In Vitro and In Vivo Tests for Drug Hypersensitivity Reactions

2018 ◽  
pp. 85-95
Author(s):  
Justin Greiwe ◽  
Jonathan A. Bernstein
2021 ◽  
Vol 12 ◽  
Author(s):  
Violeta Gil-Ocaña ◽  
Isabel M. Jimenez ◽  
Cristobalina Mayorga ◽  
Inmaculada Doña ◽  
Jose Antonio Céspedes ◽  
...  

β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic–inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.


2016 ◽  
Vol 117 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Wei Yann Haw ◽  
Marta E. Polak ◽  
Carolann McGuire ◽  
Michel Erlewyn-Lajeunesse ◽  
Michael R. Ardern-Jones

2021 ◽  
Vol 12 ◽  
Author(s):  
Sean Hammond ◽  
Paul Thomson ◽  
Xiaoli Meng ◽  
Dean Naisbitt

Mitigating the risk of drug hypersensitivity reactions is an important facet of a given pharmaceutical, with poor performance in this area of safety often leading to warnings, restrictions and withdrawals. In the last 50 years, efforts to diagnose, manage, and circumvent these obscure, iatrogenic diseases have resulted in the development of assays at all stages of a drugs lifespan. Indeed, this begins with intelligent lead compound selection/design to minimize the existence of deleterious chemical reactivity through exclusion of ominous structural moieties. Preclinical studies then investigate how compounds interact with biological systems, with emphasis placed on modeling immunological/toxicological liabilities. During clinical use, competent and accurate diagnoses are sought to effectively manage patients with such ailments, and pharmacovigilance datasets can be used for stratification of patient populations in order to optimise safety profiles. Herein, an overview of some of the in-vitro approaches to predict intrinsic immunogenicity of drugs and diagnose culprit drugs in allergic patients after exposure is detailed, with current perspectives and opportunities provided.


2020 ◽  
Vol 10 (4) ◽  
Author(s):  
Yuttana Srinoulprasert ◽  
Ticha Rerkpattanapipat ◽  
Mongkhon Sompornrattanaphan ◽  
Chamard Wongsa ◽  
Duangjit Kanistanon

2019 ◽  
Vol 369 ◽  
pp. 39-48 ◽  
Author(s):  
S.S. Ahmed ◽  
J. Whritenour ◽  
M.M. Ahmed ◽  
L. Bibby ◽  
L. Darby ◽  
...  

2021 ◽  
Vol 42 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Anna R. Wolfson ◽  
Aleena Banerji

Immediate hypersensitivity to drugs is characterized by symptoms such as hives, swelling, and wheezing. To prevent a negative impact on care, assessment by an allergist is important. Evaluation requires a clear clinical history, but it is often lacking or vague, which makes a diagnosis difficult. Allergists instead can use skin testing and drug challenge to evaluate drug hypersensitivity reactions, which help the patient and provider understand the causative drug(s) and, more importantly, enables the use of the exonerated drug(s). Although penicillin skin testing is standardized, well described, and widely used, skin testing for most other drugs requires the use of a nonirritating skin testing concentration that can have a low negative predictive value. Drug challenges are the criterion standard for confirming tolerance. The allergist must obtain an in-depth clinical history and then follow with skin testing and/or drug challenges when indicated to determine which drugs can be de-labelled and which should be avoided. In this review, we focused on the evaluation of drug hypersensitivity reactions to antibiotics, perioperative agents, biologics, and chemotherapeutics.


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