Genomic Study of Genetic Polymorphisms Involved in Immediate Allergic Reactions to Beta-lactam Antibiotics

Study Overview
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Brief Summary
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Beta-lactam antibiotics include penicillin and cephalosporins and are among the most prescribed antibiotics. This category of drugs is the most involved in immediate allergic manifestations with 2% reactions in treated subjects and a fatal outcome in 1/50000 treatments. Reactions are IgE-mediated and have a considerable but unknown genetic origin, revealed by studies in groups of different ethnical origins in the same geographical region. There are also some families with a high frequency of allergic reactions without identified Mendelian inheritance. The purpose of this study is to identify predictive risk factors associated to immediate allergic reactions against beta-lactam antibiotics with a pangenomic approach. A secondary purpose is to identify rare predictive factors with homozygosity mapping and exome sequencing in various families with high risk of allergy to beta-lactam antibiotics.

Official Title
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Genomic Study of Genetic Polymorphisms Involved in Immediate Allergic Reactions to Beta-lactam Antibiotics

Conditions
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Beta-Lactams Allergy, Hypersensitivity

Intervention / Treatment
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* Other: Collection of blood sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Allergy group: Immediate allergic reaction (less than 2 hours after drug administration) to an antibiotic of penicillin or cephalosporin groups Allergy group: Positive skin test (intradermal test) with a non-irritant dilution of antibiotic of penicillin or cephalosporin groups Exclusion Criteria: Refusal of participation
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Beta-lactam antibiotic allergy<br>Diagnosis based on clinical symptomatology and skin test positive for allergen and negative for other drugs and substances. Skin tests are performed 6 weeks after allergic reaction. | Other: Collection of blood sample<br> <br> |
| Control<br>No specific clinical investigation for control subjects | Other: Collection of blood sample<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of genetic polymorphisms predictive of risk of beta-lactam immediate allergy | Common (>10%) or rare (1-10%) genetic polymorphisms in patients with beta-lactam immediate allergy | day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of allelic homozygosity linked to allergen response, in more than 2 allergic individuals of the same family | Allelic homozygosity in one or more regions of genome with one or more genes involved in allergen response, in more than 2 individuals affected by beta-lactam allergy in the same family | day 0 | 
| Severity of allergic reaction | evaluated during clinical examination | day 0 | 
| Reactivity to skin test |  | day 0 | 
| Serum concentration of specific IgE |  | day 0 |