HLA-B-21M/T Dimorphism Linked to Reduced COVID-19 Severity

Medical News: Genetic Link to COVID-19 Severity
A recent study reveals that genetics may hold key insights into why some people experience milder COVID-19 symptoms than others. This discovery centers on a specific genetic marker, known as the HLA-B-21M/T dimorphism, which affects the immune response of natural killer (NK) cells. Researchers at Karolinska Institutet in Sweden, along with collaborators from the Icahn School of Medicine at Mount Sinai in New York and the University of Oslo, studied 230 unvaccinated COVID-19 patients to understand how this gene variant might influence disease severity.


HLA-B-21M/T Dimorphism Linked to Reduced COVID-19 Severity

This Medical News report takes a closer look at the findings and how they might open doors to new ways of managing COVID-19 and similar viral infections.
 
Uncovering HLA-B-21M/T’s Role in COVID-19
The HLA-B gene has a variant at position –21, known as the HLA-B-21M/T dimorphism. This genetic difference can determine whether a person’s NK cells, a part of the immune system, will react strongly against infected cells or with a more moderate response. The variant has two forms: “M” for methionine and “T” for threonine. Each person inherits two copies of this gene, creating combinations such as M/M, M/T, or T/T.
 
The study revealed that individuals with the M/M genotype (two methionines) showed a greater capacity to handle COVID-19 with less severity. These findings suggest that the M/M genotype might allow NK cells to attack the virus more effectively and limit disease progression. This discovery helps scientists understand the role that HLA-B variants could play in protecting against severe respiratory diseases.
 
Study Highlights: Fewer Severe Cases in M/M Genotype Carriers
Researchers found that only 6% of patients with moderate COVID-19 symptoms had the M/M genotype, while just 0.9% of severe cases carried this genetic combination. This suggests that having two M variants could provide a stronger, more coordinated immune response against COVID-19, possibly reducing the need for intensive treatments.
 
When comparing age- and sex-matched groups, they noted that M/M individuals were less likely to require mechanical ventilation and displayed better health outcomes than their T/T or M/T counterparts. This protective effect was even more pronounced after analyzing multiple clinical markers such as lymphocyte levels and anti-viral protein IFN-γ, a crucial cytokine in fighting infections. Elevated levels of IFN-γ were noted in M/M individuals, which may boost their immune response.
 
COVID-19 Severity and Immune Markers: A New Disease Signature
The study also examined multiple clinical indicators, forming a disease signature that revealed the clear benefit for M/M patients. Those with M/M genotypes generally had higher lymphocyte counts and lower neutrophil-to-lymphocyte ratios, both indicators of a less severe disease course. Principal component analysis, a statistical method used to visualize complex data, showed that patients with M/M genotypes tended to group in less severe clusters based on their clinical markers, while T/T and M/T patients had more scattered and severe disease presentations.
 
In other words, the unique combination of clinical data points confirms that M/M genotype carriers have a lower chance of developing severe COVID-19 symptoms. With NK cells enhanced by the M/M variant, they are able to effectively curb the virus, resulting in fewer cases needing advanced respiratory support.
 
What This Means for Future COVID-19 Research and Treatments
The implications of this study are intriguing. If further research confirms the protective effect of the M/M genotype in COVID-19, it could pave the way for new therapies that target or mimic the immune activity seen in these individuals. There’s potential to develop treatments that enhance NK cell responses, offering a targeted approach that could work alongside vaccines and other immune-boosting strategies.
 
By understanding the genetic makeup that aids in milder disease outcomes, researchers may also be able to identify high-risk individuals based on their genetic profiles. This could allow healthcare providers to better anticipate which patients are likely to experience severe COVID-19 and offer more personalized care.
 
A Closer Look at NK Cells and Their Vital Role
NK cells play a critical role in the immune system, especially in recognizing and attacking virus-infected cells. For people with the M/M genotype, NK cells are more responsive due to the increased availability of peptides that bind to HLA-E, an immune system molecule that interacts with the NK cell receptor NKG2A. This interaction primes NK cells, giving them a stronger ability to attack virus-infected cells when activated.
 
Interestingly, the study indicates that COVID-19 may not only be managed through vaccination but also through genetic and immunological pathways, such as NK cell enhancement. Targeting these cells might be a promising area for treating those who do not respond well to vaccines or other treatments.
 
Conclusion: Hope for Future Genetic-Based Interventions
This research offers a valuable insight into how our genetic code can affect the severity of COVID-19, specifically through the role of the HLA-B-21M/T dimorphism and its effect on NK cell functionality. Patients with the M/M variant appear to have a genetic advantage, with NK cells primed to respond more vigorously to the virus. By elevating levels of IFN-γ, the immune response in these individuals seems more robust, potentially preventing the progression to severe disease.
 
The findings underscore the importance of continued genetic research to better understand disease mechanisms and improve healthcare outcomes. While the path to a full understanding of how genes influence COVID-19 severity is ongoing, this study marks a significant step. Looking ahead, genetic insights may help in developing treatments that could be tailored to individuals’ unique immune profiles, ultimately leading to more effective responses against COVID-19 and similar infections.
 
The study findings were published in the peer-reviewed journal: Genes & Immunity.
https://link.springer.com/article/10.1038/s41435-024-00302-6
 
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