Gabor Illei, MD, PhD, MHS, Head, Sjögren’s Syndrome Clinic, Gene Therapy and Therapeutics Branch, NIDCR:

Combined NIDCR/NIAMS Fellowship in Women’s Health

Systemic lupus erythematosus (SLE) and Sjögren’s Syndrome are systemic autoimmune diseases affecting primarily women with 90% of patients being females. SLE and SS share many clinical and pathogenetic characteristics. They may present independently but they can also co-exist and about 30% of SLE patients fulfill criteria for SS.

Similar pathogenetic mechanisms are suggested by the presence of shared autoantibodies, such as anti-SSa and anti-SSb, and the recently described type-1 interferon gene expression signature observed in both diseases. There are also many clinical manifestations that are shared between SLE and SS, such as fatigue, unexplained cognitive dysfunction, leukocytoclastic vasculitis, peripheral neuropathies and arthritis.

We propose a combined NIDCR/NIAMS fellowship position under the supervision of Gabor Illei, Head of the Sjögren’s Syndrome Clinic, NIDCR. The goal of the fellowship would be to combine clinical research efforts in areas that are common to SLE and SS, by drawing on the strength of multiple specialties. Depending on the candidate’s interest, he/she could choose from various clinical projects. These would address areas that are common in both diseases or that require an interaction of rheumatologists, oral medicine experts and other subspecialties.

Specific projects may include:

1. The association of the increased risk of premature atherosclerosis in SLE with periodontal disease (PD). Several recent studies demonstrated a very significant increase of premature atherosclerosis in SLE with a 40-fold increase in young women in one study. In fact, the major cause of mortality in SLE is cardiovascular disease. On the other side, a subset of periodontal disease has also been linked to atherosclerosis in the general population. This study would evaluate the potential contribution of PD to the increased risk of atherosclerosis in SLE patients by combining a careful clinical and molecular analysis of PD with assessment of atherosclerosis and SLE. If any association is found, future studies are planned to address the impact of treating PD on atherosclerosis in this population.
2. Cognitive dysfunction. In SLE 40-60% of patients have some degree of cognitive dysfunction of unclear etiology in most cases. Cognitive dysfunction is also common in SS, but the extent of it is less well characterized. This project will be the extension of a study of cognitive dysfunction that was recently completed at the NIH in lupus patients with the possibility of doing a pilot treatment study of cognitive dysfunction in SS and SLE with drugs that have shown some benefit in slowing cognitive deficits in patients with Alzheimer disease.
3. Fatigue Fatigue is one of the most common complaints in both SLE and SS and in most cases is not explained by the conventional measures of disease activity. Careful evaluation of immunologic and neuroendocrine factors using multiplex technologies could be done in short-term clinical studies using Provigil, an agent that has shown short-term benefit in fatigue associated with multiple sclerosis.
4. Immunomodulatory therapies There are several novel biologic agents that could be evaluated in small pilot studies in both SS and SLE. Given the clinical and pathogenetic similarities between the two diseases, running studies in parallel will significantly increase the amount of information we may gain from analyzing the biologic changes associated with any biologic immunomodulator.