Consortium researchers will study whether autoimmune lupus is associated with a genetically determined failure to regulate certain immune cells and whether this condition is more prevalent in African-Americans than other population groups.
Lupus is an inflammatory autoimmune disease affecting organs, joints, skin, and the brain. Immune cells mistake components of the body's cells as foreign and attack them. Initial studies of lupus patients' cells suggest that a certain receptor on immune B cells fails to curtail errant B-cell attacks on the body's tissues. Since this receptor ("FcRIIB") is also located on dendritic cells, which summon immune B cells to attack, regulatory dysfunction of dendritic cells also may contribute to the disease.
In previous studies, B cells in 30 of 60 lupus patients were found to have low receptor levels when the B cells were developing the capacity to attack. This situation occurred disproportionately in African-American study participants. In immune cells from a more ethnically diverse patient group, investigators will study this receptor throughout B cell development, and look for alterations in the gene that directs the receptor's production. Researchers will see whether low receptor levels produce, or are a consequence of, dysfunctional dendritic and B cell regulation, in cells of lupus patients receiving "autologous" (own body) stem cell transplantation. They then will try to increase receptors in stem cells that give rise to these immune cells, as a potential therapy.
Significance: A finding that genetically determined low receptor levels facilitate immune B cell attacks in lupus would spur potential genetic or stem cell therapy studies.