ALCAM in Lupus
Lupus nephritis (kidney disease) is one of the most serious complications of lupus. With the TIL grant support, Dr. Mohan will build on his existing discoveries to evaluate a potential new therapeutic target for lupus nephritis. In comparing the levels of 1,100 proteins in the urine of lupus patients and healthy controls, Dr. Mohan already found several differences, and one in particular stood out. The protein ALCAM (activated leukocyte cell adhesion molecule) was consistently higher in those with lupus compared to the controls. ALCAM is a small molecule on the outside of T cells of the immune system that helps the T cells move through the tissues of the body, including the kidney.
What this study means to people with lupus:
Dr. Mohan will find out how ALCAM is involved in lupus nephritis and evaluate whether it is a good target for new drug development to prevent or treat the complication.
When we interrogated the levels of 1100 different proteins using an aptamer library, urine samples from patients with lupus nephritis exhibited elevations in a couple of different proteins compared to urine from control subjects. Among the elevated urinary proteins, one molecule that was consistently validated to be elevated in multiple patient cohorts was Activated Leukocyte Cell Adhesion Molecule (ALCAM or CD166), an activation molecule on lymphocytes that is important for adhesion and cell migration. Preliminary studies reveal ALCAM to be elevated on lymphocytes within the kidneys in murine and human lupus nephritis. This proposal is designed to evaluate the candidacy of ALCAM as a therapeutic target in lupus, and its biology in disease pathogenesis. In the first Aim, we will define the expression profile of this molecule in a murine model of lupus. In the second Aim, we will evaluate if the development of lupus nephritis is contingent upon the presence of ALCAM, using pharmacological and genetic approaches. In the final Aim, we will carry out translational studies in human SLE and lupus nephritis.