With the basic and historical understanding of SLE, it is established that there are multiple causes of this disease and affect patients differently. It is understood that patients carry genetic factors that increase the likelihood of lupus emerging; however, there is a strong link between environmental factors or these “triggering” factors that start the onset of this disease. It is important to note that some of the strongest genetic links to SLE are from the complement system C1Q and C4 single-gene defects. Also, patients genetically have been found to have several genes mutated, including interferon regulatory factor 5 (IRF5) which could increase the levels of the type 1 IFN family. While these genetic factors are important and can indicate a strong chance of a patient developing lupus, environmental triggers like UV light exposure, Epstein-Barr virus infection and other factors help create cell damage that promote this inflammatory response against cells. This is particularly what makes lupus so interesting yet so complex and challenging, in that there is not one single way for a person to develop disease but there are general trends for how this disease onset occurs. While there isn’t one particular infectious agent that causes lupus, a good example on how a virus can trigger the disease is Epstein-Barr virus or EBV. EBV has a protein called EBNA2 that binds to human transcription factors and “turn on genes associated with an increased risk of lupus,” like triggering the mutations of TLR signals. This virus also causes catastrophic cell and DNA damage on the host, which can alter how the hosts immune system reacts and how B cells function in response to the disease leading to eventual chronic immune overactivity and autoimmune disorders. Interestingly enough, there are seven autoimmune disorders including lupus, RA and MS that share a common set of abnormal transcription factors that can be altered and impacted by viruses like EBV. So from the lens of a nonscientist, lupus is caused by both environmental and genetic links that when combined together at the ideal time can cause irreparable damage to the patient and cause this chronic inflammation as seen in SLE.
Curiouser and Curiouser: The science behind the madness
