Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which immune cells mistakenly identify the body's own cells as "foreign" and attack them. It produces damage intermittently (an "on-again, off-again" course), affecting multiple organs including the skin, kidneys, and central nervous system. About 25 percent of patients are children; many of them suffer from kidney failure. Lacking an understanding of the specific cause(s), current treatment consists of generalized use of anti-inflammatory and immuno-supressive drugs. This treatment carries many side effects, especially in children.
Baylor Institute scientists' research on the cause of SLE, however, may lead to a better understanding of this and perhaps other autoimmune diseases and to highly targeted therapy. The researchers' recent studies suggest that SLE may be caused by alterations in dendritic cells. These are immune cells that normally recognize a "foreign" invading antigen, and display the antigen's molecular structure to immune T and B cells, which then find and attack the antigen.
When dendritic cells misidentify the patient's own cells as "foreign" and direct T and B cells to attack, however, an autoimmune response occurs. The scientists previously found that pediatric SLE patients have an over-expression of interferon, an immune substance that can prompt immature (undifferentiated) cells in patients' blood to develop several features of dendritic cells.
Using a new approach, termed "global gene expression analysis," to determine which genes are expressed at higher levels in blood cells taken from patients with SLE, Dr. Pascual has found that the overrepresented genes were of two classes: genes that are turned on in response to interferon, and genes that are expressed by young or immature white blood cells called granulocytes.
The researchers hypothesize that the immature granulocytes are contributing to the disease. One of their hypotheses is that the granulocytes are captured by the interferon-activated dendritic cells and serve as "self" antigens that drive the autoimmune attacks in SLE. They will explore this hypothesis by characterizing the undifferentiated (immature) granulocytes, establishing whether these cells infiltrate the skin, kidney and nervous system, and determining whether these cells are responsible for the organ tissue destruction characteristic of SLE. If so, therapies that can control interferon or the immature granulocytes might provide new and highly targeted treatments.