This study in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE) will explore whether the alteration of a gene that is involved in antibody formation is implicated in the disease.
Autoimmune diseases like SLE are cases of mistaken identity. Immune system antibodies, made by immune B cells, are part of the body's second line of defense. They learn to recognize a specific foreign invader and attack it whenever it appears. Occasionally, however, antibodies mistakenly identify the body's own tissues as foreign and attack them. In SLE, these errant "autoantibodies" attack several organ systems, causing them to malfunction.
The Alabama researchers recently demonstrated that SLE patients often have alterations in a specific gene, called the VH gene, which is involved in the development of immune B cells. The investigators hypothesize that an abnormal replacement of a section of this gene may cause B cells to create autoantibodies that attack DNA in various body organs, resulting in SLE.
The researchers suspect that this gene alteration occurs as B cells mature in the bone marrow. Alternatively, the error could occur once B cells mature and leave the bone marrow to circulate in the patients' blood. To determine what occurs, the investigators will pursue three steps. First, they will find out whether VH gene alterations are correlated with the disease, by collecting blood from SLE patients and healthy controls and seeing whether only the patients have the altered VH gene in their immune B cells. Next, the investigators will determine whether the patients' immune B cells, containing the altered gene, produce antibodies that react to the patients' own DNA. Thereafter, the researchers will determine whether the gene's alteration occurs in the patients' B cells while these cells are developing in bone marrow or after they have entered the bloodstream. The answers may help to explain how autoimmunity occurs in SLE, and perhaps in other autoimmune diseases as well.