The HLA-B27 gene variant has a strong connection with certain autoimmune disorders. Still, you can carry this variant and maintain flawless health. Read on to learn about HLA genes, the HLA-B27 variant, how it can be detected, and how it relates to autoimmunity. Finally, we share some tips to naturally balance the immune system and reduce inflammation.
We have a more personalized version of this blog post on SelfDecode; check it out here.
The human leukocyte antigen (HLA) system is a group of human genes encoding the major histocompatibility complex (MHC) proteins, or HLAs. This system has three groups or classes; HLA-B genes, along with HLA-A and HLA-C, belong to the class I .
HLAs are proteins or antigens on the surface of white blood cells. They help flag and remove external components that may cause infection. HLA-B antigens bring bacterial or viral proteins from the inside to the cell surface so T-lymphocytes can detect and kill the infected cell .
HLA genes come in many different forms or variants, which enable the fine-tuning of your immune system. Their diversity can be a double-edged sword, however, as some types increase the risk of autoimmune disorders .
The HLA-B27 antigen supports antiviral immune response by “flagging” peptides from viruses – such as influenza, HIV, and Epstein-Barr – and presenting them to T-killer cells .
The most common variations associated with autoimmunity are :
- HLA-B*27:05 (Caucasians/whites)
- HLA-B*27:04 (Chinese)
- HLA-B*27:02 (Mediterranean)
On the other hand, HLA-B*27:06 seems to have a protective role .
The prevalence of HLA-B27 varies from 50% in some Indian populations to almost zero in Australian Aborigines. About 6% of the US population carries this variant, which is more common among white people .
It’s important to note that just because certain genotypes are associated with a disease, it doesn’t necessarily mean that everyone with that genotype will actually develop the disease! Many different factors, including other genetic and environmental factors, can influence the risk of autoimmune diseases.
As mentioned, HLA-B27 strongly correlates with higher rates of certain autoimmune diseases, such as :
- Ankylosing spondylitis (spine deformation)
- IBD (inflammatory bowel disease), in combination with spondylitis
- Reactive arthritis (Reiter’s syndrome) – inflammation of joints, urethra, and eyes
These conditions have a common name spondyloarthritis, the main one being ankylosing spondylitis (AS). In AS, inflammation gradually fuses spine vertebrae, causing back pain and limited movement. It usually affects young men [12, 13].
The connection between HLA-B27 and ankylosing spondylitis (AS) is among the strongest in the HLA system: 90–95% of all AS patients have this variant. For other conditions, the prevalence ranges between 50-90% .
Does this mean almost everyone with HLA-B27 will get AS or another autoimmune disease? Not at all!
Over 50% of people with anterior uveitis (eye inflammation) have this variant, but only 1% of all HLA-B27 carriers develop uveitis .
In other words, HLA-B27 is involved in the above disorders, but many more factors contribute and decide which carriers will get them.
- The way it binds and presents peptides to T-killer cells: upon activation, T-killer cells can mistakenly flag all HLA-B27 fragments as foreign peptides and attack them
- The biochemical properties (structure) of HLA-B27 itself: it can misfold in such a way that causes intracellular inflammation and triggers an immune response
Whatever the root cause, inflammation is the chief mechanism behind these autoimmune disorders .
- Have chronic pain, stiffness, and inflammation in your joints
- Have painful eye inflammation (uveitis)
- The above symptoms began in your early adulthood (the 20s or 30s)
Additionally, your doctor will order HLA tests if you’re undergoing organ or tissue transplantation .
- rs4349859 ( “A” allele correlates with HLA-B27, “G” doesn’t)
- rs13202464 (“G” allele correlates with HLA-B27, “A” doesn’t)
- rs116488202 (“T” allele correlates with HLA-B27, “C” doesn’t)
Carrying two alleles of HLA-B27 (homozygosity) doesn’t correlate more strongly with autoimmune diseases, compared with one allele .
Please note: To confirm the presence of this variant and detect the exact subtype, you may want to do the HLA-B27 blood test.
- Erythrocyte sedimentation rate (ESR) – high value indicates inflammation
- C-reactive protein (inflammation)
- Rheumatoid factor
- TNF-alpha (inflammation)
As mentioned, HLA-B27 is just a link in the chain of factors that can contribute to spondyloarthritis; scientists have discovered other genes and triggers.
We have compiled a list of genetic traits associated with ankylosing spondylitis.
Microbial infections can trigger autoimmune disorders by disturbing the gut probiotics, the guardians of your immunity. Reactive arthritis (previously known as Reiter’s syndrome) is associated with the following infections [44, 45, 46]:
Other factors that may contribute to autoimmune diseases include:
- C-section delivery 
- Antibiotics [50, 51]
- Environmental toxins 
- Sleep deprivation [53, 54]
- Stress 
Please note: none of the approaches listed below are meant to prevent or treat an autoimmune disorder, and they must not be used in place of medical treatment. If you have a diagnosed condition, make sure to consult with your doctor to see if you could add these to your treatment protocol.
Given the role of the microbiome and bacterial infections in autoimmunity triggered by HLA-B27, make sure to boost your gut health by:
- Consuming fermented and other probiotic-rich foods
- Feeding the good bacteria with prebiotics
- Including natural antibiotics in your diet
To keep inflammation in check and balance the immune system, try to:
- Get enough sunlight [64, 65]
- Practice yoga 
- Exercise in moderation [67, 68]
- Get enough sleep [69, 70, 71]
- Try cryotherapy [72, 73, 74]
The following supplements may help by supporting your immune system and reducing inflammation:
- Vitamin D (not a substitute for sunlight) [75, 76]
- Probiotics (Lactobacillus GG) [77, 78]
- Turmeric [79, 80, 79]
- CBD oil [81, 82]
- Omega-3/fish oil 
- Green tea (EGCG) [84, 85]
- Quercetin [86, 87, 88]
- Thunder god vine [89, 90]
Food irritants can have an important role in inflammation and autoimmune disorders. The Lectin Avoidance Diet has a powerful program to help you detect and eliminate foods that are pro-inflammatory for you (hint: it’s not just about lectins).