Data-driven analysis of chemicals,proteins and pathways associated with peanut allergy:from molecular networking to biological interpretation

Peanut allergy is majorly related to severe food induced allergic reactions.Several food including cow's milk,hen's eggs,soy,wheat,peanuts,tree nuts(walnuts,hazelnuts,almonds,cashews,pecans and pistachios),fish and shellfish are responsible for more than 90%of food allergies.Here,we provide promising insights using a large-scale data-driven analysis,comparing the mechanistic feature and biological relevance of different ingredients presents in peanuts,tree nuts(walnuts,almonds,cashews,pecans and pistachios)and soybean.Additionally,we have analysed the chemical compositions of peanuts in different processed form raw,boiled and dry-roasted.Using the data-driven approach we are able to generate new hypotheses to explain why nuclear receptors like the peroxisome proliferator-activated receptors(PPARs)and its isoform and their interaction with dietary lipids may have significant effect on allergic response.The results obtained from this study will direct future experimeantal and clinical studies to understand the role of dietary lipids and PPARisoforms to exert pro-inflammatory or anti-inflammatory functions on cells of the innate immunity and influence antigen presentation to the cells of the adaptive immunity.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.

Preventive effects of Bifidobacterium lactis Probio-M8 on ovalbumin-induced food allergy in mice

Food allergy is a significant public health concern globally.Certain probiotics have been found to enhance food allergy by regulating immune-microbe interactions in animal models and patients.However,the effects of Bifidobacterium lactis Probio-M8 on food allergy have not been thoroughly investigated.The present study examined the anti-allergic properties of Probio-M8,particularly in relation to immune response and gut microbiota composition.Results demonstrate that oral administration of Probio-M8 effectively mitigated the allergy symptoms triggered by ovalbumin(OVA)by ameliorating the morphological damage in the jejunum,reducing OVA-specific IgE and histamine levels in the serum,and suppressing Th2 cytokines(interleukin(IL)4 and IL-13)while increasing Th1 cytokines(interferon(IFN)γ)and regulatory T(Treg)cytokines(IL-10 and transforming growth factor(TGF)β1)in the culture supernatants of splenic cells.Furthermore,Probio-M8 effectively altered the diversity and composition of gut microbiota,particularly the relative abundances of Akkermansia_muciniphila in OVA-induced mice.Compared to the OVA group,the Probio-M8 group showed a decrease in the relative abundance of Akkermansia_muciniphila.In conclusion,Probio-M8 demonstrates the potential to alleviate food allergy by regulating the Th1/Th2 response and modulating gut microbiota,thereby offering a novel therapeutic strategy for patients with food allergy.

Olive oil ameliorate allergic response in ovalbumin-induced food allergy mouse by promoting intestinal mucosal immunity

The numerous health benefits of olive oil are widely known,however,it also provides anti-allergic properties that have not yet been fully defined.In this study,the anti-allergic activity of olive oil was evaluated by analyzing the clinical symptoms and immune-related factors in BALB/c mice that had ingested600 mg/(kg·day)olive oil for two weeks prior to the evaluation.An allergy model was subsequently constructed for analysis,the results of which showed that the olive oil reduced the scores of allergic symptoms in the mice,and up-regulated the hypothermia and the decline in the immune organ index.Moreover,fewer allergy-related cytokines and reduced intestinal inflammation was discovered in the olive oil-treated group.In addition,analysis of intestinal mucosal immune-related factors revealed that the olive oil promoted the expression of intestinal tight junction proteins(Claudin-1,Occludin,and ZO-1)and IL-22,and helped maintain the integrity of the intestinal epithelial physical barrier.Increased levels of mucin 2 andβ-defensin were also found in the intestinal mucus of the olive oil-treated mice.These findings suggest that the oral administration of olive oil effectively attenuated the ovalbumin-induced allergic immune response in the mice,and had a positive effect on intestinal epithelial mucosal immunity.

The role of gut microbiota and its metabolites short-chain fatty acids in food allergy

Emerging evidence indicated that the increase in food allergy(FA)over the past few decades was associated with the abnormal compositional and metabolic changes of gut microbiota.Gut microbiota played a vital role in maintaining the homeostasis of the immune system and the dysbiosis of gut microbiota promoted the occurrence of FA.Recent research suggested that short-chain fatty acids(SCFAs),the main metabolites derived from gut microbiota,contributed to FA protection.Herein,we provided a comprehensive review on the relationship between gut microbiota and FA.The multifaceted mechanisms underlymg beneficial effects of gut microbiota composition/metabolites on the regulation of diverse cellular pathways in intestinal epithelial cells,dendritic cells,innate lymphoid cells,T cells,B cells and mast cells in the immune system were discussed systematically.These findings emphasized the positive function of gut microbiota in FA and provided novel ideas for the treatment or prevention of FA in the future.

The role of probiotics in prevention and treatment of food allergy

With the prevalence of food allergy increasing every year,food allergy has become a common public health problem.More and more studies have shown that probiotics can intervene in food allergy based on the intestinal mucosal immune system.Probiotics and their metabolites can interact with immune cells and gut microbiota to alleviate food allergy.This review outlines the relationship between the intestinal mucosal immune system and food allergy.This review also presents the clinical application and potential immunomodulation mechanisms of probiotics on food allergy.We aim at providing a reference for further studies to explore the key active substances and immunomodulation mechanisms of anti-allergic probiotics.

Maternal obesity exacerbates the responsiveness of offspring BALB/c mice to cow's milk protein-induced food allergy

Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.

Ultrasound-guided carotid angioplasty and stenting in a patient with iodinated contrast allergy:A case report

BACKGROUND Ischemic stroke is an entity with high incidence,morbidity,and mortality rates.Carotid artery stenosis is an important and independent risk factor for ischemic stroke.The three current approaches for treating carotid artery stenosis are drug treatment,carotid endarterectomy(CEA),carotid angioplasty and stenting(CAS).The approach is chosen based on the degree of stenosis.CEA or CAS could have been chosen for the current patient,who had severe carotid stenosis and an iodinated contrast allergy.After thoroughly communicating with the patient,the patient chose CAS for treatment.Therefore,we performed ultrasound-guided CAS to avoid the use of iodinated contrast.CASE SUMMARY The main symptoms of the patient were numbness and weakness of the left limb.Computed tomography angiography of the head and neck at another hospital indicated multiple sites of stenosis in the arteries of the head and neck.The patient requested CAS for treatment but was allergic to iodinated contrast media.Thus,routine digital subtraction angiography(DSA)with iodinated contrast could not be used for the procedure.The diagnosis of this patient was as follows:(1)Right parietal lobe cerebral infarction;(2)multiple sites of stenosis in the arteries of the head and neck(severe stenosis of the right internal carotid artery,severe stenosis of the right subclavian artery);(3)right subclavian steal syndrome;and(4)hypertension(stage 3,high risk).The interventions included routine treatment for cerebral infarction,oral administration of clopidogrel(75 mg qd)and aspirin(100 mg qd),ultrasound-guided CAS,and postoperative follow-up.Postoperative color Doppler ultrasound and cerebrovascular magnetic resonance angiography of the carotid artery showed good vascular recovery,and the postoperative follow-up indicated a good prognosis.CONCLUSION This case study suggests that ultrasound-guided endovascular treatment is a potential option for patients with contraindications to the iodinated contrast agents used in DSA-guided surgery,although excellent surgical operating skills are needed.

Very early onset perinatal constipation:Can it be cow’s milk protein allergy?

Delayed passage of meconium or constipation during the perinatal period is traditionally regarded as a signal to initiate further work up to evaluate for serious diagnoses such as Hirschsprung’s disease(HD),meconium ileus due to Cystic Fibrosis,etc.The diagnosis of HD particularly warrants invasive testing to confirm the diagnosis,such as anorectal manometry or rectal suction biopsy.What if there was another etiology of perinatal constipation,that is far lesser known?Cow’s milk protein allergy(CMPA)is often diagnosed in infants within the first few weeks of life,however,there are studies that show that the CMPA allergen can be passed from mother to an infant in-utero,therefore allowing symptoms to show as early as day one of life.The presentation is more atypical,with perinatal constipation rather than with bloody stools,diarrhea,and vomiting.The diagnosis and management would be avoidance of cow's milk protein within the diet,with results and symptom improvement in patients immediately.Therefore,we discuss whether an alternative pathway to address perinatal constipation should be further discussed and implemented to potentially avoid invasive techniques in patients.This entails first ruling out CMPA with safe,noninvasive techniques with diet modification,and if unsuccessful,then moving forward with further diagnostic modalities.

Assessment of immune responses and intestinal flora in BALB/c mice model of wheat food allergy via different sensitization methods

Increasing incidences showed that food allergies have attracted more and more attention from researchers.BALB/c mice were sensitized with wheat gluten combined with aluminum hydroxide adjuvant via intraperitoneal injection,transdermal sensitization,and oral gavage sensitization route.Results showed that all the three sensitization methods could induce allergic symptoms;increase the serum antibody(total immunoglobulin E(IgE),specific IgE,IgG,IgA)and histamine content;promote the secretion of Th2 cytokines(interleukin(IL)-4,IL-5,IL-13)and inflammatory factors(IL-6,IL-17 A,IL-10);and inhibit the production of Th1 cytokines(IFN-γ,IL-2).However,the allergic symptoms of mice sensitized by intraperitoneal injection were the most obvious among the three models.The level of serum antibodies in intraperitoneal injection group was significantly higher than control.Subsequently,16 S rRNA sequencing technology was used to analyze the intestinal flora of mice.The results showed that the abundance of Firmicutes in the wheat protein sensitized group was lower than that in the normal group,while the abundance of Bacteroidetes was higher,and Lactobacillus was the difference marker in normal group.Bacterial species diversity analysis showed that the species richness and diversity of intestinal flora in mice were decreased,the difference between mice induced by intraperitoneal injection and normal control group mice was the most significant.Taken together,these results show that among three sensitization methods used to build a mouse model with aluminum hydroxide as adjuvant,intraperitoneal injection is the comparably best way to build a mouse sensitization mode.

Seabuckthorn juice alleviates allergic symptoms in shrimp-induced food allergy mice

Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allergic symptoms,spleen index,intestinal section and diarrhea were measured in shrimp allergy mice.As the results,seabuckthorn juice suppressed the lesions in jejunum tissue,diarrhea and allergic symptoms in shrimp allergy mice.Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-a(TNF-α)as well as immunoglobulin E(IgE)and stimulated the secretion of interleukin-10(IL-10)in mice with shrimp allergy.Taken together,our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms.Furthermore,seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions,inhibiting levels of TNF-αand IgE.

Pharmacodynamics of frigid zone plant Taxus cuspidata S.et Z.against skin melanin deposition,oxidation,inflammation and allergy

Background:Taxus cuspidata S.et Z.is a precious species of frigid zone plant belonging to the Taxaceae family,which possesses anticancer,anti-inflammatory,hypoglycemic,and antibacterial pharmacological properties.While taxane extracted from Taxus chinensis has been reported to elicit antioxidant activities,whether Taxus cuspidata S.et Z.has skin-protective actions against injuries remained unknown.This study aims to explore the pharmacological effects of three Taxus extracts on skin melanin deposition,oxidation,inflammation,and allergy so as to provide new ideas for the prevention and treatment of various diseases related to skin damage.Methods:Skin melanin deposition was evaluated by measuring melanin content in the skin of guinea pigs by alkali lysis method.Antioxidant capacity was evaluated by measuring superoxide dismutase(SOD)concentration and glutathione(GSH)content in skin tissue homogenates of Kunming mice by SOD assay kit and micro reduced GSH assay kit.The quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were used to examine the levels of both SOD and recombinant glutathione peroxidase 4(GPX4).Skin inflammation was evaluated by xylene-induced ear swelling test and egg-white-induced paw swelling test in mice.In a mouse model of skin allergy induced by 4-aminopyridine(4-AP),allergy was determined by licking body counts and histamine concentrations in tissue homogenates using enzyme-linked immunosorbent assay(ELISA)kits.Two proinflammatory factors tumor necrosis factor(TNF)-αand interleukin(IL)-1βwere measured by qRT-PCR.Hematoxylin and eosin(HE)staining was conducted to assess the degree of skin lesion.Results:All three Taxus extracts including Taxus chinensis essential oil,Taxus chinensis extract and Taxus chinensis extract compound reduced the melanin deposits in the back skin relative to the non-treated control animals,of which Taxus chinensis essential oil produced the greatest effect.In contrast,the three Taxus extracts elevated SOD and GSH levels in the skin tissues,and the highest increase was seen with Taxus chinensis essential oil.Three Taxus extracts,especially Taxus chinensis essential oil,effectively reduce the rate of ear and paw swelling.All three Taxus extracts reduced the number of body licks,the levels of TNF-αand IL-1β,and the histamine content in tissue homogenates of mice and alleviated skin damage.Consistently,Taxus chinensis essential oil yielded the greatest magnitude of decreases.Conclusion:While all three Taxus extracts possessed the anti-skin melanin deposition,oxidation,and allergy properties,Taxus chinensis essential oil produced the superior effects.

Allergy identification for neurosurgical patients:updates for management

Allergic reactions in neurosurgical procedures are uncommon,but they are detrimental to a patient’s prognosis and recovery.By synthesizing data collected from other surgical fields,possible triggers and alternatives have been identified.Current treatment guidelines involve stabilizing the patient in emergency situations,symptom management,and identification of causative allergens.Preoperative allergy screening is uncommon due to the low prevalence of perioperative hypersensitivity reactions.However,preoperative questionnaire screening can identify when preoperative allergy screening,premedication,or use of a material alternative is necessary.Greater emphasis on material alternatives,increased preoperative screening,and more data can improve the prognosis of neurosurgical patients at risk of perioperative allergic complications.

Allergy Screen和EUROLINE Atopy血清过敏原特异性IgE检测结果对比分析

目的对Allergy Screen与EUROLINE Atopy过敏原特异性免疫球蛋白E(specific immunoglobulin E,sIgE)检测结果进行一致性和等级相关性研究,为临床合理应用检测方法和解读检验结果提供依据。方法收集过敏性疾病患儿血清样本180份,其中男86例,女94例,年龄3~15岁。分别应用Allergy Screen法和EUROLINE Atopy法检测血清样本中树花粉、混合草、尘螨、猫毛、狗毛、屋尘、蟑螂、霉菌、牛奶、鸡蛋、牛肉、贝类、虾、蟹过敏原sIgE。结果两种检测方法Kappa分析得出:尘螨、牛奶、蟹三项一致性最高(Kappa值分别为0.846、0.845、0.813)。混合草、屋尘、蟑螂、霉菌、鸡蛋、虾等六种过敏原一致性较高(Kappa值分别为0.719、0.722、0.662、0.652、0.780、0.710)。树花粉、牛肉一致性中等(Kappa值分别为0.483、0.486)。猫毛、贝类一致性一般(Kappa值分别为0.392、0.389)。狗毛一致性较差(Kappa值为0.142)。两种检测方法过敏原sIgE的等级资料Spearman相关性分析显示:混合草、尘螨、屋尘、牛奶、鸡蛋、虾、蟹等7项相关性非常紧密(Spearman值分别为0.735、0.878、0.707、0.835、0.821、0.704、0.826),蟑螂、霉菌组合、牛肉等3项相关性紧密(Spearman值分别为0.670、0.689、0.445)。树花粉、猫毛、狗毛、贝类等4项相关性一般(Spearman值分别为0.389、0.324、0.237、0.311)。结论两种检测方法大部分项目过敏原sIgE不仅具有较强一致性,还具有非常紧密的等级相关性,二者均可用于一般过敏性疾病的筛查,临床医生和实验室应该综合分析,合理科学地选择检测方法。

采用Allergy Lateral Flow Assay检测过敏原特异性IgE抗体的性能评价

目的Allergy Lateral Flow Assay(ALFA)是一种便捷、小巧的过敏原检测新技术,本研究以荧光酶联免疫全定量ImmunoCAP法为“金标准”,旨在探讨ALFA的检验效能及在中国南方地区的应用价值。方法利用ALFA技术与ImmunoCAP技术检测100例过敏性疾病患者血清屋尘螨、粉尘螨、热带无爪螨、猫毛皮屑、狗毛皮屑、蟑螂和艾蒿sIgE水平。结果以ImmunoCAP法为“金标准”,结果显示,ALFA检测粉尘螨的一致性最高(κ=0.56,P<0.05),其次是屋尘螨(κ=0.43,P<0.05);同时,ALFA检测粉尘螨(87.6%)、猫毛皮屑(73.7%)和屋尘螨(87.6%)的总一致率均较高。经受试者工作特征曲线分析显示,ALFA诊断螨类过敏原的曲线下面积均大于0.90(P<0.05)。对于屋尘螨、粉尘螨和猫毛皮屑过敏原,ALFA与ImmunoCAP系统的sIgE检测结果具有强相关性(r I>0.8,P<0.05)。结论ALFA具有良好的诊断效能,可满足临床检测要求,因其无须昂贵的检测仪器和检测费用,可为基层医院临床筛查应用提供新的选择。

Pathophysiological Justification for Allergen Immunotherapy in Food Allergy

Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI in treating allergic rhinitis, asthma or allergy to the venom of Hymenoptera insects. It has also been proven that administration of increasing preparation doses of allergen extractions alleviates the symptoms in patients after the exposure to some sensitizing allergens. The effect of the AI remains visible many years after completion of the therapy. Studies have been done in an attempt to employ specific immunotherapy in patients with food allergy symptoms. They have been mostly concerned with populations of patients suffering from allergy to the protein found in cow’s milk and hen eggs. It appears that a need arises to create a new therapeutic method for successful treatment of food allergies and specific allergen immunotherapy seems to be a promising step. Although still in its experimental phase, in many well documented cases the method allows for building patient’s tolerance towards small doses of sensitizing allergen and seems conducive to protecting the patient from anaphylactic reactions after incidental allergen consumption.

Research Progress of Evaluation Models of Cosmetic Anti-Allergy Safety

YiwenAbstractThe aim of this study was to explore the mechanism of skin allergic reactions,and the role of skin allergic mediators in different types of allergic reactions.Further,we reviewed and classified anti-allergic safety evaluation models of cosmetics based on skin allergic media.In addition,the study explored in vitro experiments,cell experiments and animal experiments performed using anti-allergic safety evaluation model.The findings of this study provide information on the importance of anti-allergic safety evaluation models in cosmetics industry,and guides on selection of anti-allergic raw materials.Moreover,the findings of this study provide a basis for further research on development of mild cosmetics.

Allergy-related Evidences in Relation to Serum IgE:Data from the China State Key Laboratory of Respiratory Disease,2008-2013

Objective To investigate the serum total IgE （tlgE） and specific IgE （slgE） to common allergens among allergic patients in Guangzhou, China. Methods 7 085 patients were examined for tlgE and slgE to 15 allergens, based on the protocols of reversed enzyme allergosorbent test and the sandwich enzyme-linked immunosorbent assay. Results 3 758 （53.04%） patients tested positive for tlgE, and 4 640 （65.49%） for slgE. Der pteronyssinus, Derfarinae, eggs, and cow＇s milk were the most common allergens leading to higher positive rates of slgE responses. Several peaks of sensitization were： Der pteronyssinus, Derfarinae, and Blomia tropicalis at age 10-12; cow＇s milk at age below 3; eggs at age 4-6. The mean level and positive rate of tlgE tended to increase in subjects sensitized to more allergens. Sensitization to Der pteronyssinus （OR, 1.6; P〈O.05）, Der farinae （OR, 1.5; P〈O.05）, Blomia tropicalis （OR, 1.4; P〈O.05）, Blattella germanica （OR, 1.5; P〈O.05）, cow＇s milk （OR, 1.3; P〈O.05）, and soy beans （OR, 2.0; P〈O.05） were independently correlated with allergy-related conditions in preliminary diagnosis. Conclusion The major allergens in Guangzhou include Derpteronyssinus, Derfarinae, cow＇s milk, and eggs. Sensitization to these allergens appears to be predictors of allergy-related disorder.

Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity

Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.