Cystatin from the helminth Ascaris lumbricoides upregulates mevalonate and cholesterol biosynthesis pathways and immunomodulatory genes in human monocyte-derived dendritic cells.

Background: Ascaris lumbricoides cystatin (Al-CPI) prevents the development of allergic airway inflammation and dextran-induced colitis in mice models. It has been suggested that helminth-derived cystatins inhibit cathepsins in dendritic cells (DC), but their immunomodulatory mechanisms are unclear. We aimed to analyze the transcriptional profile of human monocyte-derived DC (moDC) upon stimulation with Al-CPI to elucidate target genes and pathways of parasite immunomodulation. Methods: moDC were generated from peripheral blood monocytes from six healthy human donors of Denmark, stimulated with 1 µM of Al-CPI, and cultured for 5 hours at 37°C. RNA was sequenced using TrueSeq RNA libraries and the NextSeq 550 v2.5 (75 cycles) sequencing kit (Illumina, Inc). After QC, reads were aligned to the human GRCh38 genome using Spliced Transcripts Alignment to a Reference (STAR) software. Differential expression was calculated by DESEq2 and expressed in fold changes (FC). Cell surface markers and cytokine production by moDC were evaluated by flow cytometry. Results: Compared to unstimulated cells, Al-CPI stimulated moDC showed differential expression of 444 transcripts (|FC| ≥1.3). The top significant differences were in Kruppel-like factor 10 (KLF10, FC 3.3, PBH = 3 x 10-136), palladin (FC 2, PBH = 3 x 10-41), and the low-density lipoprotein receptor (LDLR, FC 2.6, PBH = 5 x 10-41). Upregulated genes were enriched in regulation of cholesterol biosynthesis by sterol regulatory element-binding proteins (SREBP) signaling pathways and immune pathways. Several genes in the cholesterol biosynthetic pathway showed significantly increased expression upon Al-CPI stimulation, even in the presence of lipopolysaccharide (LPS). Regarding the pathway of negative regulation of immune response, we found a significant decrease in the cell surface expression of CD86, HLA-DR, and PD-L1 upon stimulation with 1 µM Al-CPI. Conclusion: Al-CPI modifies the transcriptome of moDC, increasing several transcripts encoding enzymes involved in cholesterol biosynthesis and SREBP signaling. Moreover, Al-CPI target several transcripts in the TNF-alpha signaling pathway influencing cytokine release by moDC. In addition, mRNA levels of genes encoding KLF10 and other members of the TGF beta and the IL-10 families were also modified by Al-CPI stimulation. The regulation of the mevalonate pathway and cholesterol biosynthesis suggests new mechanisms involved in DC responses to helminth immunomodulatory molecules.

Risk calculator of the clinical response to antihistamines in chronic urticaria: Development and internal validation.

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.

Comparison of Antibody Responses against Two Molecules from Ascaris lumbricoides: The Allergen Asc l 5 and the Immunomodulatory Protein Al-CPI.

Immunity to Ascaris lumbricoides influences the pathogenesis of allergic diseases. Antibody responses to its proteins have been found to be associated with asthma presentation; however, helminth products that induce immunosuppression have been reported, which also raise specific antibodies. We aimed to evaluate antibody responses (IgE, IgG4 and IgG) to two A. lumbricoides molecules, Asc l 5 and Al-CPI (an anti-inflammatory Cysteine Protease Inhibitor), in an endemic population, exploring their relationships with the infection and asthma. The two molecules were produced as recombinant proteins in E. coli expression systems. Specific antibodies were detected by ELISA. Lower human IgE, but higher IgG4 and IgG antibody levels were observed for Al-CPI than for rAsc l 5. The IgE/IgG4 isotype ratio was significantly higher for Asc l 5 than for Al-CPI. In humans Al-CPI did not induce basophil activation as has been previously described for Asc l 5. In mice, Al-CPI induced fewer IgE responses, but more IgG2a antibody titers than rAsc l 5. Our results suggest that these molecules elicit different patterns of immune response to A. lumbricoides.

Frequent IgE recognition of Blomia tropicalis allergen molecules in asthmatic children and young adults in equatorial Africa.

Background: Asthma is not well investigated in equatorial Africa and little is known about the disease-associated allergen molecules recognized by IgE from patients in this area. The aim was to study the molecular IgE sensitization profile of asthmatic children and young adults in a semi-rural area (Lambaréné) of an equatorial African country (Gabon), to identify the most important allergen molecules associated with allergic asthma in equatorial Africa. Methods: Fifty-nine asthmatic patients, mainly children and few young adults, were studied by skin prick testing to Dermatophagoides pteronyssinus (Der p), D. farinae (Der f), cat, dog, cockroach, grass, Alternaria and peanut. Sera were obtained from a subset of 35 patients, 32 with positive and 3 with negative skin reaction to Der p and tested for IgE reactivity to 176 allergen molecules from different allergen sources by ImmunoCAP ISAC microarray technology and to seven recombinant Blomia tropicalis (Blo t) allergens by IgE dot blot assay. Results: Thirty-three of the 59 patients (56%) were sensitized to Der p and 23 of them (39%) were also sensitized to other allergen sources, whereas 9 patients (15%) were only sensitized to allergen sources other than Der p. IgE serology analyses (n=35) showed high IgE-binding frequencies to the Blo t allergens Blo t 5 (43%), Blo t 21 (43%) and Blo t 2 (40%), whereas the Der p allergens rDer p 2, rDer p 21 and rDer p 5 (34%, 29% and 26%) were less frequently recognized. Only few patients showed IgE reactivity to allergens from other allergen sources, except to allergens containing carbohydrate determinants (CCDs) or to wasp venom allergens (i.e., antigen 5). Conclusion: Our results thus demonstrate that IgE sensitization to mite allergens is very prevalent in asthmatics in Equatorial Africa with B. tropicalis allergen molecules representing the most important ones associated with allergic asthma.

Burden of COVID-19 in Córdoba, A Department of Colombia: Results of Disability-Adjusted Life-Years: Carga de COVID-19 en Córdoba, un Departamento de Colombia: Resultados de los Años de Vida Ajustados por Discapacidad.

OBJECTIVES: This study aimed to estimate the burden of acute COVID-19 in Córdoba, one of the most affected departments (states) in Colombia, through the estimation of disability-adjusted life-years (DALYs). METHODS: DALYs were estimated based on the number of cases of severe acute respiratory syndrome coronavirus 2 infection cases reported by official Colombian sources. A transition probability matrix among severity states was calculated using data obtained from a retrospective cohort that included 1736 COVID-19 confirmed subjects living in Córdoba. RESULTS: Córdoba had 120.23 deaths per 100 000 habitants during the study period (March 2020 to April 2021). Estimated total DALYs were 49 243 (2692 DALYs per 100 000 inhabitants), mostly attributed to fatal cases (99.7%). On average, 25 years of life were lost because of death by this infection. A relevant proportion of years of life lost because of COVID-19 (46.6%) was attributable to people < 60 years old and was greater in men. People ≥ 60 years old showed greater risk of progression to critical state than people between the age of 35 and 60 years (hazard ratio 2.5; 95% confidence interval 2.5-12.5) and younger than 35 years (9.1; 95% confidence interval 4.0-20.6). CONCLUSION: In Córdoba, premature mortality because of COVID-19 was substantially represented by people < 60 years old and was greater in males. Our data may be representative of Latin American populations with great infection spread during the first year of the pandemic and contribute to novel methodological aspects and parameter estimations that may be useful to measure COVID-19 burden in other countries of the region.

The Allergenic Activity of Blo t 2, a Blomia tropicalis IgE-Binding Molecule.

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli. Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.

The hybrid protein BTH2 suppresses allergic airway inflammation in a murine model of HDM-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.

Environmental contributions to the interactions of COVID-19 and asthma: A secondary publication and update.

An outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) started in Wuhan, Hubei Province, China and quickly spread around the world. Current evidence is contradictory on the association of asthma with COVID-19 and associated severe outcomes. Type 2 inflammation may reduce the risk for severe COVID-19. Whether asthma diagnosis may be a risk factor for severe COVID-19, especially for those with severe disease or non-allergic phenotypes, deserves further attention and clarification. In addition, COVID-19 does not appear to provoke asthma exacerbations, and asthma therapeutics should be continued for patients with exposure to COVID-19. Changes in the intensity of pollinization, an earlier start and extension of the pollinating season, and the increase in production and allergenicity of pollen are known direct effects that air pollution has on physical, chemical, and biological properties of the pollen grains. They are influenced and triggered by meteorological variables that could partially explain the effect on COVID-19. SARS-CoV-2 is capable of persisting in the environment and can be transported by bioaerosols which can further influence its transmission rate and seasonality. The COVID-19 pandemic has changed the behavior of adults and children globally. A general trend during the pandemic has been human isolation indoors due to school lockdowns and loss of job or implementation of virtual work at home. A consequence of this behavior change would presumably be changes in indoor allergen exposures and reduction of inhaled outdoor allergens. Therefore, lockdowns during the pandemic might have improved some specific allergies, while worsening others, depending on the housing conditions.

Impact of helminthiasis on gestational anemia in low- and middle-income countries: a systematic review and meta-analysis of more than 19,000 women.

Intestinal helminthiasis are a common public health problem in developed and developing countries. It is thought that they can influence pregnancy by causing gestational anemia. The aim of this study was to determine if there is a relationship between helminth infection and gestational anemia. A structured review of scientific literature was conducted through active search in the electronic databases MEDLINE® and LILACS® until December 2021, following 2020 PRISMA statement. The studies were reviewed independently by two authors, extracting the most relevant information from each study. Cross-sectional studies, case-control and ecological studies were included, with no date or language limit. Randomized clinical trials were excluded. A total of 38 studies were included in the systematic review. The study populations of all studies belonged to low- and middle-income countries: 28 studies from Africa, 6 from Asia, 3 from Latin America and 1 from Oceania. Overall, the average prevalence of gestational anemia among the included studies was 40% (95% CI 34-46%). Hookworm was the predominant species detected in most studies (19/38; 50%), followed by Ascaris lumbricoides (15/38; 39.5%). Gestational anemia was positively associated with A. lumbricoides (OR 1.86, 95% CI 1.12-3.08) and hookworms (OR 3.09, 95% CI 1.99-4.78). Prevalence of malaria was not associated with the magnitude of the effect of hookworm on anemia risk during meta-regression (p=0.5182). The results of this review indicate that there is a statistically significant association between helminthiasis and gestational anemia. Although hookworm is the main species associated with the outcome, prevalence of malaria was not associated with the magnitude of the effect of hookworm on anemia risk. The impact of other species needs to be defined given the expected bias that arises from polyparasitism when defining comparison groups.

Structural and allergenic properties of the fatty acid binding protein from shrimp Litopenaeus vannamei.

BACKGROUND: The shrimp Litopenaeus vannamei is an important source of food allergens but its allergenic repertoire is poorly characterized. Cross-reactivity between crustacean and mites has been reported, with tropomyosin, the most relevant allergen involved. The aim of this study was to investigate the structural and immunological properties of a recombinant Fatty Acid Binding Protein (FABP) family from L. vannamei (LvFABP). METHODS: ELISA, skin prick test (SPT) and basophil activation assays were performed to determine IgE reactivity and allergenic activity of LvFABP. LC-MS/MS and Circular Dichroism experiments were done for structural analysis. B-cell epitope mapping with overlapping peptides, and cross-inhibition studies using human sera were done to identify antigenic regions and cross-reactivity. RESULTS: The recombinant LvFABP bound serum IgE from 27% of 36 shrimp allergic patients and showed allergenic activity when tested for basophil activation and SPT in a selected number of them. CD-spectroscopy of LvFABP revealed that the protein is folded with a secondary structure composed of mainly ß-strands and a smaller fraction of α helices. This is consistent with molecular modelling results, which exhibit a typical ß barrel fold with two α-helices and ten ß-strands. Epitope mapping identified two IgE-binding antigenic regions and inhibition assays found high cross-reactivity between LvFABP and Blo t 13, mediated by the antigenic region involving amino acids 54 to 72. CONCLUSIONS: Our results show that LvFABP is a shrimp allergen that cross reacts with the house dust mite allergen Blo t 13 and has allergenic activity, which suggest that it could be clinically relevant in case of shellfish allergy. This new allergen, named Lit v 13, will also help to understand basic mechanisms of sensitization to shrimp.

Iron status in late pregnancy is inversely associated with birth weight in Colombia.

OBJECTIVE: Gestational anaemia (GA) is common in developing countries. This study assessed the relationship of late GA and negative perinatal outcomes in participants recruited in a reference maternity unit of the Caribbean region of Colombia. DESIGN: Prospective analytical birth cohort study. Maternal Hb and serum ferritin (SF) levels were measured. GA was defined as Hb levels <6·82 mmol/l (<11 g/dl), SF depletion as SF levels <12 µg/l. Birth outcomes such as low birth weight (LBW), preterm birth (PB) and small for gestational age (SGA) were examined. SETTING: Mothers in the first stage of labour, living in urban or rural areas of Bolívar, were enrolled in an obstetrical centre located in Cartagena, Colombia. Blood and stool samples were taken prior delivery. Maternal blood count, SF levels and infant anthropometric data were recorded for analysis. PARTICIPANTS: 1218 pregnant women aged 18-42 years and their newborns. RESULTS: Prevalence of GA and SF depletion was 41·6 % and 41·1 %, respectively. GA was positively associated with poverty-related sociodemographic conditions. Prenatal care attendance lowered the risk of PB, LBW and SGA. Birth weight was inversely associated with Hb levels, observing a -36·8 g decrease in newborn weight per 0·62 mmol/l (or 1 g/dl) of maternal Hb. SF depletion, but not anaemia, was associated with PB. SGA outcome showed a significant association with anaemia, but not a significant relationship with SF depletion. CONCLUSIONS: Birth weight and other-related perinatal outcomes are negatively associated with Hb and SF depletion. Prenatal care attendance reduced the risk of negative birth outcomes.

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

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.

Allergological Importance of Invertebrate Glutathione Transferases in Tropical Environments.

Glutathione-S transferases (GSTs) are part of a ubiquitous family of dimeric proteins that participate in detoxification reactions. It has been demonstrated that various GSTs induce allergic reactions in humans: those originating from house dust mites (HDM), cockroaches, and helminths being the best characterized. Evaluation of their allergenic activity suggests that they have a clinical impact. GST allergens belong to different classes: mu (Blo t 8, Der p 8, Der f 8, and Tyr p 8), sigma (Bla g 5 and Asc s 13), or delta (Per a 5). Also, IgE-binding molecules belonging to the pi-class have been discovered in helminths, but they are not officially recognized as allergens. In this review, we describe some aspects of the biology of GST, analyze their allergenic activity, and explore the structural aspects and clinical impact of their cross-reactivity.

Identification and Physicochemical Characterization of a New Allergen from Ascaris lumbricoides.

To analyze the impact of Ascaris lumbricoides infection on the pathogenesis and diagnosis of allergic diseases, new allergens should be identified. We report the identification of a new Ascaris lumbricoides 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 A. lumbricoides 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 A. lumbricoides.

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

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 IL13 gene and egg worm burden that remained significant after adjustment by age [-0.20 (-0.32 to -0.09), p < 0.0001]. Moreover, we found significant associations between H4Ac levels in IL4 [0.32 (0.05-0.60), p = 0.02] and CHI3L1 [0.29 (0.08-0.51), p = 0.008] with the IgE levels to Ascaris lumbricoides. In addition, the levels of specific IgE antibodies to HDM were associated with H4Ac levels in the gene TNFSF13B encoding the B cell activating factor (BAFF) [0.51 (0.26-0.76), p < 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.

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

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 P. americana; Asp f 1, Asp f 2, Asp f 3, Asp f 4 and Asp f 6 from A. fumigatus; Mala s 8 and Mala s 13 from M. sympodialis; Alt a 1 from A. alternata; Pen c 13 from P. chrysogenum; 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.

Personalized medicine for asthma in tropical regions.

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.

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

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 Ascaris lumbricoides recombinant cysteine protease inhibitor (rAl-CPI) in a mouse model of allergic airway inflammation induced by the house dust mite (HDM) Blomia tropicalis and its effects on human monocyte-derived dendritic cells (HmoDCs). The B. tropicalis sensitized/challenged mice developed extensive cellular airway inflammatory response, which was significantly reduced upon treatment with rAl-CPI prior to B. tropicalis 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. In vitro, 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.