Publications by authors named "Luis Caraballo"

87 Publications

Chronic Obstructive Pulmonary Disease Patients Have Increased Levels of Plasma Inflammatory Mediators Reported Upregulated in Severe COVID-19.

Front Immunol 2021 15;12:678661. Epub 2021 Jul 15.

Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.

Background: Chronic obstructive pulmonary disease (COPD) is associated with increased risk of severe COVID-19, but the mechanisms are unclear. Besides, patients with severe COVID-19 have been reported to have increased levels of several immune mediators.

Methods: Ninety-two proteins were quantified in 315 plasma samples from 118 asthmatics, 99 COPD patients and 98 healthy controls (age 40-90 years), who were recruited in Colombia before the COVID-19 pandemic. Protein levels were compared between each disease group and healthy controls. Significant proteins were compared to the gene signatures of SARS-CoV-2 infection reported in the "COVID-19 Drug and Gene Set Library" and with experimentally tested protein biomarkers of severe COVID-19.

Results: Forty-one plasma proteins showed differences between patients and controls. Asthmatic patients have increased levels in IL-6 while COPD patients have a broader systemic inflammatory dysregulation driven by HGF, OPG, and several chemokines (CXCL9, CXCL10, CXCL11, CX3CL1, CXCL1, MCP-3, MCP-4, CCL3, CCL4 and CCL11). These proteins are involved in chemokine signaling pathways related with response to viral infections and some, were found up-regulated upon SARS-CoV-2 experimental infection of Calu-3 cells as reported in the COVID-19 Related Gene Sets database. An increase of HPG, CXCL9, CXCL10, IL-6, MCP-3, TNF and EN-RAGE has also been experimentally detected in patients with severe COVID-19.

Conclusions: COPD patients have altered levels of plasma proteins that have been reported increased in patients with severe COVID-19. Our study suggests that COPD patients have a systemic dysregulation in chemokine networks (including HGF and CXCL9) that could make them more susceptible to severe COVID-19. Also, that IL-6 levels are increased in some asthmatic patients (especially in females) and this may influence their response to COVID-19. The findings in this study depict a novel panel of inflammatory plasma proteins in COPD patients that may potentially associate with increased susceptibility to severe COVID-19 and might be useful as a biomarker signature after future experimental validation.
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http://dx.doi.org/10.3389/fimmu.2021.678661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320593PMC
August 2021

Genotyping of Ascaris spp. infecting humans and pigs in Italy, Slovakia and Colombia.

Infect Genet Evol 2021 Oct 10;94:104997. Epub 2021 Jul 10.

Department of Public Health and Infectious Diseases, Section of Parasitology, Sapienza University of Rome, Rome, Italy. Electronic address:

Background: The systematics and taxonomy of Ascaris lumbricoides and Ascaris suum, two of the world's most widespread nematodes, still represent a highly debated scientific issue. Two different transmission scenarios have been described according to endemicity: separated host-specific transmission cycles in endemic regions, and a single pool of infection shared by humans and pigs in non-endemic regions. The swine roundworm A. suum is now recognized as an important cause of human ascariasis also in endemic areas such as China, where cross-infections and hybridization have also been reported, as well as in non-endemic regions like Italy. This study aimed to investigate the molecular epidemiology of human and pig ascariasis in three countries representing different epidemiological scenarios: Italy as a non-endemic country, Colombia as an endemic country, and Slovakia as a non-endemic country, but with a poor socio-economic context linked to some focal populations of Roma settlements.

Materials And Methods: A total of 237 nematodes were analysed: 46 from Colombia (13 from humans, 33 from pigs), 114 from Slovakia (20 from humans, 94 from pigs) and 77 from Italy (17 from humans and 60 from pigs). Genotyping by PCR-RFLP of nuclear (ITS) and sequencing of mitochondrial (cox1) target regions were performed. ITS genotypes were used to estimate the Hardy-Weinberg (HW) equilibrium according to hosts and country of origin. The partial cox1 sequences were used to analyse genetic polymorphisms according to hosts and country of origin, as well as to infer the network of haplotypes, their evolutionary relationships and geographical distribution.

Results: 110 quality cox1 sequences were obtained. Haplotype network revealed three main groups corresponding to clade A, B and C. Clade C included most of the human cases from Italy, while those from Slovakia and Colombia were grouped in clade B. Ascaris from Italian and Colombian pigs showed HW equilibrium at the ITS marker, while disequilibrium was found in A. lumbricoides from Slovak pigs, which suggest a high unexpected amount of roundworms of human origin circulating also in pigs.

Conclusions: This study updates and extends the current understanding of Ascaris species and genotypes circulating in different epidemiological scenarios, with particular attention to the inclusion of human-derived Ascaris in the phylogenetic cluster C. Despite the evidence of HW equilibrium in the ITS in pig-derived Italian samples, the amount of genetic variation seems to support the existence of two closely related species.
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http://dx.doi.org/10.1016/j.meegid.2021.104997DOI Listing
October 2021

Are the Terms Major and Minor Allergens Useful for Precision Allergology?

Front Immunol 2021 8;12:651500. Epub 2021 Mar 8.

Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.

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http://dx.doi.org/10.3389/fimmu.2021.651500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982392PMC
March 2021

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA LEN consensus.

Allergy 2021 08 14;76(8):2354-2366. Epub 2021 May 14.

Division of Allergy, Department of Pediatric Medicine, The Bambino Gesù Children's Research Hospital Holy see, IRCCS, Rome, Italy.

Background: Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases.

Methods: A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis.

Results: Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001).

Conclusions: This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
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http://dx.doi.org/10.1111/all.14815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250633PMC
August 2021

Perinatal and Early-Life Nutrition, Epigenetics, and Allergy.

Nutrients 2021 Feb 25;13(3). Epub 2021 Feb 25.

Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.
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http://dx.doi.org/10.3390/nu13030724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996340PMC
February 2021

Helminth-derived cystatins: the immunomodulatory properties of an cystatin.

Parasitology 2021 Feb 10:1-13. Epub 2021 Feb 10.

Institute for Immunological Research, University of Cartagena, Cartagena de Indias, Colombia.

Helminth infections such as ascariasis elicit a type 2 immune response resembling that involved in allergic inflammation, but differing to allergy, they are also accompanied with strong immunomodulation. This has stimulated an increasing number of investigations, not only to better understand the mechanisms of allergy and helminth immunity but to find parasite-derived anti-inflammatory products that could improve the current treatments of chronic non-communicable inflammatory diseases such as asthma. A great number of helminth-derived immunomodulators have been discovered and some of them extensively analysed, showing their potential use as anti-inflammatory drugs in clinical settings. Since Ascaris lumbricoides is one of the most successful parasites, several groups have focused on the immunomodulatory properties of this helminth. As a result, several excretory/secretory components and purified molecules have been analysed, revealing interesting anti-inflammatory activities potentially useful as therapeutic tools. One of these molecules is A. lumbricoides cystatin, whose genomic, cellular, molecular, and immunomodulatory properties are described in this review.
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http://dx.doi.org/10.1017/S0031182021000214DOI Listing
February 2021

Allergy and coronavirus disease (COVID-19) international survey: Real-life data from the allergy community during the pandemic.

World Allergy Organ J 2021 Feb 31;14(2):100515. Epub 2021 Jan 31.

Department of Medicine, Allergy Asthma and Clinical Immunology Section, University Hospital of Verona, Verona Italy.

Background: The COVID-19 outbreak brought an unprecedented challenge to the world. Knowledge in the field has been increasing exponentially and the main allergy societies have produced guidance documents for better management of allergic patients during this period. However, few publications so far have provided real-life data from the allergy community concerning allergy practice during the COVID-19 outbreak. Therefore, we proposed an international survey on the management of allergic patients during the current pandemic.

Methods: We performed an online survey undertaken to reach out the worldwide allergy community by e-mail and social media. The web-based questionnaire contained 24 questions covering demographic data from the participants, clinical practice during this period, and questions related to the new international classification and coding tools addressed for COVID-19. It was circulated for 8 weeks and had anonymous and volunteer context.

Results: Data are presented for 635 participants from 78 countries of all continents. Allergists with long-term professional experience were the main audience. As expected, we received many responses as "I have no data" or "I don't know" to the questions of the survey. However, most with more experience on managing allergic patients during the pandemic agreed that patients suffering from allergic or hypersensitivity conditions have no increased risk of contracting COVID-19 or developing SARS CoV-2. Also, participants mentioned that none of the allergy treatments (inhaled corticosteroids, allergen immunotherapy, biological agents) increased the risk of contracting COVID-19 infection including severe presentations.

Conclusion: The data presented are a starting point in the process of getting feedback on all the recommendations provided by the allergy societies; it could also be the basis of new strategies to support health professionals while new COVID-19 specific treatments and vaccines are being explored. The information here presented intends to be helpful to the community but represents a course of action in a highly specific situation due to the state of emergency, and it should be helpful to health systems.
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http://dx.doi.org/10.1016/j.waojou.2021.100515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847410PMC
February 2021

Air pollution and indoor settings.

World Allergy Organ J 2021 Jan 7;14(1):100499. Epub 2021 Jan 7.

UNC School of Medicine, University of North Carolina, Chapel Hill, NC, United States.

Indoor environments contribute significantly to total human exposure to air pollutants, as people spend most of their time indoors. Household air pollution (HAP) resulting from cooking with polluting ("dirty") fuels, which include coal, kerosene, and biomass (wood, charcoal, crop residues, and animal manure) is a global environmental health problem. Indoor pollutants are gases, particulates, toxins, and microorganisms among others, that can have an impact especially on the health of children and adults through a combination of different mechanisms on oxidative stress and gene activation, epigenetic, cellular, and immunological systems. Air pollution is a major risk factor and contributor to morbidity and mortality from major chronic diseases. Children are significantly affected by the impact of the environment due to biological immaturity, prenatal and postnatal lung development. Poor air quality has been related to an increased prevalence of clinical manifestations of allergic asthma and rhinitis. Health professionals should increase their role in managing the exposure of children and adults to air pollution with better methods of care, prevention, and collective action. Interventions to reduce household pollutants may promote health and can be achieved with education, community, and health professional involvement.
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http://dx.doi.org/10.1016/j.waojou.2020.100499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806792PMC
January 2021

Identification and Physicochemical Characterization of a New Allergen from .

Int J Mol Sci 2020 Dec 21;21(24). Epub 2020 Dec 21.

Institute for Immunological Research, University of Cartagena, Cartagena 130014, Colombia.

To analyze the impact of infection on the pathogenesis and diagnosis of allergic diseases, new allergens should be identified. We report the identification of a new allergen, Asc l 5. The aim of this study was to evaluate the physicochemical and immunological features of the Asc l 5 allergen. We constructed an cDNA library and Asc l 5 was identified by immunoscreening. After purification, rAsc l 5 was physicochemically characterized. Evaluation of its allergenic activity included determination of Immunoglobulin E (IgE) binding frequency (in two populations: 254 children and 298 all-age subjects), CD203c based-basophil activation tests (BAT) and a passive cutaneous anaphylaxis (PCA) mouse model. We found by amino acid sequence analysis that Asc l 5 belongs to the SXP/RAL-2 protein family of nematodes. rAsc l 5 is a monomeric protein with an alpha-helical folding. IgE sensitization to rAsc l 5 was around 52% in general population; positive BAT rate was 60%. rAsc l 5 induced specific IgE production in mice and a positive PCA reaction. These results show that Asc l 5 has structural and immunological characteristics to be considered as a new allergen from .
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http://dx.doi.org/10.3390/ijms21249761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767342PMC
December 2020

Serum amyloid A is a soluble pattern recognition receptor that drives type 2 immunity.

Nat Immunol 2020 07 22;21(7):756-765. Epub 2020 Jun 22.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

The molecular basis for the propensity of a small number of environmental proteins to provoke allergic responses is largely unknown. Herein, we report that mite group 13 allergens of the fatty acid-binding protein (FABP) family are sensed by an evolutionarily conserved acute-phase protein, serum amyloid A1 (SAA1), that promotes pulmonary type 2 immunity. Mechanistically, SAA1 interacted directly with allergenic mite FABPs (Der p 13 and Blo t 13). The interaction between mite FABPs and SAA1 activated the SAA1-binding receptor, formyl peptide receptor 2 (FPR2), which drove the epithelial release of the type-2-promoting cytokine interleukin (IL)-33 in a SAA1-dependent manner. Importantly, the SAA1-FPR2-IL-33 axis was upregulated in nasal epithelial cells from patients with chronic rhinosinusitis. These findings identify an unrecognized role for SAA1 as a soluble pattern recognition receptor for conserved FABPs found in common mite allergens that initiate type 2 immunity at mucosal surfaces.
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http://dx.doi.org/10.1038/s41590-020-0698-1DOI Listing
July 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

Dept of Otorhinolaryngology, Chiba University Hospital, Chiba, Japan.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

COVID-19, asthma, and biological therapies: What we need to know.

World Allergy Organ J 2020 May 16;13(5):100126. Epub 2020 May 16.

Department of Otolaryngology-Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon.

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV-2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID-19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers.
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http://dx.doi.org/10.1016/j.waojou.2020.100126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229954PMC
May 2020

IgE Levels to and House Dust Mite Allergens Are Associated With Increased Histone Acetylation at Key Type-2 Immune Genes.

Front Immunol 2020 28;11:756. Epub 2020 Apr 28.

Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.

Background: Epigenetic changes in response to allergen exposure are still not well understood. The aim of this study was to evaluate histone acetylation levels in peripheral blood leukocytes from humans naturally infected by intestinal parasites and perennially exposed to house dust mites (HDM).

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated by gradient centrifugation from 20 infected and 21 non-infected individuals living in a rural/village in Colombia. Histone 3 acetylation (H3Ac) and histone 4 acetylation (H4Ac) levels were measured in six immune genes previously associated with helminth immunity by chromatin immunoprecipitation (ChIP)-quantitative PCR. Then we analyzed the association between histone acetylation levels with total parasite egg burden and IgE levels.

Results: We found an inverse correlation between H4Ac levels in the gene and egg worm burden that remained significant after adjustment by age [-0.20 (-0.32 to -0.09), < 0.0001]. Moreover, we found significant associations between H4Ac levels in [0.32 (0.05-0.60), = 0.02] and [0.29 (0.08-0.51), = 0.008] with the IgE levels to . In addition, the levels of specific IgE antibodies to HDM were associated with H4Ac levels in the gene encoding the B cell activating factor (BAFF) [0.51 (0.26-0.76), < 0.001]. All values are presented as beta (95% CI).

Conclusion: Histone acetylation levels at key type-2 immune genes in humans were modified by nematode infection and HDM allergens and are associated with the intensity of the IgE response.
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http://dx.doi.org/10.3389/fimmu.2020.00756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204827PMC
March 2021

The allergenic activity and clinical impact of individual IgE-antibody binding molecules from indoor allergen sources.

World Allergy Organ J 2020 May 29;13(5):100118. Epub 2020 Apr 29.

Department of Clinical Immunology and Allergy, Laboratory of Immunopathology, Sechenov First Moscow State Medical University, Moscow, Russia.

A large number of allergens have been discovered but we know little about their potential to induce inflammation (allergenic activity) and symptoms. Nowadays, the clinical importance of allergens is determined by the frequency and intensity of their IgE antibody binding (allergenicity). This is a rather limited parameter considering the development of experimental allergology in the last 20 years and the criteria that support personalized medicine. Now it is known that some allergens, in addition to their IgE antibody binding properties, can induce inflammation through non IgE mediated pathways, which can increase their allergenic activity. There are several ways to evaluate the allergenic activity, among them the provocation tests, the demonstration of non-IgE mediated pathways of inflammation, case control studies of IgE-binding frequencies, and animal models of respiratory allergy. In this review we have explored the current status of basic and clinical research on allergenic activity of indoor allergens and confirm that, for most of them, this important property has not been investigated. However, during recent years important advances have been made in the field, and we conclude that for at least the following, allergenic activity has been demonstrated: Der p 1, Der p 2, Der p 5 and Blo t 5 from HDMs; Per a 10 from ; Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6 from ; Mala s 8 and Mala s 13 from ; Alt a 1 from ; Pen c 13 from ; Fel d 1 from cats; Can f 1, Can f 2, Can f 3, Can f 4 and Can f 5 from dogs; Mus m 1 from mice and Bos d 2 from cows. Defining the allergenic activity of other indoor IgE antibody binding molecules is necessary for a precision-medicine-oriented management of allergic diseases.
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http://dx.doi.org/10.1016/j.waojou.2020.100118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195550PMC
May 2020

Liver failure due to relapsed myeloma and hepatic iron overload.

Ecancermedicalscience 2020 30;14:1028. Epub 2020 Apr 30.

Department of Pathology, Cleveland Clinic Florida, Weston, Florida, USA.

Multiple myeloma is a hematologic malignancy that classically manifests with hypercalcaemia, renal insufficiency, anaemia and lytic bone lesions. Liver dysfunction in multiple myeloma is a lesser known complication that occurs through biliary obstruction, liver infiltration by plasma cells, amyloid/light chain deposition or due to liver injury from medications. Although transfusion-related hepatic iron overload-leading to significant liver disease-is a recognised complication in certain hematologic malignancies, little is known about transfusional iron overload in patients with multiple myeloma. We present a case of a 49-year-old female with relapsed/refractory multiple myeloma who presented with rapid onset liver failure, due to both iron deposition and malignant plasma cell infiltration of the liver as a terminal event. A review of the literature on hepatic complications in multiple myeloma patients is presented.
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http://dx.doi.org/10.3332/ecancer.2020.1028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192399PMC
April 2020

International expert consensus on the management of allergic rhinitis (AR) aggravated by air pollutants: Impact of air pollution on patients with AR: Current knowledge and future strategies.

World Allergy Organ J 2020 Mar 3;13(3):100106. Epub 2020 Apr 3.

Department of Otolaryngology- Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon.

Allergic rhinitis affects the quality of life of millions of people worldwide. Air pollution not only causes morbidity, but nearly 3 million people per year die from unhealthy indoor air exposure. Furthermore, allergic rhinitis and air pollution interact. This report summarizes the discussion of an International Expert Consensus on the management of allergic rhinitis aggravated by air pollution. The report begins with a review of indoor and outdoor air pollutants followed by epidemiologic evidence showing the impact of air pollution and climate change on the upper airway and allergic rhinitis. Mechanisms, particularly oxidative stress, potentially explaining the interactions between air pollution and allergic rhinitis are discussed. Treatment for the management of allergic rhinitis aggravated by air pollution primarily involves treating allergic rhinitis by guidelines and reducing exposure to pollutants. Fexofenadine a non-sedating oral antihistamine improves AR symptoms aggravated by air pollution. However, more efficacy studies on other pharmacological therapy of coexisting AR and air pollution are currently lacking.
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http://dx.doi.org/10.1016/j.waojou.2020.100106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132263PMC
March 2020

IgE allergy diagnostics and other relevant tests in allergy, a World Allergy Organization position paper.

World Allergy Organ J 2020 Feb 25;13(2):100080. Epub 2020 Feb 25.

University of South Florida College of Medicine, Tampa, FL, USA.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both and . It discusses skin tests, challenges, and serological and cellular tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen.
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http://dx.doi.org/10.1016/j.waojou.2019.100080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7044795PMC
February 2020

Toward personalization of asthma treatment according to trigger factors.

J Allergy Clin Immunol 2020 06 18;145(6):1529-1534. Epub 2020 Feb 18.

Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden; Department of Womenś and Children's Health, Karolinska Institutet, Stockholm, Sweden.

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
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http://dx.doi.org/10.1016/j.jaci.2020.02.001DOI Listing
June 2020

Personalized medicine for asthma in tropical regions.

Curr Opin Allergy Clin Immunol 2020 06;20(3):268-273

Institute for Immunological Research, University of Cartagena, Cartagena, Colombia.

Purpose Of Review: Precision medicine could help to improve diagnosis and treatment of asthma; however, in the tropics there are special conditions to be considered for applying this strategy. In this review, we analyze recent advances of precision allergology in tropical regions, highlighting its limitations and needs in high-admixed populations living under environments with high exposure to house dust mites and helminth infections.

Recent Findings: Advances have been made regarding the genetic characterization of the great diversity of populations living in the tropics. Genes involved in shared biological pathways between immune responses to nematodes and the allergic responses suggested new mechanisms of predisposition. Genome wide association studies of asthma are progressively focusing on some highly replicated genes such as those in chromosome 17q31-13, which have been also replicated in African ancestry populations. Some diagnostic difficulties, because of the endemicity of helminth infections, are now more evident in the context of phenotype definition.

Summary: The clinical impact of the advances in precision medicine for asthma in the tropics is still limited and mainly related to component resolved diagnosis. More basic and clinical research is needed to identify genetic, epigenetic, or other biologic markers that allow and accurate definition of phenotypes and endotypes of this heterogeneous disease. This will substantially improve the selection of personalized treatments.
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http://dx.doi.org/10.1097/ACI.0000000000000628DOI Listing
June 2020

Identification of B Cell Epitopes of Blo t 13 Allergen and Cross-Reactivity with Human Adipocytes and Heart Fatty Acid Binding Proteins.

Int J Mol Sci 2019 Dec 4;20(24). Epub 2019 Dec 4.

Institute for Immunological Research, University of Cartagena, Cartagena 130000, Colombia.

Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite , which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.
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http://dx.doi.org/10.3390/ijms20246107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940925PMC
December 2019

Next-generation Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines for allergic rhinitis based on Grading of Recommendations Assessment, Development and Evaluation (GRADE) and real-world evidence.

J Allergy Clin Immunol 2020 01 15;145(1):70-80.e3. Epub 2019 Oct 15.

ProAR-Nucleo de Excelencia em Asma, Federal University of Bahia, and the WHO GARD Planning Group, Bahia, Brazil.

The selection of pharmacotherapy for patients with allergic rhinitis aims to control the disease and depends on many factors. Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines have considerably improved the treatment of allergic rhinitis. However, there is an increasing trend toward use of real-world evidence to inform clinical practice, especially because randomized controlled trials are often limited with regard to the applicability of results. The Contre les Maladies Chroniques pour un Vieillissement Actif (MACVIA) algorithm has proposed an allergic rhinitis treatment by a consensus group. This simple algorithm can be used to step up or step down allergic rhinitis treatment. Next-generation guidelines for the pharmacologic treatment of allergic rhinitis were developed by using existing GRADE-based guidelines for the disease, real-world evidence provided by mobile technology, and additive studies (allergen chamber studies) to refine the MACVIA algorithm.
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http://dx.doi.org/10.1016/j.jaci.2019.06.049DOI Listing
January 2020

Cystatin Prevents Development of Allergic Airway Inflammation in a Mouse Model.

Front Immunol 2019 27;10:2280. Epub 2019 Sep 27.

Institute for Immunological Research, Universidad de Cartagena, Cartagena, Colombia.

Severe helminth infections are negatively associated to allergic diseases like asthma; therefore, the immunomodulatory properties of parasite-derived components have been analyzed, raising the possibility of their use as anti-inflammatory molecules. We evaluated the immunomodulatory properties of recombinant cysteine protease inhibitor (rAl-CPI) in a mouse model of allergic airway inflammation induced by the house dust mite (HDM) and its effects on human monocyte-derived dendritic cells (HmoDCs). The sensitized/challenged mice developed extensive cellular airway inflammatory response, which was significantly reduced upon treatment with rAl-CPI prior to sensitization, affecting particularly the perivascular/peribronchial infiltrate cells, eosinophils/neutrophils, and goblet cells. A significant decrease of Th2 cytokines, total, and specific IgE antibodies was observed in rAl-CPI treated mice. The antibody response was biased to IgG, mainly IgG2a. Administration of rAl-CPI-alone and rAl-CPI before mite sensitization were associated with a significant increase of regulatory T cells (Tregs) in spleen and elevated IL-10 levels in BAL and splenocytes culture supernatants, which was partially affected by anti-IL10 receptor use. , rAl-CPI showed a modulatory effect on HmoDCs, lowering the expression of HLA-DR, CD83, and CD86, while inducing IL-10 and IL-6 production. This suggests an inhibition of HmoDC maturation and a possible link with the inhibition of the allergic response observed in the murine model.
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http://dx.doi.org/10.3389/fimmu.2019.02280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777510PMC
October 2020

The Striking Appearance of a Rare Skin Condition: "Half-Half" Blisters (Subcorneal Pustular Dermatosis).

J Allergy Clin Immunol Pract 2020 Feb 11;8(2):732-733. Epub 2019 Oct 11.

Center for Medical Specialties, Department of Allergy and Immunology, Cleveland Clinic, Weston, Fla.

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http://dx.doi.org/10.1016/j.jaip.2019.09.018DOI Listing
February 2020

An Engineered Hybrid Protein from Allergens Shows Hypoallergenicity.

Int J Mol Sci 2019 Jun 21;20(12). Epub 2019 Jun 21.

Institute for Immunological Research, University of Cartagena, Cartagena 130000, Colombia.

The house dust mite (HDM) is an important risk factor for asthma and rhinitis. Allergen specific immunotherapy that is based on recombinant proteins has been proposed for the safer and more efficient treatment of allergic diseases. The aim of this study was to design and obtain a hybrid protein (DPx4) containing antigenic regions of allergens Der p 1, Der p 2, Der p 7, and Der p 10 from this mite. DPx4 was produced in and its folding was determined by circular dichroism. Non-denaturing dot-blot, ELISA, basophil activation test, dot blot with monoclonal antibodies, ELISA inhibition, and cysteine protease activity assays were performed. Mice that were immunized with DPx4 were also analyzed. We found that DPx4 had no cysteine protease activity and it showed significantly lower IgE reactivity than Der p 1, Der p 2, and extract. DPx4 induced lower basophil activation than Der p 2 and the allergen extract. Immunized mice produced IgG antibodies that inhibited the binding of allergic patient's IgE to the allergen extract and induced comparatively higher levels of IL-10 than the extract in peripheral blood mononuclear cells (PBMC) culture. These results suggest that DPx4 has immunological properties that are useful for the development of a mite allergy vaccine.
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http://dx.doi.org/10.3390/ijms20123025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628193PMC
June 2019
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