Lupus Now Research Update Issue #6

Protein May Regulate How Cells in the Body Grow or Self-Destruct
Espinosa, A.; Zhou, W.;  Ek, M.; et. al. Journal of Immunology 2006; 176: 6277-6285

Individuals affected by Sjögren’s syndrome and lupus have immune system proteins (autoantibodies) that target a protein called Ro52. They also make unusually high amounts of Ro52. However what the purpose of this protein is in the body, or why the immune system is zeroing in on it in these patients, is not yet understood. The researchers wanted to study what effect on the immune system having extra Ro52 might have.

Using B cells from a mouse model of lupus, the researchers manipulated these cells to make excessive amounts of Ro52 to see how this would affect the cell. They found that if you give these cells with extra Ro52 protein triggering signals, which usually cause cell activation and death (the CD40 signaling pathway), this caused decreased cell growth and increased cell death over what would otherwise be expected. Next, when they then reduced the amount of Ro52 made by these cells, it restored the ability of the cells to live longer.

The findings suggest the possibility that increased manufacture of Ro52 by patients with Sjögren’s and lupus could be part of the reason why they have unbalanced immune cell activation and problems with regulated immune cell disposal (programmed cell death or apoptosis).  The killing-off and disposal of expired immune cells needs to proceed in an orderly manner in order to prevent further inflammation in the bloodstream. This might contribute to the dysregulation of the immune system in people with Sjögren’s syndrome and lupus.  Click here to read the complete abstract.

Simpler Measures for Predicting Kidney Function May Be Useful

Leung, Y.Y.; Lo, K.M.; Tam, L.S.; et. al.., Lupus Vol. 15, No. 5, May 2006, pp. 276-281

In order to measure how well the kidneys are functioning, doctors frequently use a measurement called the creatinine clearance (CrCl). Creatinine is a breakdown product of creatine, a component of muscles in the body. The way that the kidney eliminates creatinine reflects how well the kidneys are working.

The CrCl test compares the level of creatinine in the urine with the creatinine level in the blood. The classic way of doing this takes measurements on a sample of urine that has been collected over a 24-hour period, and compares this to a blood sample drawn at the end of that time. Because creatinine is freely filtered through a well-functioning kidney and not reabsorbed into the bloodstream the way some other proteins are, creatinine clearance can be used to estimate how fast the kidney is filtering out wastes from the body (known as the glomerular  filtration rate (or GFR). This is the gold standard by which kidney function is assessed. As kidneys become damaged, the GFR goes down and less creatinine is filtered out, leaving more creatinine in the bloodstream, along with other potentially toxic waste products.

Researchers wanted to know whether creatinine clearance (CrCl) that is estimated by different, easier methods agreed with the CrCl measured, using a 24-hour collection of urine. Forty-three lupus patients with mild to moderate kidney disease were studied. For this study, the methods used to estimated creatinine clearances were (1) the Cockcroft-Gault (CG) equation, (2) the Modification of Diet in Renal Disease (MDRD) study equation, and (3) the abbreviated MDRD (aMDRD) study equation. These methods each were compared to the measured CrCl by 24-hour urine collection.

The results were that the MDRD and aMDRD methods seemed more accurate than the CG equation. However, there seemed to be a tendency for the MDRD and aMDRD study equations to underestimate CrCl, making the kidneys appear to be functioning more poorly that was indicated using the 24-hour urine collection data. Some, however, would argue that there are some inaccuracies in all of the methods, including the 24-hour urine collection. The take-home message from these studies is that easier methods for measuring kidney function, although not perfect, are reasonably reliable. They certainly can be used and understood in evaluating how patients with kidney disease are doing and in examining the progress over time of people undergoing treatments. This could be of significant benefit in treating patients and also in running clinical trials of new medications.  Click here to read the complete abstract.