HLA-B27: Genetic Variants That Increase Susceptibility to Autoimmune Diseases

Our immune system does an awesome job, most of the time, at fighting off pathogenic bacteria and viruses. But to fight off these pathogens, the body needs to know that they are the bad guys.  One part of our immune system is the major histocompatibility complex, also known as HLA, or human leukocyte antigens. The HLA genes produce proteins that, as part of our innate immune system, help our body determine what is a foreign invader that needs to be attacked.

There are many different HLA serotypes that people can have, giving us all slightly different strengths and weaknesses against microbial diseases. But along with attacking foreign invaders, a handful of HLA types also increase the susceptibility to autoimmune diseases, where the body attacks its own cells.

HLA-B27 is linked to susceptibility to inflammatory related autoimmune diseases including ankylosing spondylitis[ref], reactive arthritis, psoriasis, and inflammatory bowel disease.[ref]

Ankylosing spondylitis is a chronic inflammatory disease that mainly affects the spine.  It causes back pain and spinal stiffness, and the vertebrae can fuse together. More info can be found on the Spondylitis Association of America site.


Genetic variants included in 23andMe data that are associated with HLA-B27 are listed below.  Note that these genetic variants are not completely predictive of the HLA-B27 serotype.  These variants show if you are likely or not to carry an HLA-B27 type, but there are several subtypes of HLA-B27 and not all of them cause the higher risk of inflammatory autoimmune diseases.  A blood test is still necessary to be 100% certain that you carry the HLA-B27 type associated with autoimmune diseases.

Check your 23andMe results for rs4349859  (v5 only):

  • AA: high likelihood of carrying 2 copies of HLA-B27[ref][ref][ref]
  • AG: high likelihood of carrying 1 copy of HLA-B27
  • GG: normal

Check your 23andMe results for rs13202464 (v4, v5):

  • GG: high likelihood of carrying 2 copies of HLA-B27[ref][ref][ref]
  • AG: high likelihood of carrying 1 copy of HLA-B27
  • AA: normal

Don’t freak out if you are a carrier of HLA-B27 — certain populations have up to 20% of people carrying these variants. In Caucasians, about 10% of people carry one copy, whereas only 1% of Africans carry HLA-B27.[ref]

Although HLA-B27 dramatically increases the risk of ankylosing spondylosis over the risk that someone without this HLA type would have, ankylosing spondylosis is rare with about 1 in 2000 people having it.[ref] If you have the HLA-B27 serotype, the lifetime absolute risk is about 6%.[ref]  There are other genetic variants thought to be involved in the risk for ankylosing spondylosis,  as well environmental factors.[ref]

Interestingly, carriers of the HLA-B27 have a survival advantage for HIV and hepatitis C.[ref]

There is also a connection between HLA-B27 and changes to the gut microbiome.[ref] Spondylitis patients also showed changes in the gut microbiome with decreased F. prausnitzii and increased Bacteroides fragilis.[ref]

If you carry the HLA-B27 type and also have reactive arthritis, there is an interesting tie to salmonella persistence or other microbial infections.

Animal studies show that Lactobacillus GG probiotics may help with preventing recurrence of inflammatory bowel problems associated with HLA-B27.[ref]  Although I couldn’t find a human clinical trial on it, if you are wanting to try a Lactobacillus GG probiotic, Culturelle contains that strain.

The link between diet and symptoms of reactive arthritis or ankylosing spondylitis isn’t clear.  A meta-study looked at a bunch of studies on the subject and found no statistical links with diet. But individuals report that diet can make a difference in their joint pain with certain foods making it worse.  So trying an elimination diet or the autoimmune protocol diet may be worthwhile.

 

 

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