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TLR 7 agonist has been linked with development of autoimmune disease, namely lupus like disease. The question is, why does it happen?

I think a mechanism of why it happens would also reveal answers to questions like- Can a real virus also trigger such adverse effects?

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There is a subtype of lupus called Drug induced lupus (DIL), as the name says certain drugs cause the signs and symptoms of lupus in susceptible individuals. The difference between DIL and normal lupus (SLE) is that the signs and symptoms disappear in drug induced lupus after drug cessation.

The mechanism of drug induced lupus (also normal SLE) is complicated and involves genetic susceptibility, adaptive immunity and innate immunity in which TLR-7 is involved. For example the two most common drugs that cause DIL are procainamide (anti arrhythmic) and hydralazine (anti hypertensive) and the mechanism by which they cause DIL is inhibition of DNA methylation which leads to hyperactive CD4+ immune cell, as you can see here TLR-7 has no role as CD4+ is part of adaptive immunity. (https://www.ncbi.nlm.nih.gov/books/NBK441889/). For toll-like receptors role in lupus you can read this article https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-018-0436-2

I am not sure about the involvement of TLRs in lupus in case of virus infection. Toll like receptors are involved in viruses' recognition but if the mechanism is similar to that of drug induced lupus then theoretically the signs of lupus should disappear when the infection is terminated.

The role of viruses and bacteria and other environment substances in autoimmune diseases in susceptible patients is based on several theories and of these theories is cross-reactivity; the theory says that foreign bodies act as "triggers" for the autoimmune diseases, the idea is that certain amino acids sequence in the virus will be similar to certain amino acids in different tissue in the body and the immune system will start to attack these tissues thinking they are foreign to the body. This is the mechanism by which Post-streptococcal glomerulonephritis, IgA nephropathy, rheumatic fever, etc... are induced. (https://adc.bmj.com/content/79/5/448).

In this article you can see the CMV virus is found to cause lupus through cross reactivity (https://www.nature.com/articles/s41598-020-66804-1) perhaps it will be useful in explaining the role of viruses in lupus.

This article is useful in explaining different mechanisms of autoimmune diseases: https://www.britannica.com/science/immune-system-disorder/Autoimmune-diseases-of-the-thyroid-gland

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  • Thanks for the answer. You wrote- "The difference between DIL and normal lupus (SLE) is that the signs and symptoms disappear in drug induced lupus after drug cessation." Does this mean that if someone takes a vaccine containing TLR7 agonist and some weeks/months pass with them not experiencing any major adverse effects, then conditions for them is not going to deteriorate after that. That is, their likelihood of developing lupus at a later stage is not going to increase because of the exposure through the vaccine? Dec 14, 2021 at 17:04

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