inflammation & autoimmunity

ICAM3

Connecting Cytokines & White Blood Cell Activity in Lupus (ICAM3)

Written by Jasmine Foster, BSc, BEd on December 1st, 2020

The ICAM3 gene influences the activity of white blood cells and the production of cytokines. What is its link to lupus? Read on to learn more.

Summary

ICAM3 encodes intercellular adhesion molecule 3. Variants of ICAM3 may play a role in lupus by increasing white blood cell activity and cytokine production. Lifestyle, diet, and supplement modifications may counteract the effects of these variants by suppressing certain cytokines.

ICAM3 and Lupus

The ICAM3 gene encodes an intercellular adhesion molecule (ICAM) that helps white blood cells stick to other tissues and move around the body. Researchers believe that, in addition to helping white blood cells move, ICAM3 sends important signals during an inflammatory immune response. It has also been implicated in inflammatory signalling in cancer, and it helps clear dead white blood cells from the body [R, R, R].

Multiple ICAM3 variants have been associated with autoimmune diseases like rheumatoid arthritis and lupus [R, R].

Variants in ICAM3 may also affect the expression of the TYK2 gene. TYK2 encodes tyrosine kinase 2, a member of the JAK protein family. Members of the JAK family activate STAT (‘Signal transducer and activator of transcription’) proteins in response to cytokines [R, R].

TYK2 is believed to play a role in the antiviral immune response through the interferon pathways. Mutations that interfere with the function of TYK2 have been associated with immune deficiency [R].

Other variants, however, may be protective against autoimmune diseases [R, R, R, R].

ICAM3 helps white blood cells move around the body and may send inflammatory signals during an immune response. Variants in the ICAM3 and neighboring TYK2 genes are associated with lupus.

Your ICAM3 Results for Lupus

SNP Table

variant	genotype	frequency	risk allele
rs34536443
rs2304256
rs35251378

ICAM3 rs34536443 [R, R]

‘G’ = Associated with relatively higher rates of lupus
‘C’ = Associated with relatively lower rates of lupus
The ‘C’ allele may reduce the activity of TYK2 and ICAM3 and suppress the production of inflammatory cytokines [R, R].

ICAM3 rs2304256 [R, R]

‘C’ = Associated with relatively higher rates of lupus
‘A’ = Associated with relatively lower rates of lupus
The ‘A’ allele may reduce the activity of TYK2 and ICAM3 and suppress the production of inflammatory cytokines [R, R].

ICAM3 rs35251378 [R]

‘G’ = Associated with relatively higher rates of lupus
‘A’ = Associated with relatively lower rates of lupus
The ‘A’ allele may reduce the activity of TYK2 and ICAM3 and suppress the production of inflammatory cytokines [R, R].

Recommendations

Vitamin D

Vitamin D supplementation lowered IL-12 levels in some human studies but not in others. In a study on 57 people with lupus, vitamin D deficiency was associated with increased IL-23 levels. Both IL-12 and IL-23 signals rely on TYK2 [R, R, R, R, R].

People suffering from lupus have lower vitamin D levels and are at a higher risk of deficiency than healthy people according to several meta-analyses involving over 4,000 people [R, R, R, R].

Controlled trials of 490 lupus patients found that supplementation with vitamin D increases the blood levels of this vitamin and may reduce fatigue, but has no effect on lupus severity [R].

Note: sunlight exposure is usually recommended as the best way to get sufficient vitamin D, but many people with lupus are hypersensitive to UV radiation and develop skin damage in response to sunlight [R].

Using highly protective, broad-spectrum sunscreens prevented injuries caused by UV radiation in 3 controlled clinical trials (one of them placebo-controlled) on 56 people with lupus. People with lupus are advised to use sun protection every time they go out [R, R, R].

People with detrimental ICAM3/TYK2 variants may be more susceptible to vitamin D deficiency. To safely get sufficient vitamin D, consider supplementation and wearing appropriate protection when you go out into the sun.

Omega-3 Fatty Acids

Omega-3 fatty acids found in fatty fish, EPA and DHA, may inhibit Th17 cells and lower the levels of IL-17 and IL-23. IL-23 signalling, in turn, relies on TYK2 [R, R, R].

Omega-3 fats can also inhibit STAT3, a downstream target of the JAK enzymes [R].

In 6 clinical trials (most of them placebo-controlled) of 230 people with lupus, supplementation with 3-20 g/day omega-3 fatty acids for up to 6 months improved the symptoms, fatigue, quality of life, blood vessel function, blood fat profile, inflammatory markers and oxidative stress [R, R, R, R, R, R].

However, the results are mixed: omega-3 fatty acids were ineffective at improving lupus severity and kidney damage in 4 placebo-controlled trials on 181 people [R, R, R, R].

The richest supplemental source of omega-3 fatty acids is fish oil.

Omega-3 fatty acids may help balance the expression of cytokines associated with TYK2. Some studies suggest that omega-3 supplementation could help improve lupus symptoms.

Thunder God Vine

Celastrol, an active compound of thunder god vine (Tripterygium wilfordii), may reduce the production of inflammatory cytokines including IL-12 and IL-23, which rely on TYK2 [R, R].

Thunder god vine improved several cases of lupus in China. Most of the studies (a combination of case studies and non-placebo controlled trials) that support its use date back to the 80s, leaving this benefit uncertain [R, R, R, R, R, R, R].

In mice with lupus, thunder god vine increased survival and reduced kidney damage and inflammation [R, R, R, R, R, R, R].

Celastrol from thunder god vine may help regulate TYK2-associated cytokines and improved lupus symptoms in some studies.

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.

More inflammation & autoimmunity blogs

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