Rheumatoid Arthritis: The scientific explanation of the new oral biologic therapies

rheumatoid-handRheumatoid arthritis is a chronic, systemic, autoimmune disease that is driven by inflammatory protein messengers, called cytokines.  Cytokines are produced by cells in the immune system including macrophages, dendritic cells, T cells and B cells. Abnormal regulation of cytokine production leads to the inflammation and tissue destruction that is characteristic of rheumatoid arthritis.

While much attention has been focused on what happens outside immune system cells, more recently, there has been interest in what happens inside these cells that might explain the abnormal regulation of cytokines.

Multiple pathways inside immune cells include pathways with such interesting alphabet soup names like the MAPK pathway, the JAK pathway, the Syk pathway, the NFK pathway, and the PI-3K pathway.

By way of background, if you’ve forgotten your biology, cells consist of an envelope called the cell wall, an inside soup called the cytoplasm, and a core called a nucleus.cell

Cytokines released by immune system cells bind to receptors located on the cell wall.  This binding then sends signals into the cytoplasm of the cell. In the example of the JAK pathway, the receptor on the cell wall, when activated by cytokine binding, sends a signal into the cytoplasm which activates the JAK pathway.

Activated JAKs do something weird then.  They phosphorylate (not an obscene word… just the action of adding a tag) other protein receptors found in the cytoplasm.  These protein receptors act as docking stations for another type of protein called STATs.  Once the STATs dock, they also become activated.  Yes… activation is contagious. These activated STATs then enter the nucleus of the cell and activate genes that lead to the production of more inflammatory cytokines. Pretty complicated, huh?

Why is this important?

It’s because these inflammatory cytokines activate, recruit, and attract more immune cells.  This leads to more inflammation and tissue damage… more or less an endless loop of destruction.

Understanding these mechanisms is what is now driving the pursuit of newer rheumatoid arthritis drugs, called small molecule drugs.  These are oral drugs that have a biologic action.

Clinical trial data has shown these drugs to be effective.  However, like other biologic therapies, they do have potential side effects including elevation of blood pressure, elevation of blood lipids, alterations in blood counts, decrease in kidney function and a few other issues.

Nonetheless, they will prove to be a helpful addition to our arsenal of rheumatoid arthritis treatments.

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