Approaches to define early gene expression in sarcoidal granuloma formation have been limited. No animal model for sarcoidosis exists and human studies have been carried out in patient samples obtained at diagnosis or during the disease course. Previous studies performed at Mt. Sinai and elsewhere have shown that the cellular and biochemical granulomatous response to Kveim-Siltzbach (KS) suspension parallels the disease granuloma. Studies of KS injected tissue harvested at weeks 1, 2, 3 and 4 have revealed recruitment of CD4 lymphocytes and macrophages that gradually form the mature epithelioid cells, giant cells, and rim of lymphocytes that form the sarcoidal granuloma. There are no studies of the temporal sequence of gene expression during this time period as granulomas emerge. Gene expression microarray analyses during Kveim maturation offer a unique opportunity to investigate the cascade of molecular biologic events leading to granuloma formation. We propose to recruit 5 to 8 patients who recently had positive KS tests for the diagnosis of their illness. Four subcutaneous injections will be performed. Sites will be biopsied a 1 day, 1 week, 2 weeks, and 4 weeks after incubation of KS suspension. For controls each patient will have a biopsy of normal skin. Gene expression profiles will be determined by microarray analysis and related to histological changes. Gene expression results by microarray will be verified by RT PCR and immunohistochemisty. Identifying genes expressed in response to the KS suspension will provide new information about the initiation of granuloma formation, give greater direction to future studies and could help identify new potential targets for intervention.
|Iannuzzi, Michael C; Rybicki, Benjamin A; Teirstein, Alvin S (2007) Sarcoidosis. N Engl J Med 357:2153-65