Human Leukocyte Antigens and Adverse Drug Reactions: Towards Safer Pharmacotherapy

About the Study

Adverse Drug Reactions (ADRs) remain a significant challenge in modern pharmacotherapy, leading to increased morbidity, hospitalizations and healthcare costs. The variability in individual responses to medications can often be traced to genetic factors, particularly those involving Human Leukocyte Antigens (HLAs). These molecules, which play an important role in the immune system, are linked to various ADRs, especially in the context of hypersensitivity reactions. Understanding the relationship between HLAs and ADRs can provide insights into personalized medicine, enabling the identification of patients at risk and the development of strategies to mitigate adverse outcomes.

Human leukocyte antigens are a group of proteins encoded by the Major Histocompatibility Complex (MHC) on chromosome 6. They are essential for the regulation of the immune response, facilitating the presentation of peptide fragments to T cells. Variations in Human Leukocyte Antigen (HLA) genes can influence individual susceptibility to drug-induced hypersensitivity reactions. For instance, specific HLA alleles have been associated with severe skin reactions, such as Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), particularly in patients treated with certain medications, including allopurinol, carbamazepine and nevirapine. In these cases, the presence of particular HLA alleles, such as HLA-B1502 and HLA-A3101, has been linked to an increased risk of these life-threatening reactions. Such associations highlight the importance of genetic screening in identifying individuals who may be at higher risk for ADRs, allowing for more informed prescribing practices.

The role of HLAs in drug hypersensitivity is not limited to skin reactions; they are also implicated in other types of ADRs, including drug-induced liver injury and hematological disorders. For example, HLA-B*5701 is associated with hypersensitivity to the antiretroviral drug Abacavir, leading to potentially severe reactions in predisposed individuals. In these cases, preemptive HLA testing can be beneficial in clinical practice. Identifying patients carrying specific HLA alleles allows healthcare providers to avoid administering drugs that could provoke serious ADRs, thereby improving patient safety and treatment outcomes [1-4].

The integration of pharmacogenetic testing into clinical practice is gaining traction, but challenges remain. While the association between specific HLA alleles and ADRs is well-established, routine screening is not yet standard in many healthcare settings. Barriers to implementation include the need for increased awareness among healthcare professionals, the availability of genetic testing and the incorporation of results into clinical decision-making processes. Furthermore, there is a need for comprehensive guidelines to facilitate the interpretation of HLA testing results, ensuring that healthcare providers can make informed decisions based on genetic data.

Educating healthcare professionals about the significance of HLAs in drug reactions is essential for enhancing patient safety. Continuous professional development and training programs can help clinicians understand the implications of genetic variations on drug metabolism and response. By fostering a greater understanding of the connection between HLAs and ADRs, healthcare providers can engage in shared decision-making with patients, empowering them to make informed choices about their treatment options [5,6].

In conclusion, the association between human leukocyte antigens and adverse drug reactions underscores the importance of considering genetic factors in pharmacotherapy. By recognizing the role of HLAs in drug hypersensitivity, healthcare providers can implement more personalized approaches to medication management, thereby reducing the risk of ADRs [7-10]. As pharmacogenomic testing becomes more widely available and integrated into clinical practice, the potential to improve patient outcomes through tailored therapeutic strategies will become increasingly attainable. This shift towards precision medicine holds promise for enhancing the safety and efficacy of drug therapies, ultimately leading to better health outcomes for patients.

References

1. Tobaiqy M, et al. Views of parents and pharmacists following participation in a paediatric pharmacovigilance study. Pharm World Sci. 2010;32:334-338.

   [Crossref] [PubMed] [Google scholar]

2. Alghadeer S, et al. The patterns of children poisoning cases in community teaching hospital in Riyadh, Saudi Arabia. Saudi Pharm J. 2018;26:93‐97.

   [Crossref] [PubMed] [Google Scholar]

3. Alruwaili ND, et al. An epidemiological snapshot of toxicological exposure in children 12 years of age and younger in Riyadh. Ann Saudi Med. 2019;39:229‐235.

   [Crossref] [PubMed] [Google scholar]

4. Hoy JL, et al. Unintentional poisoning hospitalisations among young children in Victoria. Inj Prev. 1999;5:31‐35.

   [Crossref] [PubMed] [Google Scholar]

5. Al-Shehri M. Pattern of childhood poisoning in Abha City-Southwestern Saudi Arabia. J Family Community Med. 2004;11:59-63. 

   [PubMed] [Google Scholar]

6. OM Al Madni, et al. Hanging deaths in Dammam, Kingdom of Saudi Arabia. J Forensic Leg Med. 2010;17:265-268.

   [Crossref] [PubMed] [Google Scholar]

7. Verma N, et al. Formulation and evaluation of herbal depilatory cream. Pharmacologyonline. 2011;3:674-683.
8. Newall CA, et al. Herbal medicines. A guide for health-care professionals. London: The Pharmaceutical Press. 1996.

   [Google Scholar]

9. Kumar V, et al. Pharmacognostic and pharmacological evaluation of eulaliopsis binata plant extracts by measuring in vitro/in vivo safety profile and anti-microbial potential. Toxicol Res. 2018;7:454-464.

   [Crossref] [Google Scholar]

10. Mohan C, et al. A comparative study of SARS, MERS with COVID-19. Coronaviruses. 2021;2:364-368.

    [Crossref]