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Keywords = component-resolved diagnostics (CRD)

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19 pages, 2277 KB  
Review
Predicting Oral Food Challenge Outcomes in Cow’s Milk Protein Allergy: The Crucial Role of Bos d 8 and Component-Resolved Diagnostics: A Narrative Review
by Weronika Balas, Aleksandra Tylewicz, Weronika Gromek, Weronika Sobota, Adam Sybilski and Emilia Majsiak
Int. J. Mol. Sci. 2026, 27(8), 3643; https://doi.org/10.3390/ijms27083643 - 19 Apr 2026
Viewed by 552
Abstract
Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds [...] Read more.
Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds for cow’s milk protein in predicting outcomes of OFCs in European children. Eligible studies focusing on CRD in European pediatric populations were identified through PubMed and Scopus databases. Our findings highlight the crucial role of Bos d 8 (casein) in the diagnostic process. Among the analyzed milk components, Bos d 8 appeared to be a promising marker for predicting positive OFC outcomes in several cohorts. However, due to significant population heterogeneity, conflicting findings exist, with some studies indicating that no single molecular component is consistently superior to whole cow’s milk specific IgE. While other molecules, such as Bos d 6 and lactoferrin, showed limited diagnostic utility, specific IgE to Bos d 8 demonstrated the highest clinical value. Although the double-blind, placebo-controlled food challenge (DBPCFC) remains the gold standard for CMPA diagnosis, the use of Bos d 8 in CRD is a key step toward risk stratification and may help reduce the need for high-risk OFCs in selected patients. Full article
(This article belongs to the Special Issue Molecular Therapeutic Strategies in Allergic Diseases)
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26 pages, 2090 KB  
Review
Wheat Allergy in the Era of Precision Medicine: From Novel Molecular Markers to New Therapeutic Perspectives
by Solomiya Pukalyak, Weronika Gromek, Aleksandra Tomczak, Ewa Markut-Miotła, Maja Woźniak, Mariusz Wysokiński, Sylwia Smolinska and Emilia Majsiak
Int. J. Mol. Sci. 2026, 27(4), 1717; https://doi.org/10.3390/ijms27041717 - 10 Feb 2026
Cited by 2 | Viewed by 1271
Abstract
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise [...] Read more.
Wheat allergy (WA) poses a diagnostic challenge due to its diverse clinical phenotypes—ranging from classic food allergy and wheat-dependent exercise-induced anaphylaxis (WDEIA) to baker’s asthma. An additional diagnostic aspect is serological cross-reactivity with grass pollen. Undoubtedly, the transition from extract-based diagnostics to precise component-based diagnostics (CRDs) facilitates the management of wheat allergy. It has significantly improved the diagnostic accuracy for WDEIA ω-5-gliadin (Tri a 19), although considering new knowledge about wheat proteins, it seems necessary to include them in the diagnostic scheme, especially where Tri a 19 remains negative despite clinical symptoms. Therefore, in this review, we evaluate the clinical utility of new wheat molecules with a high risk of anaphylaxis. We pay particular attention to Tri a 37 (α-purothionin), a thermally stable allergen associated with a 4-fold increase in the risk of severe anaphylaxis, and Tri a 36 (LMW glutenin), which shows higher sensitivity than Tri a 19 in specific pediatric cohorts. In addition, we emphasize the role of Tri a 14 (nsLTP) in distinguishing true wheat sensitization from pollen-related cross-reactivity caused by profilins (Tri a 12) or carbohydrate determinants (CCDs). Beyond diagnostics, the review discusses dynamic changes in sensitization profiles in relation to the allergic march and the phenomenon of spontaneous remission in children. New management strategies are also discussed, including the potential of omalizumab (based on the data from the OUtMATCH study) in facilitating the reintroduction of allergens into the diet. Full article
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21 pages, 335 KB  
Review
Diagnosis of Food Allergy: Which Tests Truly Have Clinical Value?
by Katarzyna Napiorkowska-Baran, Alicja Gruszka-Koselska, Karolina Osinska, Gary Andrew Margossian, Carla Liana Margossian, Aleksandra Wojtkiewicz, Pawel Treichel and Jozef Slawatycki
Allergies 2026, 6(1), 3; https://doi.org/10.3390/allergies6010003 - 27 Jan 2026
Viewed by 2928
Abstract
Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review [...] Read more.
Food allergy diagnosis remains challenging due to the difficulty of distinguishing true clinical allergy from asymptomatic sensitization. Inaccurate diagnosis may result in unnecessary dietary restrictions, reduced quality of life, or, conversely, failure to identify individuals at risk of severe allergic reactions. This review critically analyzes the efficacy, limitations, and clinical utility of currently available diagnostic tests for food allergy, with particular emphasis on their ability to predict true clinical reactivity. A comprehensive literature review was conducted to evaluate the sensitivity, specificity, and predictive values of both traditional and emerging diagnostic modalities. English-language guidelines, systematic reviews, and key clinical studies published primarily within the past 15 years (up to 2025) were identified through PubMed and Google Scholar. Classic diagnostic tools, including skin prick testing (SPT) and serum-specific IgE (sIgE), were assessed alongside novel approaches such as component-resolved diagnostics (CRD), basophil activation test (BAT), mast cell activation test (MAT), atopy patch testing (APT), cytokine profiling, and omics-based diagnostics. Particular attention was given to how these tests compare with the oral food challenge (OFC), which remains the diagnostic gold standard. The findings demonstrate that while conventional tests offer high sensitivity and are valuable for initial risk assessment, their limited specificity often leads to overdiagnosis. Emerging molecular and cellular assays show improved specificity and functional relevance, especially in complex cases involving polysensitization or unclear clinical histories and may reduce reliance on OFCs in the future. However, accessibility, cost, and lack of standardization currently limit their widespread clinical application. Advances in artificial intelligence and data integration hold promise for improving diagnostic accuracy through enhanced interpretation of complex immunological data. Based on the synthesized evidence, this review proposes an evidence-based, stepwise, and individualized diagnostic algorithm for food allergy. Integrating clinical history, targeted testing, and selective use of OFCs can improve diagnostic certainty, enhance food safety, minimize unnecessary dietary avoidance, and optimize patient outcomes. The review underscores the need for continued research, standardization, and validation of novel diagnostic tools to support personalized and precise food allergy management. Full article
(This article belongs to the Section Food Allergy)
20 pages, 1170 KB  
Review
Dietary Management of Eosinophilic Esophagitis in the Era of Molecular Diagnostics: The Role and Limitations of Component-Resolved Diagnostics—A Narrative Review
by Adam Wawrzeńczyk, Katarzyna Napiórkowska-Baran, Maciej Szota, Paweł Treichel, Justyna Durślewicz and Zbigniew Bartuzi
Nutrients 2025, 17(22), 3588; https://doi.org/10.3390/nu17223588 - 17 Nov 2025
Viewed by 2119
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder characterized by eosinophilic infiltration of the esophageal epithelium, primarily driven by exposure to food and aeroallergens. Although dietary elimination remains the cornerstone of therapy, the identification of specific food triggers still largely relies on empiric [...] Read more.
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder characterized by eosinophilic infiltration of the esophageal epithelium, primarily driven by exposure to food and aeroallergens. Although dietary elimination remains the cornerstone of therapy, the identification of specific food triggers still largely relies on empiric methods. This narrative review explores the diagnostic and therapeutic role of component-resolved diagnostics (CRD) and other molecular tools in the personalized management of EoE. Across observational and cohort studies, CRD has shown improved sensitivity in detecting clinically relevant allergen sensitizations compared with conventional tests, allowing for more precise dietary guidance and, in some cases, reducing unnecessary food exclusions. However, remission rates achieved through CRD-guided diets remain comparable or slightly lower than those obtained with empiric elimination, highlighting the need for validation in prospective, controlled studies. Recent advances in omics-based diagnostics, including gene expression profiling and proteomic biomarkers, further underscore the potential of integrating molecular and immunologic endotyping into clinical practice. Overall, current evidence supports CRD as a promising adjunctive tool that enhances the precision of allergen identification but is not yet ready to replace empiric dietary strategies. Future research should focus on validating standardized CRD-guided algorithms, integrating omics-derived biomarkers, and developing non-invasive diagnostic platforms. Incorporating dietitian-led nutritional assessment and biomarker monitoring into CRD- and omics-informed care pathways may help prevent nutrient deficiencies, improve adherence, and translate molecular precision into safer, patient-centered dietary management. Full article
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16 pages, 278 KB  
Review
Component-Resolved and Multiplex-Specific IgE Diagnostics: Utility in Anaphylaxis and Beyond
by Mirjana Turkalj, Ivana Banić and Gordana Fressl Juroš
Children 2025, 12(7), 933; https://doi.org/10.3390/children12070933 - 16 Jul 2025
Cited by 5 | Viewed by 4040
Abstract
The diagnosis of allergic diseases and anaphylaxis is complex and encompasses a broad spectrum of in vitro and in vivo diagnostic tests. The choice of diagnostic tests is related to the presumed pathophysiological mechanism of the allergic reaction. In the past decade the [...] Read more.
The diagnosis of allergic diseases and anaphylaxis is complex and encompasses a broad spectrum of in vitro and in vivo diagnostic tests. The choice of diagnostic tests is related to the presumed pathophysiological mechanism of the allergic reaction. In the past decade the implementation of component-resolved diagnostics (CRD) into clinical practice has significantly improved the depicting of sensitization profiles, which has aided in the assessment of clinically relevant allergen components that are associated with true allergy, as well as the levels of risk of severe anaphylactic reactions. Recently, multiplex-specific immunoglobulin E (IgE) platforms have emerged for better selection of patients at risk for anaphylaxis and have improved the selection criteria for patients undergoing allergen immunotherapy, including novel regimes such as oral immunotherapy. This review describes the advantages of the utilization of component-resolved diagnostics and multiplex assays in clinical settings, especially in cases of anaphylaxis when no clear trigger is recognized or where multiple culprits are suspected. As multiplex component-resolved diagnostics becomes more readily available globally and with the use of novel approaches, CRD will certainly be a crucial tool in personalized and individually tailored management plans and reduce the financial burden of anaphylaxis. Full article
15 pages, 752 KB  
Review
Tree Nut Allergy in Children—What Do We Know? —A Review
by Anna Chudoba, Agata Żebrowska and Adam J. Sybilski
Nutrients 2024, 16(23), 3978; https://doi.org/10.3390/nu16233978 - 21 Nov 2024
Cited by 8 | Viewed by 6118
Abstract
Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of [...] Read more.
Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of tree nut allergy are limited. Primary nut allergy typically presents with rapid-onset IgE-mediated symptoms. Diagnosis can be confirmed by demonstrating a positive skin prick test (SPT), specific IgE (sIgE), or through an oral food challenge. Component-resolved diagnostics (CRD) can identify those with a high risk of anaphylaxis. The main management strategy involves avoiding the culprit allergen and treating symptoms after accidental exposure. New therapeutic options, such as sublingual immunotherapy, oral food immunotherapy, with or without omalizumab, and other monoclonal antibodies, are being investigated to modify tree nut allergy. Tree nut allergy is a lifelong disease with a low likelihood of resolution. The aim of this paper is to present the current data on the prevalence, diagnosis, natural history, and management options for tree nut allergy. Full article
(This article belongs to the Section Pediatric Nutrition)
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16 pages, 5840 KB  
Article
Combined Integrative RNA-Seq and Serological sIgE Analysis Enhances Understanding of Fish Allergen Profiles and Diagnostic Strategy for Fish Allergy
by Zhong-Yi Liu, Christine Yee Yan Wai, Agnes Sze Yin Leung, Wai Hung Chan, Jaime Sou Rosa Duque, Ivan Cheuk San Lam, James Wesley Cheng, Jason Ka Chun Sit, Noelle Anne Ngai, Po Ki Ho, Gilbert T. Chua, Qun Ui Lee, Oi Man Chan, Yat Sun Yau, Joshua Sung Chi Wong, David Chi Kong Luk, Marco Hok Kung Ho, Mike Yat Wah Kwan, Man Fung Tang, Nicki Yat Hin Leung and Ting Fan Leungadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2024, 25(19), 10784; https://doi.org/10.3390/ijms251910784 - 7 Oct 2024
Cited by 6 | Viewed by 2780
Abstract
Fish allergy is a significant health concern, with diagnosis and management complicated by diverse fish species and allergens. We conducted a comprehensive RNA-seq analysis of eight fish species to identify allergen profiles, integrating ImmunoCAP sIgE data to explore associations with allergen expression and [...] Read more.
Fish allergy is a significant health concern, with diagnosis and management complicated by diverse fish species and allergens. We conducted a comprehensive RNA-seq analysis of eight fish species to identify allergen profiles, integrating ImmunoCAP sIgE data to explore associations with allergen expression and diagnostic performance. Over 30 putative fish allergens were identified, with varying sequence similarities and expression levels, roughly classifying fish into two groups based on parvalbumin (PV) expression. Higher similarities in allergen expression correlated with stronger sIgE data relationships among fish extracts. High PV expression and conserved PV sequences were linked to elevated sIgE measurements, potentially indicating higher allergenicity. For diagnosis, species-specific extract sIgE remained the best indicator of corresponding fish allergy diagnosis, while incorporating multiple sIgE data enhanced performance. In component-resolved diagnosis (CRD), the current panel with PV alone showed comparable performance to fish extract for PV-high fish allergy, while PV-low fish may require the inclusion of more minor allergens for improved CRD accuracy. This RNA-seq allergen analysis helps reveal fish allergen profiles, classify fish groups, and predict allergenicity, potentially improving CRD design and food management in fish allergy. Full article
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15 pages, 1934 KB  
Article
Amino Acid Profiling Identifies Disease-Specific Signatures in IgE-Mediated and Non-IgE-Mediated Food Allergy in Pediatric Patients with Atopic Dermatitis
by Kacper Packi, Joanna Matysiak, Szymon Plewa, Agnieszka Klupczyńska-Gabryszak, Eliza Matuszewska, Natalia Rzetecka, Anna Bręborowicz and Jan Matysiak
Biomedicines 2023, 11(7), 1919; https://doi.org/10.3390/biomedicines11071919 - 6 Jul 2023
Cited by 2 | Viewed by 2957
Abstract
An IgE-mediated food allergy (FA) in atopic dermatitis (AD) children should be easily differentiated from other immune-mediated adverse effects related to food. Specific IgEs for particular protein components has provided additional diagnostic value. However, component-resolved diagnostics (CRD) has not solved all diagnostic problems [...] Read more.
An IgE-mediated food allergy (FA) in atopic dermatitis (AD) children should be easily differentiated from other immune-mediated adverse effects related to food. Specific IgEs for particular protein components has provided additional diagnostic value. However, component-resolved diagnostics (CRD) has not solved all diagnostic problems either. We analysed the serum profile of 42 amino acids (AAs) in 76 AD children aged 2–60 months with an IgE-mediated FA (n = 36), with a non-IgE-mediated FA (n = 15) and without an FA (n = 25) using high-performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) and an aTRAQ kit. We identified homocitrulline (Hcit), sarcosine (Sar) and L-tyrosine (Tyr) as features that differentiated the studied groups (one-way ANOVA with least significant difference post hoc test). The Hcit concentrations in the non-IgE-mediated FA group were significantly decreased compared with the IgE-mediated FA group (p = 0.018) and the control group (p = 0.008). In AD children with a non-IgE-mediated FA, the Tyr levels were also significantly reduced compared with the controls (p = 0.009). The mean concentration of Sar was the highest in the non-IgE-mediated FA group and the lowest in the IgE-mediated FA group (p = 0.047). Future studies should elucidate the involvement of these AAs in the molecular pathway of IgE- and non-IgE-mediated allergic responses. Full article
(This article belongs to the Special Issue Disease Biomarkers in Immunomediated Diseases)
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10 pages, 960 KB  
Article
House Dust Mite Precision Allergy Molecular Diagnosis (PAMD@) in the Th2-prone Atopic Dermatitis Endotype
by Ruperto González-Pérez, Paloma Poza-Guedes, Fernando Pineda, Miriam Castillo and Inmaculada Sánchez-Machín
Life 2021, 11(12), 1418; https://doi.org/10.3390/life11121418 - 17 Dec 2021
Cited by 16 | Viewed by 4947
Abstract
Atopic dermatitis (AD) endotyping might be important for developing personalized diagnostic and therapeutic strategies to the different phenotypes. The current study investigated the IgE molecular profile to Dermatophagoides pteronyssinus (D. pteronyssinus) in a subset of patients afflicted with varying severity stages [...] Read more.
Atopic dermatitis (AD) endotyping might be important for developing personalized diagnostic and therapeutic strategies to the different phenotypes. The current study investigated the IgE molecular profile to Dermatophagoides pteronyssinus (D. pteronyssinus) in a subset of patients afflicted with varying severity stages of atopic dermatitis in a subtropical region subjected to a high perennial house dust mite (HDM) exposure. We selected patients showing a clinically relevant sensitization to HDM with mild-to-moderate and severe AD according to their basal Severity Scoring Atopic Dermatitis (SCORAD) index. Skin prick test (SPT) with standardized mite extracts, as well as a Precision Allergy Molecular Diagnosis (PAMD@) panel including nine different D. pteronyssinus allergens and the related protein allergenic characterization, were assessed in all serum samples. A total of 80 European American AD patients with the marked T2 endotype confirmed their eligibility for the study. Major allergens (Der p 23, Der p 2, and Der p 1) were present in more than 86% of all subjects, with mid-tier allergens (Der p 5, Der p 7, and Der p 21) reaching up to 65%. A serodominant role for Der p 11 could not be quantitatively confirmed in the present cohort. The proposed component resolved diagnosis (CRD) panel appeared to be sufficient to obtain a precise D. pteronyssinus molecular diagnosis in AD patients subjected to a climate-dependent high-mite allergen exposure. The raised seroprevalence of IgE response to Der p 23 confirmed this constituent as a major D. pteronyssinus allergen in severe stages of atopic dermatitis. A clinically driven molecular approach appears to be essential to frame a more precise diagnosis and therapy of this heterogeneous allergic condition. Full article
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15 pages, 848 KB  
Review
Food Allergy a Constant Concern to the Medical World and Healthcare Providers: Practical Aspects
by Lucia M. Sur, Ionel Armat, Emanuela Duca, Genel Sur, Iulia Lupan, Daniel Sur, Gabriel Samasca, Cecilia Lazea and Calin Lazar
Life 2021, 11(11), 1204; https://doi.org/10.3390/life11111204 - 8 Nov 2021
Cited by 5 | Viewed by 3297
Abstract
Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis [...] Read more.
Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies. Full article
(This article belongs to the Section Medical Research)
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20 pages, 417 KB  
Review
Component-Resolved Diagnosis in Food Allergies
by Elisabetta Calamelli, Lucia Liotti, Isadora Beghetti, Valentina Piccinno, Laura Serra and Paolo Bottau
Medicina 2019, 55(8), 498; https://doi.org/10.3390/medicina55080498 - 18 Aug 2019
Cited by 58 | Viewed by 8659
Abstract
Component-resolved diagnostics (CRD) in food allergies is an approach utilized to characterize the molecular components of each allergen involved in a specific IgE (sIgE)-mediated response. In the clinical practice, CRD can improve diagnostic accuracy and assist the physician in many aspects of the [...] Read more.
Component-resolved diagnostics (CRD) in food allergies is an approach utilized to characterize the molecular components of each allergen involved in a specific IgE (sIgE)-mediated response. In the clinical practice, CRD can improve diagnostic accuracy and assist the physician in many aspects of the allergy work-up. CRD allows for discriminatory co-sensitization versus cross-sensitization phenomena and can be useful to stratify the clinical risk associated with a specific sensitization pattern, in addition to the oral food challenge (OFC). Despite this, there are still some unmet needs, such as the risk of over-prescribing unnecessary elimination diets and adrenaline auto-injectors. Moreover, up until now, none of the identified sIgE cutoff have shown a specificity and sensitivity profile as accurate as the OFC, which is the gold standard in diagnosing food allergies. In light of this, the aim of this review is to summarize the most relevant concepts in the field of CRD in food allergy and to provide a practical approach useful in clinical practice. Full article
(This article belongs to the Special Issue Food Allergies)
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