Monday, September 30, 2013

Correlation between HLA alleles and pH1N1 mortality rates

            Many people have had the flu at last once in their life and see their doctors every year for a flu vaccination.  The vaccine is typically trivalent, which means that it protects against three different strains of the influenza virus: H1N1, H3N2, and an influenza B strain.  This vaccine is given as an intradermal shot meaning it is injected into the skin instead of the muscle2.  Seeing as how flu season is fast approaching I though it fitting to bring to light an article relating the flu, or more specifically the pandemic influenza A virus strain (pH1N1) of the 2009-2010 flu season.  However, before delving into the article I would like to provide the basic, necessary background information.

            When an antigen is engulfed by an antigen presenting cell (APC), its proteins are broken down and a small peptide chain of about 10 base pairs is expressed so that activated cytotoxic T-cells can destroy the infected cell3.  The proteins that express these peptides are called MHC (major histocompatabiltiy complex) class I and MHC class II proteins which are encoded by the human leukocyte antigen (HLA) gene3.  For MHC class I gene on HLA there are three regions: HLA-A, HLA-B, and HLA-C for which many different alleles exist3.  Some MHC alleles display the peptides for T-cell recognition better than others which is why different people have different immune responses to the same pathogen.  

Additionally, CD8+ is the specific receptor that MHC class I binds to on T-cells3.  Infected cells also release interferons (INFs) that increases the expression of MHC molecules which helps to fight off infection by causing more interactions with T-cells3.
            The first section of this article demonstrated that the ability of HLA to create MHC molecules to express pH1N1 is related to the CD8+ T-cell response.  The efficiency score, the ability for a peptide of pH1N1 to be expressed on the cell surface, for 95 common alleles of HLA-A and HLA-B was computed for pH1N11.  Samples from 13 individuals were taken and the participants were ranked according to their average efficiency score for pH1N1.  The samples were then infected with different strains of influenza and the frequency of INF- γ production was correlated with efficiency score1.  Interestingly, age and gender didn’t appear to have any correlation. 

            The second section of the article looked at different alleles and their mortality rates for pH1N1.  95 of the most common HLA class I alleles were studied against many different strains of influenza.  A majority of the alleles demonstrated a preference to bind to pH1N1; however, A*24 alleles didn’t bind well to pH1N1 as seen with their negative efficiency scores1.  This could mean that people with A*24 alleles are more likely to develop severe cases of pH1N1.  Additionally, there was a positive correlation with mortality rate.  Further analysis of the different alleles showed that A*68 and B*39 alleles were also positively correlated with mortality rate while A*32 alleles were negatively associated with mortality rate1.

            The third and final portion of the essay discussed the high rate of HLA-A*24 alleles within native populations.  Even though native people account for only a small percentage of the population, fewer than 5%, they represented almost 18% of all hospitalization cases in Arizona1.  This further supports the claim of this paper: that there is a correlation between HLA allele targeting efficiency and mortality rates. 

            This study indicates that when it comes to H1N1, there are certain alleles for MHC that can be extremely helpful or have little effect when fighting of the flu.  Also, the alleles you have could put you at greater risk for developing a severe case of H1N1.  Hopefully you will avoid the flu this season, and to help you do so keep these tips in mind:

Primary Source:
1. Hertz, Tomer, et al. "HLA Targeting Efficiency Correlates with Human T-cell Response Magnitude and with Mortality from Influenza A Infection." Proceeding of the National Academy of Sciences 110.33 (2013): 13492-3497. Web.

Secondary Sources:
2. "Key Facts About Seasonal Flu Vaccine." Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 25 Sept. 2013. Web. 30 Sept. 2013. < http://www.cdc.gov/flu/protect/keyfacts.htm>

3. Mak, Tak W., and Mary E. Saunders. Primer to the Immune Response: Academic Cell Update. Burlington: Elsevier, 2011. Print.




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