Complement Complications

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Classical Complement System

Hey y’all! Today we’re going to get into the complement system and how it works. What’s even more interesting, is eventually we’ll look at what can happen in the body if it’s not working properly, so buckle up! First off, we need to take a look at what exactly the classical complement pathway is and how it works. This will lay the groundwork and let us know exactly how errors can affect us. Furthermore, it will help explain why we see the effects that we do when something goes wrong.

The complement system is broken down into four main functions: opsonization, inflammation, chemoattractions for PMNs, and lysis. This Nature article outlines the complement system well and covers these topics. Opsonization is initiated by C3b which tags them for phagocytosis. The key molecules for inflammation are C3a and C5a. Chemoattractions for PMNs are modulated by C5a which helps recruit the PMNs to the site of infection. Lysis occurs through C5a and C9 which form the membrane attack complex (MAC). This pathway is most useful for fighting extracellular bacterial infections.

The Complication

Next we’re going to take a look at how problems with the complement system can cause health issues. Specifically, we’ll be investigating Lupus erythematosus. This Nature article dives into what Lupus is and how it occurs. Lupus is an autoimmune disease that involves a loss of tolerance to self antigens. Women are much more susceptible to Lupus than men are and some racial disparities are found as well.

This Nature article specifically discusses the autoantibodies that typically contribute to Lupus. Specifically, antinuclear antibodies are very characteristic in Lupus. These antibodies target nucleic acids in the body. There are also anti-Smith antibodies that target the spliceosome. Additionally, looking at this PubMed article, a typical biomarker of Lupus is issues with the kidneys. Furthermore, these complications can be life-threatening and often fatal if not managed well.

The Pathway

Now we can see how the complement system specifically is involved with Lupus. This article on Frontiers, goes into how Lupus is characterized by low levels of C3 and C4 in the complement system. This deficiency has been linked to development of Lupus and is a common precursor. Furthermore, this PubMed article discusses how C3b exacerbates the condition through opsonization. The complement system activates flares in Lupus and can tend to target the kidneys as we discussed earlier.

Finally, despite all these issues, researchers are on a road to finding a treatment for Lupus. While no explicit complement system treatments designated for Lupus exist, there are promising studies. For example, this PubMed article goes into a treatment that blocks central complement activation. While there are no true treatment plans for Lupus developed yet, it shows promise as a potential treatment. The trials are currently in phase II and more research needs to be done… bummer. But, the research for complement treatments for Lupus are promising! There are many other avenues being explored and soon we might find something that is incredibly effective!