inflammation & autoimmunity

joint & tendon health

CD28

A Gene That Regulates T Cells in Rheumatoid Arthritis (CD28)

Written by Jasmine Foster, BSc, BEd on November 17th, 2020

CD28 encodes a receptor that regulates the growth and activation of T cells. What is its relationship to rheumatoid arthritis? Read on to find out.

Summary

CD28 encodes a receptor that stimulates the growth and activation of T cells. Variants of CD28 may play a role in rheumatoid arthritis by promoting the production of autoantibodies. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by increasing the number of certain types of T cells that express CD28.

CD28 and Rheumatoid Arthritis

The CD28 gene encodes a receptor that stimulates the development and activation of certain types of T cells [R, R].

CD28 is typically activated along with other stimulatory receptors, such as CD40 and TCR. The combined signals of CD28 and other receptors leads to the production of inflammatory cytokines as part of an immune response [R, R].

Variants in the CD28 gene may make the immune system more likely to produce rheumatoid factor, a type of antibody that can attack and destroy the body’s own joint and connective tissues [R].

People who are early in the progression of rheumatoid arthritis tend to produce a higher than normal number of white blood cells that express CD3 and CD8, but not CD28. Rheumatoid arthritis patients also often produce white blood cells that express CD4, but not CD28. CD28 in these combinations may help prevent the production of harmful rheumatoid factor [R, R].

The CD28 receptor stimulates the growth and activation of certain types of T cells. T cells that express combinations of CD receptors, but not CD28, are more common in people with rheumatoid arthritis.

Your CD28 Results for Rheumatoid Arthritis

SNP Table

variant	genotype	frequency	risk allele
rs1980422

CD28 rs1980422 [R, R, R]

‘T’ = Not associated with rheumatoid arthritis
‘C’ = Associated with higher rates of rheumatoid arthritis
The ‘C’ allele may decrease presentation of CD28 on certain T cells, potentially leading to the production of rheumatoid factor antibodies [R, R].

Recommendations

Avoid Cigarettes

In mice exposed to cigarette smoke, T cells expressing CD8 but not CD28 were significantly more common than in mice not exposed. High levels of these T cells are, in turn, associated with rheumatoid arthritis [R, R, R].

Smoking is one of the strongest environmental risk factors for developing rheumatoid arthritis [R, R].

An observational study of 296 people found that 88% of smokers tested positive for rheumatoid factor over a period of 10 years. Also, the rheumatoid factor-positive group of people contained more smokers than the rheumatoid factor-negative group [R].

The risk of high rheumatoid factor levels was 4 times higher in current smokers than in people who never smoked, according to an observational study of 7,124 people. In another study of 100 people with rheumatoid arthritis (RA), rheumatoid factors were more than twice as high in current and former smokers than in people who never smoked [R, R].

Smoking the equivalent of 1 pack (20 cigarettes) a day for 25 years was linked to a 3-fold increase in the risk of elevated rheumatoid factor in a study of 336 RA patients. What’s more, rheumatoid factor levels were directly linked to the number of years smoked in two studies of 673 people with RA [R, R, R].

Exposure to cigarette smoke may promote rheumatoid arthritis by stimulating the growth of T cells that express CD8 but not CD28.

Sunlight & Vitamin D

Vitamin D deficiency is associated with increased numbers of T cells expressing CD8, but not CD28. As previously discussed, this type of T cell is associated with rheumatoid arthritis [R, R, R].

Unsurprisingly, vitamin D deficiency is also 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].

Vitamin D deficiency is associated with both rheumatoid arthritis and higher levels of T cells that express CD8 but not CD28.

Aquatic Exercise

Physical activity appears to regulate CD28 expression on T cells, especially in elderly people. Older patients who exercised had increased numbers of T cells expression CD28 and healthier Th1/Th2 balance compared to those who were sedentary [R, R].

Aquatic exercise, which is most commonly recommended to people with rheumatoid arthritis, describes any type of physical activity that takes place either partially or fully submerged in water. These activities can allow people to maintain physical fitness and reap the benefits of exercise even when they are not fully mobile out of the water [R].

In 2 clinical trials of over 250 people with rheumatoid arthritis comparing the effects of different types of exercise, aquatic exercise produced the greatest pain reduction [R, R].

In the elderly, physical activity increases the number of T cells expressing CD28 and promotes a healthier Th1/Th2 balance. Aquatic exercise is a recommended form of physical activity for people with rheumatoid arthritis.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.

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.

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