Identification of T‐cell epitopes from benzylpenicillin conjugated to human serum albumin and implication in penicillin allergy

Azoury, Marie Eliane; Filì, Lucia; Bechara, Rami; Scornet, Noémie; Chaisemartin, Luc de; Weaver, Richard J.; Claude, Nancy; Maillère, Bernard; Parronchi, Paola; Joseph, Delphine; Pallardy, Marc

doi:10.1111/all.13418

Cited by 30 publications

(57 citation statements)

References 37 publications

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“…This test measures the T cell proliferation to a drug in vitro, from which one can simulate a previous in vivo reaction against a drug sensitization. Lymphocyte transformation test has been widely implemented for medical diagnosis of immunodeficiency, pathogenic diseases, and type IV allergy (40,41). The Rainger and Rowley (42) was used to determine the serum bactericidal activity to Aeromonas hydrophila strain, and the results were expressed as survival index.…”

Section: Immune Indicesmentioning

confidence: 99%

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

et al. 2020

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This study was executed to investigate the effect of supplementing three multienzyme levels (0, 0. 1, and 0.2%) with two types of diet [standard diet (SD) vs. low-density diet (LDD)] on immune response, blood hematology and biochemistry, antioxidant status, and organ histology of broilers during 1-38 days of age. A total of 216 unsexed 1-day-old Arbor Acres broiler chicks were randomly distributed, on a factorial design (2 × 3), to six treatments each with six replicates. There were six chicks per replicate. Results showed that LDD significantly decreased body weight gain (BWG) of broilers, but did not affect the European Production Efficiency Index (EPEI). Addition of multienzymes at both levels (0.1 and 0.2%) significantly increased BWG and improved EPEI, compared to the control diet. Alanine aminotransferase (ALT), aspirate aminotransferase (AST), malondialdehyde (MDA), lymphocyte, lymphocyte transformation test (LTT), and phagocyte activity (PA) were significantly higher for LDD than the SD, but eosinophil was lower. Supplementation of multienzymes significantly decreased ALT, AST, and MDA, compared to the control group, but increased packed cell volume (PCV), hemoglobin (Hgb), lymphocytes, and monocytes. Immune organs, such as spleen, thymus, and the bursa of Fabricius were significantly increased with multienzyme supplementation. It could be concluded that multienzyme supplementation at either 0.1 or 0.2% to SD or LDD improved EPEI and immune status of broiler chicks.

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Section: Immune Indicesmentioning

confidence: 99%

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

et al. 2020

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“…Recently, important advances have been performed regarding the understanding of sensitization and haptenation process of BLs. A study has identified two target peptides of human serum albumin (HSA) for benzylpenicillin, to which this drug was covalently bound on lysines 159 and 525, which were able to induce specific proliferation of T cells from BL‐allergic patients . Another study has suggested that patients could be immunized by benzylpenicillin‐haptenated peptides from proteins generated in dendritic cells during the processing and presentation to T cells .…”

Section: New Understanding Of Dhr Mechanismmentioning

confidence: 99%

“…A study has identified two target peptides of human serum albumin (HSA) for benzylpenicillin, to which this drug was covalently bound on lysines 159 and 525, which were able to induce specific proliferation of T cells from BL-allergic patients. 140 Another study has suggested that patients could be immunized by benzylpenicillin-haptenated peptides from proteins generated in dendritic cells during the processing and presentation to T cells. 141 Moreover, CLV binds to Lys 195 and 475 residues of HSA, forming adducts able to activate basophils in 69% of CLV-allergic patients.…”

Section: Ige-mediated Reactionsmentioning

confidence: 99%

Recent developments and highlights in drug hypersensitivity

Mayorga

Fernandez

Montañez

et al. 2019

Allergy

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Drug hypersensitivity reactions (DHRs) are nowadays the third cause of allergy after rhinitis and asthma with a significant increase in prevalence in both adults and paediatric population with new drugs included as culprit. For this, DHRs represent not only a health problem but also a significant financial burden for affected individuals and health systems. Mislabelling DHRs is showing to be a relevant problem for both, false label of drug allergic and false label of nonallergic. All this reinforces the need to improve accurate diagnostic approaches that allow an appropriate management.Moreover, there is a need for training both, nonallergist stakeholders and patients to improve the reaction identification and therefore decrease the mislabelling. The use of allergy cards has shown to be relevant to avoid the induction of DHRs due to the prescription of wrong medication.Recent developments over the last 2 years and highlights about risk factors, diagnostic approaches, mechanisms involved as well as prevention actions, and management have been reviewed. In these papers, it has been outlined the need for correct diagnosis and de-labelling of patients previously false-reported as allergic, which will improve the management and treatment of patients with DHRs. K E Y W O R D Sallergy diagnosis, allergy treatment, basic mechanisms, drug allergy, epidemiology | 2369

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“…We have also recently identified BP‐haptenated peptides from HSA that can activate naïve CD4+ T cells . Two of these BP‐haptenated peptides were also found to induce PBMCs proliferation in allergic patients confirming their role in patients immunization …”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of a naïve CD8+ T cell repertoire for benzylpenicillin

Bechara

Maillère

Joseph

et al. 2019

Clin Experimental Allergy

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Background: Beta-lactams allergy is the most commonly reported drug allergy and constitutes an important health problem. We previously showed the pre-existence of a naïve CD4+ T cell repertoire for benzylpenicillin (BP) coupled to human serum albumin (HSA) but little is known about the naïve CD8+ T cell repertoire specific for BP.Objective: The purpose of this work was to identify naïve CD8+ T cells specific for BP and to explore mechanisms dictating their activation.Methods: Co-cultures were established with naïve CD8+ T cells and autologous dendritic cells (DCs) loaded with HSA-BP or free BP. T cells were restimulated once a week with autologous DCs loaded with HSA-BP or BP. The specific CD8+ T cell response was measured using an IFN-γ ELISpot assay.Results: When using free BP, we were able to detect a naïve CD8+ T cell repertoire for BP in the 6 out of 7 tested healthy donors. However, our results showed that HSA-BP was recognized by naïve CD8+ T cells in only one donor out of five tested healthy donors. Using free BP, we evidenced its binding to cellular proteins in DCs that was concentration dependent and was correlated with BP-specific CD8+ T cell activation. Moreover, the BP-specific CD8+ cell response was MHC class I-dependent and required intracellular processing and proteasome activity. Conclusion and clinical relevance:This work showed the existence of a naïve CD8+ T cell repertoire for BP when DCs were treated with free BP suggesting that patients could be immunized by haptenated peptides from cellular proteins generated in antigen-presenting cells.

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Identification of T‐cell epitopes from benzylpenicillin conjugated to human serum albumin and implication in penicillin allergy

Abstract: This study identifies and characterizes for the first time the BP-haptenated peptides from HSA involved in the immunization of patients to penicillins.

Cited by 30 publications

References 37 publications

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

Effect of Different Levels of Multienzymes on Immune Response, Blood Hematology and Biochemistry, Antioxidants Status and Organs Histology of Broiler Chicks Fed Standard and Low-Density Diets

Recent developments and highlights in drug hypersensitivity

Identification and characterization of a naïve CD8+ T cell repertoire for benzylpenicillin

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