Human leukocyte antigens (HLAs) are an essential part of the immune system, influencing how the body identifies “self” and “non-self.” Understanding HLA genetic testing is vital for practitioners integrating this testing into their practice, especially as it applies to specific conditions like celiac disease or sensitivity to mould exposure. This blog will explore the basics of HLAs, the different testing methods, and how to interpret these results to benefit your clients.
What are HLAs?
HLAs are proteins present on the surface of white blood cells and other nucleated cells, playing a critical role in the immune system’s ability to differentiate between “self” and “foreign” cells. This process ensures that cells identified as “foreign” trigger an immune response, making HLAs a cornerstone in immune health. HLAs are highly polymorphic, with numerous alleles that fine-tune the adaptive immune system to fight infections, manage autoimmunity, and facilitate tissue compatibility for organ transplants.
HLA Genetic Testing: Overview
HLA genetic testing identifies the specific HLA genes an individual has inherited and their corresponding antigens. Traditionally, the primary use of HLA testing has been in matching organ or tissue transplant donors and recipients. However, HLA testing can also be relevant in assessing autoimmune conditions and certain disease risks. Some HLA alleles are associated with sensitivities to medications and environmental factors, such as mould exposure or gluten intolerance.
Differences in HLA Testing and Result Formats
When practitioners order HLA genetic tests from different providers, they may receive results in varying formats. This variation is due to differences in testing methodologies and nomenclature used across labs. The two most common techniques practitioners may encounter are:
- SNP Testing with Array-Based Methods: This technique focuses on identifying specific single nucleotide polymorphisms (SNPs) within the HLA gene. These tests are generally faster and less expensive. SNP testing provides results like HLA-DQ2.5 CT or HLA-DQ8 TT, indicating the presence of particular SNPs linked to HLA-DQ2 or HLA-DQ8. These results show whether specific SNP variations are present in a person’s DNA, which is useful for initial risk assessment or when testing large populations for celiac disease predisposition.
- Real-Time PCR for Direct Qualitative Detection: Most pathology services use this method, which provides a detailed breakdown of the HLA gene, offering results such as DQA1*02 or DQA1*05, indicating specific alleles within the HLA-DQ region. This level of detail is important in cases where more precise allele identification is needed, such as in organ transplantation, but it may not add additional clinical utility compared to SNP-based tests for some conditions.
Each technique is valid, and it is important that practitioners are aware of these differences to understand the varying result outputs of the two tests.
Integrating HLA DNA Insights into Practice: examples
Celiac Disease
Celiac disease is one of the primary conditions where HLA testing is applied. The presence of the HLA-DQ2 or HLA-DQ8 alleles is strongly associated with celiac disease. However, it’s important to note that while most individuals with celiac disease carry one of these alleles, not everyone who has the alleles will develop the condition. The presence of these alleles indicates a genetic predisposition but does not confirm an active disease. Only about 3% of individuals with HLA-DQ2 or HLA-DQ8 go on to develop celiac disease, so regular monitoring is advised for those at risk.
Mould Exposure Sensitivity
Some HLA alleles, specifically the HLA-DR and HLA-DQ isotypes, are linked to mould toxin sensitivity. Approximately 24% of the population has a genetic susceptibility to mould-related illness due to these alleles, making them less able to mount an appropriate immune response to mould toxins. Identifying these genetic weaknesses can guide personalized management strategies for patients exposed to mould, including interventions to reduce toxin exposure or enhance detoxification.
Conclusion: Interpreting HLA Test Results
HLA genetic testing provides powerful insights into immune health, autoimmune disease risk, and environmental sensitivities, such as celiac disease and mould exposure. However, it is a complex topic, and practitioners must be aware of its limitations. While the presence of certain HLA alleles can indicate genetic predispositions, such as HLA-DQ2 for celiac disease or HLA-DR for mould sensitivity, these results do not guarantee disease onset or a definitive outcome. It’s crucial to interpret HLA test results within the broader context of clinical assessments and patient history. By understanding the nuances of HLA polymorphisms and their applications, practitioners can use this testing to offer more personalized care, while recognizing the importance of combining genetic data with other clinical factors for well-rounded recommendations.
