HLA-B*1301 Allele Detection for Dapsone Hypersensitivity Risk
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Solution Overview
Problem
There is no reliable method to predict the risk of dapsone hypersensitivity syndrome, a serious drug reaction that can occur in 0.5-3% of patients treated with dapsone, leading to high morbidity and mortality.
Innovation Solution
The use of HLA-B*1301 allele as a genetic marker, detected through PCR-based HLA sequence typing, to identify individuals at higher risk of adverse drug reactions to dapsone, including dapsone hypersensitivity syndrome, and the development of a method to screen candidate drugs that inhibit the expression of the HLA-B*1301 allele for treating such reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dapsone is used to treat infectious diseases and inflammatory conditions, then therapeutic efficacy is improved, but the risk of dapsone hypersensitivity syndrome increases
Solution Approach 1:
The patent applies preliminary action by performing HLA-B*1301 allele detection before dapsone treatment to identify high-risk individuals. This pre-screening allows clinicians to prevent hypersensitivity syndrome by selecting alternative treatments for carriers of the allele, thereby eliminating the harmful effect before it can occur while preserving the therapeutic benefits for non-carriers.
2Measurement precision
If HLA-B*1301 allele detection is implemented to predict dapsone hypersensitivity risk, then prediction accuracy is improved, but detection complexity increases
Solution Approach 1:
The patent applies the extraction principle by isolating and detecting only the specific HLA-B*1301 allele using targeted PCR primers and sequencing methods. Instead of performing comprehensive genomic analysis, the invention extracts and examines only the relevant genetic marker, achieving high prediction accuracy (37.53 to 110.8 times higher risk identification) while maintaining relatively simple and cost-effective detection procedures.
3Object-affected harmful factors
If screening for HLA-B*1301 allele is performed to identify high-risk individuals, then the incidence of dapsone hypersensitivity syndrome is reduced, but the cost and time of treatment planning increase
Solution Approach 1:
The patent implements preliminary action by conducting HLA-B*1301 allele screening before initiating dapsone therapy. This advance detection reduces the incidence of hypersensitivity syndrome by identifying high-risk individuals (37.53 to 110.8 times higher risk) who can be pre-screened and assigned alternative treatments, thereby preventing adverse events before they occur and streamlining treatment planning.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The HLA-B*1301 allele effectively predicts a 37.53 to 110.8 times higher risk of dapsone hypersensitivity syndrome, allowing for targeted treatment alternatives and reducing the incidence of this severe reaction from 1.4% to 0.2% in individuals carrying the allele.
Implementation Method 1
PCR-based HLA sequence typing
Data Source
Figure 1A~1B
Figure 2
AI summary
The present invention discloses uses of a HLA-B*1301 allele, comprising: 1) a use of a substance for detecting whether a person has the HLA-B*1301 allele in preparation of a product for evaluating a risk of adverse drug reactions in response to dapsone in the person; 2) a method for detecting or evaluating a risk of adverse drug reaction in response to dapsone in a person, comprising detecting whether the person has the HLA-B*1301 allele, wherein, a person with LA-B*1301 allele suffers a higher risk of adverse drug reaction upon being administered dapsone, as compared with a person without HLA-B*1301 allele, and a person with LA-B*1301 alleles at both chromosomes of a pair of homologous chromosomes suffers a higher risk of adverse drug reaction upon being administered dapsone, as compared with a person with HLA-B*1301 allele at only one of a pair of homologous chromosomes.