inflammation & autoimmunity

joint & tendon health

CTLA4

An Immune Checkpoint & Its Role in Rheumatoid Arthritis (CTLA4)

Written by Shany Lahan, MS (Neuroscience) on November 18th, 2020

CTLA4 codes for a protein that helps suppress the activity of immune cells. Read more to learn about how variants of CTLA4 may increase the risk of rheumatoid arthritis.

Summary

The CTLA4 gene codes for a protein that suppresses the activity of immune cells. Variants of CTLA4 may play a role in rheumatoid arthritis by decreasing activity or production of CTLA-4. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by increasing CTLA-4 production.

CTLA4 and Rheumatoid Arthritis

Immune cells employ “checkpoints” — proteins that regulate components of the immune system — to prevent inaccurate targeting or excess activation of the immune response [R].

An example of an immune checkpoint is the receptor CTLA-4. When activated, CTLA-4 sends a signal that prevents or stops T cell activity [R, R].

CTLA-4 may be necessary for the development of regulatory T cells (Tregs). Tregs are involved in suppressing the formation of autoantibodies, or antibodies that recognize the body’s own tissues. In this manner, Tregs may function to prevent rheumatoid arthritis and other autoimmune disorders [R, R, R, R].

CTLA-4 is also required to suppress the growth and activity of T cells that release inflammatory proteins [R, R].

Variants of CTLA4 have been associated with rheumatoid arthritis. These variants may lower the activity or production of CTLA-4, which may result in the production of autoantibodies and inflammatory proteins [R, R, R, R, R, R].

Your CTLA4 Results for Rheumatoid Arthritis

SNP Table

variant	genotype	frequency	risk allele
rs3087243
rs11571302

Primary SNP:

CTLA4 rs3087243 [R, R, R, R]

‘G’ = Higher risk of rheumatoid arthritis, relative to ‘A’
‘A’ = Lower risk of rheumatoid arthritis, relative to ‘G’

Other Important SNP:

CTLA4 rs11571302 [R]

‘G’ = Higher risk of rheumatoid arthritis, relative to ‘T’
‘T’ = Lower risk of rheumatoid arthritis, relative to ‘G’

Recommendations

Lifestyle

Sun Exposure (Vitamin D)

The sun is the best source of vitamin D. Multiple studies have demonstrated that vitamin D may increase the production of CTLA-4, as well as promote the development of regulatory immune cells [R, R, R, R].

Vitamin D deficiency is more common in patients with rheumatoid arthritis than in the general population [R].

A study of nurses found that those with greater exposure to UVB rays from the sun had the lowest rates of rheumatoid arthritis. Another study found that people who live further from the equator (who are likely to be exposed to less sunlight on average) are more likely to develop rheumatoid arthritis [R, R].

According to multiple studies, people with a higher intake of vitamin D appear less likely to develop rheumatoid arthritis. However, there are conflicting reports on whether supplementing with vitamin D can improve pain in existing rheumatoid arthritis cases [R, R, R].

The sun is the best source of vitamin D. Vitamin D may help manage rheumatoid arthritis by increasing production of CTLA-4 and promoting the development of regulatory immune cells.

Diet

Increased Omega-3 Intake

Omega-3 fatty acids (including EPA and DHA) were reported to increase the production of CTLA-4 and increase the number of Tregs in multiple mouse studies [R, R].

Interestingly, one study of mice fed an omega-3-rich diet reported a decrease in CTLA-4 — despite observing lower levels of autoantibodies and inflammatory markers [R].

Studies suggest that increased dietary intake of omega-3 fatty acids may protect against rheumatoid arthritis. In a meta-analysis of 20 clinical trials, higher omega-3 consumption improved rheumatoid arthritis symptoms and lab markers [R, R].

Good dietary omega-3 sources include [R]:

Fish and seafood
Flaxseed
Chia seeds
Walnuts
Hemp seeds

Increasing omega-3 intake may help manage rheumatoid arthritis by increasing production of CTLA-4, boosting Tregs, reducing autoantibodies, and decreasing levels of inflammatory markers.

Supplements

Fish Oil

Individuals who don’t get enough omega-3 in their diet may choose to supplement with fish oil. Fish oil may lower the activity of chronic inflammatory and autoimmune diseases, including rheumatoid arthritis [R, R].

A meta-analysis of 17 trials found that supplemental fish oil reduced inflammatory joint pain from rheumatoid arthritis and other inflammatory conditions [R].

In one study of 250 patients, fish oil was as effective as ibuprofen in reducing pain caused by arthritis [R].

Resolvins found in EPA and DHA appear to prevent certain inflammatory proteins from inducing pain [R].

According to a study of immune cells, DHA may increase the production of CTLA-4 [R].

Fish oil may help manage rheumatoid arthritis by increasing CTLA-4 production.

Shany Lahan

MS (Neuroscience)

Shany received her MSc in Neuroscience from Western University.

Prior to joining SelfDecode, Shany conducted research related to Alzheimer’s disease, and taught science to undergraduate students. She believes that research should be accessible to everyone, regardless of scientific background. Shany joined SelfDecode with a mission to help others optimize their health and wellbeing – as well as help them understand the science behind it all.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More inflammation & autoimmunity blogs

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Summary CTLA4 and Rheumatoid Arthritis Your CTLA4 Results for Rheumatoid Arthritis

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