: A total of 291 participants, 18–40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects.
Results: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans.
Conclusion: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.

Keywords: total serum immunoglobulin E, IgE, skin prick test, SPT, CD14-159T, single nucleotide polymorphism, SNP, lipopolysaccharide, LPS, endotoxin



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Increased Risk of RSV Infection in Children with Down's Syndrome: Clinical Implementation of Prophylaxis in the European Union

Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 801581, 6 pages
http://dx.doi.org/10.1155/2013/801581

Research Article

Increased Risk of RSV Infection in Children with Down's Syndrome: Clinical Implementation of Prophylaxis in the European Union

Dianne van Beek,¹ Bosco Paes,² and Louis Bont^1,3

¹Department of Immunology, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands
²Department of Pediatrics (Neonatal Division), McMaster University, Hamilton, ON, L8S 4L8, Canada
³Division of Infectious Diseases, Department of Pediatrics, University Medical Centre Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands

Received 26 March 2013; Accepted 13 June 2013

Academic Editor: Roberto Burioni

Copyright © 2013 Dianne van Beek et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Prospective cohort studies show that Down’s syndrome (DS) is an independent risk factor for hospitalization for RSV bronchiolitis. It is unknown whether this observation has been translated into specific management for DS children. The primary goal was to assess the knowledge of healthcare providers in the European Union about RSV infection in DS children and to determine whether it influenced the implementation of prophylaxis. DS caregivers were surveyed using a standardized questionnaire, and country-specific guidelines were obtained. Fifty-three caregivers participated. Thirty-nine (86.7%) had knowledge of the increased risk of severe RSV infection in DS children, and 30 (71.4%) graded that it was important to have a statement on the use of RSV prophylaxis in existing guidelines. Twenty-eight participants had a local DS guideline; hard copies of twelve unique guidelines were obtained. Only one (8.3%) contained a statement on RSV prophylaxis for DS, and five considered such a statement for the next version. Conclusion. Most pediatricians had knowledge that DS children have an increased risk of severe RSV infection. Despite the lack of a specific RSV prophylaxis trial in DS, they felt that a statement on RSV prophylaxis in DS guidelines was important, but this was rarely present in current guidelines.

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Research article

Obesity increases eosinophil activity in asthmatic children and adolescents

Milena B Grotta^1*, Dalize M Squebola-Cola², Adyleia ADC Toro¹, Maria Angela GO Ribeiro¹,Silvia B Mazon¹, Jose D Ribeiro¹ and Edson Antunes²

• *Corresponding author: Milena B Grotta milgrotta@hotmail.com

Author Affiliations

¹Paediatric, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil

²Pharmacology Department, State University of Campinas (UNICAMP), Campinas, São Paulo, Brazil

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BMC Pulmonary Medicine 2013, 13:39 doi:10.1186/1471-2466-13-39

The electronic version of this article is the complete one and can be found online at:http://www.biomedcentral.com/1471-2466/13/39

Received:	1 November 2012
Accepted:	10 June 2013
Published:	18 June 2013

© 2013 Grotta et al.; licensee BioMed Central Ltd. 

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

A clear relationship between asthma and obesity has been reported, but the mechanisms remain unclear. The aim of this study was to evaluate the influence of obesity on eosinophil activity (chemotaxis and adhesion) in asthmatic children and adolescents compared with cells from healthy volunteers.

Methods

Asthmatic obese (AO), asthmatic non-obese (ANO), non-asthmatic obese (NAO) and non-asthmatic non-obese (NANO) individuals were included in the present study. The chemotaxis of eosinophils after stimulation with eotaxin (300 ng/ml), platelet-activating factor (10 μM; PAF) and RANTES (100 ng/ml) was performed using a microchemotaxis chamber. The eosinophil peroxidase activity was measured to determine the adhesion activity of eosinophils cultivated on fibronectin-coated plates. The serum leptin, adiponectin, TNF-α and IgE levels were quantified using ELISA assays.

Results

The serum IgE levels and eosinophil counts were significantly higher in asthmatic (obese and non-obese) individuals compared with non-asthmatic individuals (obese and non-obese). Spontaneous eosinophil chemotaxis was greater in the AO group compared with either the ANO or NANO groups. The activation of eosinophils using eotaxin and PAF increased eosinophil chemotaxis in the AO group. RANTES treatment increased eosinophil chemotaxis in the NAO group compared with the NANO or ANO groups. The activation of eosinophils using eotaxin significantly increased eosinophil adhesion in the AO group compared with other groups. The serum leptin and TNF-α levels were higher in obese subjects (asthmatic and non-asthmatic), whereas the levels of adiponectin did not significantly differ among these groups.

Conclusion

This study is the first to show increased eosinophilic activity (chemotaxis and adhesion) associated with high serum leptin and TNF-α levels in atopic asthmatic obese children and adolescents compared with non-obese healthy volunteers.

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Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma.

Mediators of Inflammation
Volume 2013 (2013), Article ID 808470, 11 pages
http://dx.doi.org/10.1155/2013/808470

Research Article

Differential Regulation of Inflammation and Immunity in Mild and Severe Experimental Asthma

Seil Sagar,^1,2 Kim A. T. Verheijden,¹ Niki A. Georgiou,² Johan Garssen,^1,2 Aletta D. Kraneveld,¹ Arjan P. Vos,² and Gert Folkerts¹

¹Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands
²Danone Research, Centre for Specialised Nutrition, 6704 PH Wageningen, The Netherlands

Received 14 January 2013; Revised 15 March 2013; Accepted 4 April 2013

Academic Editor: Alex Kleinjan

Copyright © 2013 Seil Sagar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study aimed at exploring innate and adaptive immunity in allergic asthma by investigation of mRNA expression of pattern recognition receptors, T-cell-specific cytokines, and transcription factors. Mouse models for mild and severe asthma, with similar pathological characteristics observed in humans, were used to study the involved inflammatory markers as a first step in the development of phenotype-directed treatment approaches. In the mild model, mice were sensitized to ovalbumin-Imject Alum and challenged with ovalbumin. In the severe model, mice were sensitized to trinitrophenyl-conjugated ovalbumin and challenged with trinitrophenyl-ovalbumin/IgE immune complex. Pulmonary airway inflammation and mRNA expression of Toll-like receptors (TLRs), NOD-like receptors (NLRs), T cell cytokines, and transcription factors in lung tissue were examined. Different mRNA expression profiles of TLRs, NLRs, T cell cytokines, and transcription factors were observed. In the mild model, Il10showed the largest increase in expression, whereas in the severe model, it was Infγ with the largest increase. Expression of Tbet was also significantly increased in the severe model. Inflammation and immunity are differentially regulated in mild and severe experimental asthma. This preclinical data may help in directing clinical research towards a better understanding and therapy in mild and severe asthmatic patients.

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Research article

Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy

Gabriel J Escobar, Anthony S Masaquel, Sherian X Li, Eileen M Walsh and Patricia Kipnis

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BMC Pediatrics 2013, 13:97 doi:10.1186/1471-2431-13-97

Published: 19 June 2013

Abstract (provisional)

Background

Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing.

Methods

A retrospective cohort study examined children born at >=32 weeks gestation between 1996--2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions.

Results

The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32--33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03--1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49--4.50).

Conclusions

Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

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