Quan, P.L. (Paola Leonor)
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- Axillary lymph node imaging in mRNA, vector-based, and mix-and-match COVID-19 vaccine recipients: ultrasound features(Springer, 2022) Soriano, I. (Ignacio); Igual-Rouilleault, A.C. (Alba Cristina); Elizalde, A. (Arlette); Quan, P.L. (Paola Leonor); Fernandez-Montero, A. (Alejandro); Pina, L. (Luis); Sobrido, C. (Carolina)Objectives To assess ultrasound characteristics of ipsilateral axillary lymph nodes after two doses of four different COVID-19 vaccination protocols, to determine whether these parameters differed with age, and to describe how they changed on follow-up imaging. Methods A total of 247 volunteer employees from our center who had received two doses of COVID-19 vaccination were recruited and followed prospectively. Axillary ultrasound of the ipsilateral vaccinated arm was performed the week after receiving the second dose to analyze lymph node features (number, long-axis, cortical thickness, morphology, and vascular imaging). Axillary lymphadenopathy resulting from four vaccination protocols—mRNA (BNT162b2, mRNA-1273), ChAdOx1-S, and mix-and-match—was compared. Analysis was conducted using the Kruskal-Wallis test and post hoc analysis with Bonferroni corrections. Nodal reactogenicity was evaluated for two age groups: young (< 45 years old) and middle-aged ( ≥ 45 years old). All parameters were compared between both groups using an unpaired-sample Student t test. A p value < 0.05 was considered statistically significant. Results Significantly higher values for total number of visible nodes, cortical thickness, Bedi’s classification (p < 0.001), and vascularity (p < 0.05) were observed in mRNA vaccine recipients compared to full ChAdOx1-S protocol recipients. Moreover, mix-and-match protocol recipients showed greater nodal cortical thickness and higher Bedi’s classification than full ChAdOx1-S recipients (p < 0.001). Analyses between age groups revealed greater cortical thickness, Bedi’s classification, and color Doppler signal in younger patients (p < 0.05). Conclusions Nodal parameters of Bedi’s classification and cortical thickness were more often increased in mRNA and mix-andmatch vaccine recipients when compared to ChAdOx1-S vaccine alone, especially in younger patients. Key Points • Hyperplastic lymphadenopathy was observed more frequently in mRNA and mix-and-match vaccine protocols compared to full vector-based vaccination. • Higher values for cortical thickness, Bedi’s classification, and color Doppler signal parameters were identified in younger patients. • Observed lymph node findings normalized in greater than 80% of patients by the third month following vaccination.
- Optimising the utility of in vitro tests for the diagnosis of drug allergy: insights from a clinical perspective(Springer, 2023) Sabaté-Brescó, M. (Marina); Goikoetxea-Lapresa, M.J. (María José); Quan, P.L. (Paola Leonor)Purpose of review To outline currently validated in vitro tests for the diagnosis of drug hypersensivity reactions (DHRs) and to provide useful strategies to optimise the utility of these tools. Recent findings Regarding in vitro tests for DHR, the main concern, at present, is low sensitivity. Thus, most of the efforts are currently directed towards improving the existing techniques and developing new assays with better diagnostic performance. Summary The management of DHRs is particularly challenging. Current strategies for diagnosis are focused on taking a thorough clinical history, evaluating sensitization using skin testing and performing supervised challenges. In vitro tests may potentially add information to the diagnostic algorithms for the management of DHRs. The presently available assays, however, pose significant limitations in terms of availability and validation. Maximizing their yield and accuracy, therefore, requires a tailored approach, focused on an appropriate clinical characterisation of the reaction. The time elapsed between drug administration and symptom presentation, as well as symptom duration, should be closely taken into consideration. In this review, existing validated in vitro techniques that may support the diagnosis of both immediate and non-immediate DHRs are summarised. Clues for optimizing their diagnostic yield are given.
- The multifaceted Mas-related G Protein-coupled receptor member X2 in allergic diseases and beyond(MDPI, 2021) Sabaté-Brescó, M. (Marina); Gastaminza, G. (Gabriel); Quan, P.L. (Paola Leonor); Guo, Y. (Yanro); Martín, M. (Margarita)Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.
- Unilateral axillary adenopathy induced by COVID-19 vaccine: US follow-up evaluation(Springer, 2022) Soriano, I. (Ignacio); Igual-Rouilleault, A.C. (Alba Cristina); Elizalde, A. (Arlette); Quan, P.L. (Paola Leonor); Fernandez-Montero, A. (Alejandro); Pina, L. (Luis)Objectives This study was conducted in order to investigate COVID-19 vaccine influence on unilateral axillary lymph nodes, comparing nodal basal features with their characteristics after the first and second vaccination dose. Methods Ninety-one volunteer employees from our center who participated in the BNT162b2 (Pfizer-BioNTech) vaccination campaign were prospectively recruited. A total of three axillary ultrasound evaluations of the ipsilateral vaccinated arm were performed: before vaccination, the week after the first dose and the week after the second dose. The following findings were recorded: the total number of visible nodes, the maximum measurements of the diameter and cortex, Bedi’s classification, and color Doppler evaluation. The collected data were compared using paired-sample Student’s t-test for quantitative continuous variables and Wilcoxon rank-sum test for ordinal variables. Additional analyses were performed after classifying patients according to the previous history of COVID-19 disease. Differences among both groups were evaluated with the Mann–Whitney U test. Variables with a p value < 0.05 were considered statistically significant. Results Comparative analyses between the three US examinations showed a statistically significant augmentation of total visible nodes, maximum diameter, cortical thickness, grade of Bedi’s classification, and Doppler signal (p < 0.001). Analyses between patients with and without previous COVID-19 infection showed a higher lymph node response in naïve patients compared to those who were previously infected. Conclusions According to our results, both doses of COVID-19 vaccine induced an increase of all axillary lymph node parameters with statistically significant differences, especially in coronavirus-naïve patients.
- Prediction of effective humoral response to SARS‑CoV‑2 vaccines in healthy subjects by cortical thickness of post‑vaccination reactive lymphadenopathy(2023) Soriano, I. (Ignacio); Pozo, J.L. (José Luis) del; Igual-Rouilleault, A.C. (Alba Cristina); Gonzalez-Hernandez, A. (Alvaro); Elizalde, A. (Arlette); Quan, P.L. (Paola Leonor); Fernández-Ciriza, L. (Leire); Fernandez-Montero, A. (Alejandro); Reina, G. (Gabriel); Pina, L. (Luis)Purpose To study the association between ultrasound cortical thickness in reactive post-vaccination lymph nodes and the elicited humoral response and to evaluate the performance of cortical thickness as a predictor of vaccine effectiveness in patients with and without a previous history of COVID-19 infection. Methods A total of 156 healthy volunteers were recruited and followed prospectively after receiving two COVID-19 vaccination doses using different protocols. Within a week after receiving the second dose, an axillary ultrasound of the ipsilateral vaccinated arm was performed, and serial post-vaccination serologic tests (PVST) were collected. Maximum cortical thickness was chosen as a nodal feature to analyze association with humoral immunity. Total antibodies quantified during consecutive PVST in previously-infected patients and in coronavirus-naïve volunteers were compared (Mann–Whitney U test). The association between hyperplastic-reactive lymph nodes and effective humoral response was studied (odds ratio). The performance of cortical thickness in detecting vaccination effectiveness was evaluated (area under the ROC curve). Results Significantly higher values for total antibodies were observed in volunteers with a previous history of COVID-19 infection (p < 0.001). The odds ratio associating immunized coronavirus-naïve volunteers after 90 and 180 days of the second dose with a cortical thickness ≥ 3 mm was statistically significant (95% CI 1.52–6.97 and 95% CI 1.47–7.29, respectively). The best AUC result was obtained comparing antibody secretion of coronavirus-naïve volunteers at 180 days (0.738). Conclusions Ultrasound cortical thickness of reactive lymph nodes in coronavirus-naïve patients may reflect antibody production and a long-term effective humoral response elicited by vaccination. Clinical relevance statement In coronavirus-naïve patients, ultrasound cortical thickness of post-vaccination reactive lymphadenopathy shows a positive association with protective antibody titers against SARS-CoV-2, especially in the long term, providing new insights into previous publications.
- Validation of a commercial allergen microarray platform for specific immunoglobulin E detection of respiratory and plant food allergens(2022) Sabaté-Brescó, M. (Marina); Goikoetxea-Lapresa, M.J. (María José); Gastaminza, G. (Gabriel); Moya, C. (Carmen); Blanca-López, N. (Natalia); Alvarado, M.I. (María Isabel); Quan, P.L. (Paola Leonor); Bartra, J. (Joan); D'Amelio-Garofalo, C.M. (Carmen Mariana); Garcia, B.E. (Blanca Esther); Fernandez, J. (Javier); Ferrer-Cardona, M. (Marta); Pascal, M. (Mariona)Background As the use of multiplex-specific immunoglobulin E (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. Objective To evaluate the clinical and technical performance of a newly introduced microarray platform, Allergy Explorer (ALEX) (MacroArray Diagnostics), in the diagnosis of pollen (cypress, grass, olive), dust mite (Dermatophagoides pteronyssinus), mold (Alternaria alternata), fruit (apple, peach), and nut (walnut, hazelnut and peanut) allergies and to compare it with those of the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) 112 microarray and the ImmunoCAP singleplex method (ThermoFisher Scientific). Methods We enrolled 153 patients with allergy and 16 controls without atopy. The sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and interassay, interbatch, and interlaboratory reproducibility. Results When measured globally (detection by 1 or more allergen components), ALEX2 had adequate sensitivity and specificity for most of the allergens studied, comparable in general with that of ISAC112 (except for olive pollen and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis revealed comparable results for all techniques, except for Ole e 1 and Jug r 3, in both ISAC112 and ImmunoCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. Conclusion ALEX2 has sound technical performance and adequate diagnostic capacity, comparable in general with that of ISAC112 and ImmunoCAP.
- Reliability of a novel electro-medical device for wheal size measurement in allergy skin testing: An exploratory clinical trial(Wiley, 2023) Tejero, E. (Eduardo); Sánchez-Fernández, S. (Sergio); Goikoetxea-Lapresa, M.J. (María José); Gastaminza, G. (Gabriel); Urtasun, M. (Maite); Giménez, R. (Rosa); Matellanes, O. (Óscar); Larrea, C. (Carla); Iñiguez, M.T. (María Teresa); Quan, P.L. (Paola Leonor); Carvallo, Á. (Álvaro); D'Amelio-Garofalo, C.M. (Carmen Mariana); Morales-Palacios, M. P. (María de la Paz); Ferrer-Cardona, M. (Marta); Nuñez-Cordoba, J.M. (Jorge M.)Skin prick testing (SPT) is the cornerstone of IgE-mediated allergy diagnosis,1 due to its high sensitivity and specificity.2 However, a uniform method for wheal measurement does not exist. Ansotegui et al.2 recommends to measure wheals in millimeters with a ruler, in many centers they are outlined with a pen and transfer by tape to a paper and then measured. Subsequently, the specialist is able to manually measure the maximum (MD) and orthogonal diameter (OD) of the wheal. This procedure is time consuming and makes repro-ducible measurements difficult.2,3 Knowing the wheal's area could help make a more accurate diagnosis.4 Over the last 30 years, many attempts have been made to develop a device to measure the size of SPT.3 Nexkin DSPT® (Figure S1A,B) is a novel mechatronic system based on 3D laser technology, that automatically locates allergen's wheal and measures its size (MD, OD and area in square millimeters) (Figure S1C).
- Validation of a commercial allergen microarray platform for specific immunoglobulin E detection of respiratory and plant food allergens - Improvement of the Elevated Tryptase Criterion to Discriminate IgE- From Non–IgE-Mediated Allergic Reactions - Validation of novel recipes for masking peanuts in double-blind, placebo-controlled food challenges(Elsevier, 2022) Sabaté-Brescó, M. (Marina); Goikoetxea-Lapresa, M.J. (María José); Gastaminza, G. (Gabriel); Moya, C. (Carmen); Blanca-López, N. (Natalia); Alvarado, M.I. (María Isabel); Quan, P.L. (Paola Leonor); Bartra, J. (Joan); D'Amelio-Garofalo, C.M. (Carmen Mariana); Garcia, B.E. (Blanca Esther); Fernandez, J. (Javier); Ferrer-Cardona, M. (Marta); Pascal, M. (Mariona)Background: As the use of multiplex-specific immunoglobulin E (sIgE) detection methods becomes increasingly widespread, proper comparative validation assessments of emerging new platforms are vital. Objective: To evaluate the clinical and technical performance of a newly introduced microarray platform, Allergy Explorer (ALEX) (MacroArray Diagnostics), in the diagnosis of pollen (cypress, grass, olive), dust mite (Dermato- phagoides pteronyssinus), mold (Alternaria alternata), fruit (apple, peach), and nut (walnut, hazelnut and peanut) allergies and to compare it with those of the ImmunoCAP Immuno Solid-phase Allergen Chip (ISAC) 112 microar- ray and the ImmunoCAP singleplex method (ThermoFisher Scientific). Methods: We enrolled 153 patients with allergy and 16 controls without atopy. The sIgE assays were conducted using ISAC112, ALEX version 2 (ALEX2), and ImmunoCAP for whole extracts and major components. Technical validation of ALEX2 was performed by measuring repeatability and interassay, interbatch, and interlaboratory reproducibility. Results: When measured globally (detection by 1 or more allergen components), ALEX2 had adequate sensitivity and specificity for most of the allergens studied, comparable in general with that of ISAC112 (except for olive pol- len and walnut) and similar to that of ImmunoCAP whole extract measurements. Component-by-component analysis revealed comparable results for all techniques, except for Ole e 1 and Jug r 3, in both ISAC112 and Immu- noCAP comparisons, and Alt a 1, when compared with ISAC112. Continuous sIgE levels correlate with sIgE by ImmunoCAP. Good reproducibility and repeatability were observed for ALEX2. Conclusion: ALEX2 has sound technical performance and adequate diagnostic capacity, comparable in general with that of ISAC112 and ImmunoCAP.
- Usefulness of drug allergy alert systems: present and future(Springer, 2023) Luri-Fernández-de-Manzanos, M. (Marta); Sánchez-Fernández, S. (Sergio); Gastaminza, G. (Gabriel); Ortega-Eslava, A. (Ana); Quan, P.L. (Paola Leonor); Parrado-Gil, L. (Lucía); Calvo-Alonso, A. (Alfonso); Bodero-Sánchez, J.M. (José Miguel)Purpose of Review The goal of this paper is to review drug allergy alert systems (DAAS), to summarise their key components, and to overview potential benefts and challenges associated with these tools. Methods for validation of their effects on patient safety, alternative uses, and strategies to streamline DAAS’ functions and reduce system fatigue are discussed. Recent Findings DAAS are clinical decision support systems (CDSS) that focus on preventing drug adverse events within healthcare settings. The advent of electronic medical records has facilitated the development of digital DAAS. Existing versions use different methods to document diagnosed allergies, and rely on distinct rules and matching strategies for the generation of real-time alerts. DAAS promote the automation of several processes, facilitate prompt patient referral, and may be customised. Information overload, alert overrides by clinicians, and the development of “alert fatigue” may interfere with their usefulness. The newest strategies to streamline the function of DAAS include the use of artifcial intelligence (AI) and other predictive techniques. Summary The rising prevalence of drug allergies underscores the importance of effective DAAS. Further research is needed to evaluate their usefulness, to optimise their performance, to explore different algorithms and data sources, and to enhance the standardised integration of these systems into clinical practice.