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OK, I have rheumatoid arthritis and I've been injecting Humira 2 times a month for the last 8 months.

As far as I know rheumatoid arthritis is simply an immune system disorder which makes the immune system produce more proteins called Tumor Necrosis Factor alpha which regulate body disorders. When I inject Humira I actually import a protein called Adalimumab which is a TNFα inhibitor.

So far so good but my question is

Does my body throw this protein away after some time? How is this protein removed from my body?

What about the way Adalimumab inhibits TNF, does it bind to TNF?

Also the details of how rheumatoid arthritis appears are not well known but the main reason is because of the patients DNA isn't it?

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2 Answers 2

Adalimumab is an antibody that binds to tumor necrosis factor alpha. Antibodies have high-affinity binding sites for their antigen, and for a small antigen such as TNF-alpha, would bind to it and prevent it from binding to its target receptors. Antibodies, like all proteins, degrade after a certain period of time and are removed from circulation, and since the body does not produce more of this antibody, it must be re-administered every few weeks.

The mechanism of this pharmacological is in a sense somewhat ironic in that in nature the chief role of antibodies is binding and neutralization of foreign and potentially dangerous antigens, however, this antibody binds and neutralizes a feature of the immune system itself. This element of the immune system is a cytokine, TNF-alpha, whose function is to promote inflammation, which draws white blood cells to the site of the inflammation and activates them. TNF-alpha also induces fever, and suppresses tumor formation and viral replication by activating programmed cell death pathways.

Aggressive immune responses always cause collateral damage to surrounding tissues, however, in autoimmune diseases such as rheumatoid arthritis the damage is compounded by the fact that the target of the immune response is an element of the body itself. A central function of the immune system is to induce tolerance to self; sometimes tolerance fails and while there are genetic components involved, the process is yet to be well-understood.

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Prufrock +1 for the answer ! It would be helpful if you could include a source for this. –  biogirl Oct 23 '13 at 9:24
    
i still dont know how exactly this antibodies degrade after a certain period of time . As far as i know things in our world dont just disapear they just transform to other things. –  Flux Oct 23 '13 at 18:19
    
Recall that antibodies are proteins, and proteins are composed of smaller molecules known as amino acids. Proteins are extraordinarily elaborate entities, but as all things become damaged over time and no longer function. The antibodies eventually break in a literal sense, and the cells of the blood decompose them back into amino acids to be made into new proteins. The matter in the body is not static but is constantly being reorganized. –  J. Alfred Prufrock Oct 25 '13 at 23:20
    
@biogirl - Although not a great general source, Wikipedia gives most of this information regarding Adalimumab. One of the original pharmacokenetic studies of this drug is described by Weisman et al. in the journal Clin Ther. 2003 Jun;25(6):1700-21. In PubMed there is also a review by Bang and Keating in BioDrugs. 2004;18(2):121-39, but I do not believe it is freely available. It is likely there are other reviews of Adalimumab that are freely available. –  J. Alfred Prufrock Oct 25 '13 at 23:37

Afaik. RA and psoriasis are probably caused by a malfunction of genes which regulate IL-23 production. IL-23 is required for Th17 cells to survive. Th17 cells produce a lot of things which result in inflammation and since TNF-α is a key mediator in inflammation and break down of joints, reducing the amount of available TNF-α reduces the inflammation.

(Th17 cells produce IL-17, IL-21, IL-22, IL-6 and TNF-α. Th17 cells are playing against Treg cells, which try to protect self cells. IL-17 promote osteoclastogenesis, and osteoclasts break down bone. According to serveral wikipedia articles IL-17 induces the production of other cytokines such as IL-6, IL-1β, TNF-α. IL-21 is required for sustained CD8+ T cell effector activity. IL-22 is a mediator of cellular inflammatory responses. IL-6 modulates the resistance of T cells against apoptosis, induces activation of T helper cells and promotes osteoclastogenesis. TNF-α is an endogenous pyrogen which is able to induce fever, apoptotic cell death, cachexia, inflammation and inhibits tumorigenesis and viral replication. IL-1β is a mediator of the inflammatory response, and it is involved in the regulation of apoptosis as well.)

Adalimumab is an immunoglobulin, which binds to TNF-α, and so it prevents it to bind TNF-α receptors and cause inflammation. After it is bound to its target you cannot reuse it, that's why you need daily doses of it. It is degraded by liver and kidney cells, or probably by phagocytes as well.

There are other TNF-α blocking pharmaceuticals as well. There are IL-23 inhibitors, one of them is called ustekinumab. It is an immunoglobulin too and it is used by treating psoriasis. By RA it is currently under clinical trial, but I guess it will work by RA as well. There is an IL-23 inhibitor which is not an immunoglobulin and can be taken orally, it is called apilimod. Sadly it failed the clinical trials, it had only mild effect. It probably does not reach the inflammation in sufficient amount. Maybe later there will be an effective delivery method and so a drug which can be taken orally.

There are alternative natural therapies: TNF-α inhibitors which you can take orally, for example γ-linolenic acid, ω−3 fatty acids, chondroitin sulfate, etc... These can be useful by mild cases of RA. Probably fever therapy works by mild cases as well. Afaik. cryotherapy has nice results in treating RA and its positive effect lasts much longer than the effects of any drugs, so if you aren't afraid of cold, that is a nice alternative therapy as well.

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