Question 1

What is the Meaning of HLA-B 57: 01?

Accepted Answer

HLA-B57:01 identifies a specific allele of the Human Leukocyte Antigen B gene, a critical component of the major histocompatibility complex (MHC) class I system. This particular genetic variant is recognized for its strong association with immunological reactions to certain pharmaceutical agents. It represents a precise genetic marker within an individual's unique genomic profile.

Question 2

What is the Context of HLA-B 57: 01?

Accepted Answer

This allele operates within the sophisticated framework of the adaptive immune system, situated on the surface of nearly all nucleated cells in the body. Its primary function involves presenting intracellular peptide fragments to cytotoxic T lymphocytes, enabling the immune system to distinguish between healthy self-cells and those infected or abnormal. The presence of this specific allele significantly impacts an individual's immune surveillance capabilities and their predisposition to certain drug-induced hypersensitivity reactions.

Question 3

What is the Significance of HLA-B 57: 01?

Accepted Answer

The presence of the HLA-B57:01 allele holds considerable clinical importance as a pharmacogenomic indicator, particularly in the management of human immunodeficiency virus (HIV) infection. Individuals who carry this allele face a substantially elevated risk of developing a severe, potentially life-threatening hypersensitivity reaction to abacavir, a widely used antiretroviral medication. Pre-treatment genetic screening for this allele is a standard clinical practice, designed to prevent adverse drug events and safeguard patient well-being.

Question 4

What is the Mechanism of HLA-B 57: 01?

Accepted Answer

The mechanism underlying abacavir hypersensitivity in HLA-B57:01 positive individuals involves a unique interaction where abacavir or its metabolites bind non-covalently within the peptide-binding groove of the HLA-B57:01 molecule. This binding alters the conformation of the HLA molecule, causing it to present a novel set of self-peptides that are then recognized as foreign by circulating CD8+ T cells. This aberrant presentation triggers a robust, systemic T-cell mediated immune response, culminating in the characteristic clinical syndrome of hypersensitivity.

Question 5

What is the Application of HLA-B 57: 01?

Accepted Answer

The clinical application of HLA-B57:01 testing involves mandatory genotyping of patients before initiating therapy with abacavir for HIV. A positive test result for this allele serves as a definitive contraindication for abacavir use, necessitating the selection of alternative antiretroviral regimens. This proactive genetic screening measure has proven highly effective in virtually eliminating the incidence of abacavir-induced hypersensitivity reactions in clinical practice, thereby enhancing patient safety and optimizing treatment outcomes.

Question 6

What is the Metric of HLA-B 57: 01?

Accepted Answer

The determination of HLA-B57:01 status is achieved through molecular genetic testing, typically performed on a blood sample. Laboratory techniques such as polymerase chain reaction (PCR) or DNA sequencing are employed to identify the specific genetic sequence corresponding to this allele. The result is a clear positive or negative, which directly informs clinical decision-making regarding the suitability of abacavir therapy for a given patient.

Question 7

What is the Risk of HLA-B 57: 01?

Accepted Answer

The primary clinical risk associated with a positive HLA-B57:01 status is the potential for a severe, multi-systemic hypersensitivity reaction upon exposure to abacavir. This reaction can manifest with symptoms including fever, rash, gastrointestinal disturbances, respiratory compromise, and generalized malaise, with the potential for progression to organ dysfunction if the medication is not promptly discontinued. Re-exposure to abacavir in an individual previously sensitized due to HLA-B57:01 positivity can precipitate a rapid and severe, life-threatening immunological response.

HLA-B 57: 01

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

Can Genetic Screening Fully Eliminate Adverse Reactions to Peptide Therapies?

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