Biomarkers of immediate drug hypersensitivity Mayorga, Cristobalina; Ariza, Adriana; Muñoz‐Cano, Rosa ...
Allergy (Copenhagen),
March 2024, 2024-Mar, 2024-03-00, 20240301, Letnik:
79, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Immediate drug hypersensitivity reactions (IDHRs) are a burden for patients and the health systems. This problem increases when taking into account that only a small proportion of patients initially ...labelled as allergic are finally confirmed after an allergological workup. The diverse nature of drugs involved will imply different interactions with the immunological system. Therefore, IDHRs can be produced by a wide array of mechanisms mediated by the drug interaction with specific antibodies or directly on effector target cells. These heterogeneous mechanisms imply an enhanced complexity for an accurate diagnosis and the identification of the phenotype and endotype at early stages of the reaction is of vital importance. Currently, several endophenotypic categories (type I IgE/non‐IgE, cytokine release, Mast‐related G‐protein coupled receptor X2 (MRGPRX2) or Cyclooxygenase‐1 (COX‐1) inhibition and their associated biomarkers have been proposed. A precise knowledge of endotypes will permit to discriminate patients within the same phenotype, which is crucial in order to personalise diagnosis, future treatment and prevention to improve the patient's quality of life.
Cofactors in food anaphylaxis in adults Bartra, Joan; Turner, Paul J; Muñoz-Cano, Rosa M
Annals of allergy, asthma, & immunology,
06/2023, Letnik:
130, Številka:
6
Journal Article
Recenzirano
Around 25% to 50% of food-induced allergic reactions in adults cause anaphylaxis, and epidemiologic evidence suggests that food is the most common cause of anaphylaxis. Reaction severity is ...unpredictable, and patients will often experience reactions of variable severity, even to an identical exposure (both dose and allergen). A common explanation for this phenomenon has been the impact of "cofactors"-factors that might contribute to reaction severity independent of the allergen exposure. Cofactors can influence reaction severity in 2 ways: either by reducing the reaction threshold (ie, the dose needed to trigger any symptoms) so that patients have no symptoms in the absence of the cofactor and only react with the cofactor present, or by increasing reaction severity such that individuals have only mild symptoms in the absence of the cofactor, but a more severe reaction when the cofactor is present. Indeed, the same patient may have reactions with different cofactors or even need more than one cofactor to develop a severe reaction. Cofactors reportedly play a role in approximately 30% of anaphylaxis reactions in adults. Exercise, nonsteroidal, anti-inflammatory drugs, alcohol, and sleep deprivation are the most frequent cofactors reported. Routine evaluation of the possible involvement of cofactors is essential in managing patients with food anaphylaxis: in patients with a suggestive history but a negative oral food challenge, cofactors should be taken into account to provide appropriate advice to reduce the risk of future anaphylaxis.
Background
Recent studies show that nsLTP sensitization is not limited to the Mediterranean basin and can present diverse clinical phenotypes. It remains challenging to predict clinical outcome when ...specific IgE antibodies (sIgE) to nsLTPs are present. This study compares both clinical and in vitro allergy characteristics but also diagnostic performance of a basophil activation test (BAT) and sIgG4 in nsLTP‐sensitized patients from Antwerp (ANT, Belgium) and Barcelona (BCN, Spain).
Methods
Adult subjects with positive sIgE rPru p 3 and/or rMal d 3 ≥ 0.10 kUA/L (n = 182) and healthy controls (n = 37) were included. NsLTP‐sensitized individuals were stratified according to clinical symptoms with peach/apple, respectively. BAT rPru p 3 and rMal d 3 were performed and sIgG4 antibodies to both components quantified.
Results
In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 (0.001 µg/mL) can identify clinically relevant Mal d 3 sensitization (sensitivity of 60%‐63% and a specificity of 75%‐67%, respectively). In ANT, only the sIgE/total IgE rPru p 3 ratio shows added value (sensitivity 60% and specificity 83%). Finally, it appears that symptomatic patients in BCN are more sensitive to lower allergen concentrations compared to ANT. In addition, it was shown that ANT patients were more often sensitized to pollen and that specific pollen sources differed between regions.
Conclusions
NsLTP‐related allergy profiles and diagnostic performance differ significantly between regions and are component‐specific, which makes extrapolation of data difficult to do. In addition, it seems that basophil sensitivity might show geographical differences. Additional research is needed to confirm these findings.
This study explores the performance of BAT, sIgE/total IgE, sIgG4 and sIgG4/sIgE ratio in Pru p 3‐ and Mal d 3‐sensitized populations from Antwerp (ANT) and Barcelona (BCN). In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 can identify clinically relevant Mal d 3 sensitization, whereas in ANT, only the sIgE/total IgE rPru p 3 ratio shows added value. NsLTP sensitization and diagnostic performance cannot be extrapolated from one population to another. BAT, basophil activation test; nsLTP, nonspecific lipid transfer protein.
Background
In up to 70%–80% of patients with a suspected non‐steroidal anti‐inflammatory drug hypersensitivity (NSAIDH), challenge tests with the culprit drug yield negative results. On the other ...hand, there could be a NSAIDH overdiagnosis when anaphylaxis is the clinical manifestation. We hypothesize that some negative NSAID challenge tests and an overdiagnosis of NSAIDH occur in patients with food‐dependent NSAID‐induced hypersensitivity (FDNIH).
Methods
We studied 328 patients with a suspected acute NSAIDH. FDNIH was diagnosed in patients meeting all the following: (1) tolerance to the food ingested more temporally closed before the reaction, later the episode, (2) respiratory or cutaneous symptoms or anaphylaxis related to NSAID, (3) positive skin prick test to foods and/or specific IgE to food allergens (Pru p 3, Tri a 19, Pen a 1) involved in the reaction, and (4) negative oral provocation test to the culprit NSAID.
Results
199 patients (60%) were diagnosed with NSAIDH and 52 (16%) with FDNIH. Pru p 3 was involved in 44 cases (84.6%) and Tri a 19 in 6 cases (11%). FDNIH subjects were younger (p < .001), with a higher prevalence of rhinitis (p < .001) and previous food allergy (p < .001), together with a higher proportion of subjects sensitized to pollens (p < .001) and foods (p < .001). Using just four variables (Pru p 3 sensitization, Tri a 19 sensitization, anaphylaxis, and any NSAID different from pyrazolones), 95.3% of cases were correctly classified, with a sensitivity of 92% and specificity of 96%.
Conclusion
Evaluation of FDNIH should be included in the diagnostic workup of NSAIDH.
16% of patients with suspicion of acute NSAID hypersensitivity were diagnosed as FDNIH reactions being lipid transfer protein (Pru p 3) the main food allergen involved. With four variables (Pru p 3 or Tri a 19 sensitization, anaphylactic reaction and any NSAID involved different from a pyrazolone), FDNIH is correctly diagnosed in 95.3% of cases (92% of sensitivity, 96% of specificity). These observations support the relevance of individualized assessment of both NSAID hypersensitivity and food allergy in patients with suspected acute NSAID hypersensitivity.
Abbreviations: FDNIH, food‐dependent NSAID‐Induced hypersensitivity; NSAID, non‐steroidal anti‐inflammatory drug
The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately ...half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a β-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of β-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology.
Background
Patients with peach allergy due to nsLTP sensitization constitute a heterogeneous group in terms of sensitization profile and severity. This could be due to the presence of additional ...allergies to pollens. The aim of this study was to analyse the clinical characteristics, sensitization profile and severity of reactions in peach‐allergic patients sensitized to nsLTP from two Mediterranean areas with different pollen exposure.
Methods
Patients with diagnosis of LTP allergy from the Allergy Unit of Hospital Regional Universitario de Malaga (HRUM) and Hospital Clinic de Barcelona (HCB) were prospectively included and classified into two groups; (a) LTP‐monoallergic: those that presented reaction only with peach and (b) LTP‐Allergy: those that presented reaction with peach and at least another plant‐food containing LTP.
Results
A total of 252 patients were included, 235 (93.2%) had LTP‐syndrome and 17 (6.8%) were LTP‐monoallergic. We found a higher percentage of anaphylaxis and delayed onset of symptoms in the LTP‐monoallergic group (P = .02 and P = .04, respectively). Moreover, anaphylaxis was less frequent in patients with profilin sensitization (P = .03). The comparison of patients' data from HRUM with data from HCB showed differences in sensitization to olive tree pollen and profilin (P = .01 and P = .001, respectively).
Conclusion
This study was undertaken to characterize two large group of subjects from to two regions with differing exposures to pollen. We found that more than 90% of peach‐allergic patients in both populations evolved to LTP‐Allergy and showed an early onset. Profilin sensitization could be more useful as a severity biomarker than the number of nsLTP, aeroallergen sensitizations or sIgE levels. This could provide clues regarding sensitization and severity patterns that might be relevant in other geographical areas.
Most LTP‐dependent peach‐allergic patients with an early onset end up suffering from an LTP‐syndrome. An early intervention could potentially reduce the risk of developing an LTP‐syndrome. Pollen sensitization profiles could be used as a severity biomarker. Abbreviation: LTP, lipid transfer protein 屁
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