June 23, 2017
According to Pub Med, the repository of all medical articles written in the peer review literature, there were 3540 articles published on lupus in 2016 in recognized medical journals. Although they covered a variety of topics, this column focuses on three that this writer believes to be of particular interest.
Kidney structure consists of the glomerulus which performs the filtering function of the kidney and is connected to tubules, or small canals which transport waste to the ureter, and ultimately the bladder for excretion. For over 50 years, doctors have associated inflammation of the glomerulus with lupus and identified tissue types under the microscope that are associated with disease activity and outcomes. Recently, it has been shown that the tubulointerstium, or tubules and the tissue around them, are more important and may be the location of tissue inflammation. Nephrologists and rheumatologists are now looking at markers of this, which over the next 5 years, will totally change the way we treat lupus kidney disease.
The human kinome controls much of intracellular cell signaling that directs how proteins and their enzymes signal how a cell behaves. There are over 500 kinases in our kinome. Until recently, lupus researchers paid little attention to this. There are several families of kinases that influence inflammation. These have names such as Syk, BTK, JAK and tyrosine kinase inhibitors. The first drug to block JAK was introduces two years ago to manage rheumatoid arthritis and is known as tofacitinib (Xeljanz). Improvements in our knowledge of kinome biochemistry have been rapid, and no fewer than 10 such molecules are being studied in lupus clinical trials.
If a woman with SLE has an identical twin sister, the chances that her twin will also develop lupus is 25%. This suggests that environmental factors and hormonal factors account for the majority of lupus. Recent studies have suggested that tobacco smoke, pollution, ultraviolet light from the sun, and especially dietary factors play a role. The bacterial makeup of our gut, known as the microbiome, differs from person to person. Recent work suggests that a part of the epigenome, whereby heritable or acquired modifiers of DNA without any change in the DNA base sequence can alter immune function. This includes a process known as methylation. Hypomethylated diets may flare lupus in certain mouse strains. Also, recent work has suggested why more women develop SLE. It appears that the X sex chromosome (females are XX and males are XY) in combination with T cells might upregulate the immune response. In other words, non-genetic factors may promote and flare lupus.
This is an exciting time in lupus research and the with your support, further advances will be made.
Daniel J Wallace MD