Sarcoidosis

About: Sarcoidosis is a research topic. Over the lifetime, 6063 publications have been published within this topic receiving 107024 citations. The topic is also known as: Boeck sarcoid & benign lymphogranulomatosis.

Pulmonary sarcoidosis: a disorder mediated by excess helper T-lymphocyte activity at sites of disease activity.

Abstract: Using the monoclonal antibodies OKT4 and OKT8, we determined the proportions of helper and suppressor T cells in patients with sarcoidosis and high-intensity alveolitis, patients with sarcoidosis and low-intensity alveolitis, patients with idiopathic pulmonary fibrosis (IPF), and normal controls. In controls and patients with IPF, the ratio of helper to suppressor T cells was 1.8:1 in lungs and blood. In contrast, this ratio was 10.5:1 in lungs (P less than 0.001) and 0.8:1 in blood (P less than 0.05) in patients with sarcoidosis and high-intensity alveolitis. The ratio of helper to suppressor T cells was not higher in the lungs or blood of patients with sarcoidosis and low-intensity alveolitis; on the contrary, because of the higher proportions of suppressor cells, the ratio of helper to suppressor cells was lower in both lungs and blood. In studies of function, lung T cells from patients with sarcoidosis and high-intensity alveolitis released monocyte chemotactic factor (a lymphokine critical to granuloma formation) and polyclonally activated B cells to produce immunoglobulins. We conclude that one determinant of lung injury in sarcoidosis in the presence of large numbers of lung helper T cells, which are important in granuloma formation.

Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement.

Abstract: RATIONALE: Evidence suggests that tumor necrosis factor (TNF)-alpha plays an important role in the pathophysiology of sarcoidosis. OBJECTIVES: To assess the efficacy of infliximab in sarcoidosis. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study was conducted in 138 patients with chronic pulmonary sarcoidosis. Patients were randomized to receive intravenous infusions of infliximab (3 or 5 mg/kg) or placebo at Weeks 0, 2, 6, 12, 18, and 24 and were followed through Week 52. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the change from baseline to Week 24 in percent of predicted FVC. Major secondary efficacy parameters included Saint George's Respiratory Questionnaire, 6-min walk distance, Borg's CR10 dyspnea score, and the proportion of Lupus Pernio Physician's Global Assessment responders for patients with facial skin involvement. Patients in the combined infliximab groups (3 and 5 mg/kg) had a mean increase of 2.5% from baseline to Week 24 in the percent of predicted FVC, compared with no change in placebo-treated patients (p = 0.038). No significant differences between the treatment groups were observed for any of the major secondary endpoints at Week 24. Results of post hoc exploratory analyses suggested that patients with more severe disease tended to benefit more from infliximab treatment. CONCLUSIONS: Infliximab therapy resulted in a statistically significant improvement in % predicted FVC at Week 24. The clinical importance of this finding is not clear. The results of this Phase 2 clinical study support further evaluation of anti-TNF-alpha therapy in severe, chronic, symptomatic sarcoidosis.

Endotoxin-induced uveitis in rats as a model for human disease.

Abstract: Acute anterior uveitis is a relatively common disease of uncertain aetiology. Its association with a wide variety of systemic disorders including ankylosing spondylitis, Reiter's syndrome, Behcet's disease, juvenile rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease and sarcoidosis and the prevalence of the HLA antigen B27 (ref. 1) in cases without associated disease have been noted but not explained. In general, animal models for uveitis have not clarified the mechanism of human disease. Most require direct intravitreal injection2 or repeated immunizations with retinal or uveal antigens3. Uveitis does occur in adjuvant arthritis, a syndrome that can be produced in rats by the systemic injection of pepti-doglycan from the cell wall of a variety of Gram-positive bacteria4. The disease, which was initially described following the injection of mycobacteria in mineral oil, has many similarities to Reiter's syndrome5, including the development of eye pathology in as many as 40% of the animals6. As Reiter's syndrome is associated with enteric Gram-negative infections such as Shigella, Salmonella and Yersinia, we sought to produce an arthritis in rats by injecting killed Gram-negative bacteria. Although we have not observed clinical arthritis in these animals, careful histological study has shown the near-universal appearance of uveitis. The studies described below indicate that the eye disease is due to a portion of the bacterial cell wall known as endotoxin or lipopolysaccharide (LPS).