Clustering of immune-mediated diseases in sarcoidosis.

Abstract

Sarcoidosis is an immune-mediated disease of unknown cause. Immune-mediated diseases appear to cluster in patients and in families. We review what is known on this topic for sarcoidosis, and what factors may underlie disease clustering. In populations of patients with sarcoidosis, relative risk estimates of Sjögren's syndrome, systemic lupus erythematosus, autoimmune hepatitis, ankylosing spondylitis, multiple sclerosis (MS), celiac disease, autoimmune thyroid disease, and ulcerative colitis, varied between 2.1 and 11.6. In relatives of patients with sarcoidosis, relative risk estimates varied between 1.3 and 5.8 for sarcoidosis, MS, celiac disease, type 1 diabetes, Graves' disease, rheumatoid arthritis, Crohn's disease, and ulcerative colitis. Shared risk loci in key immunological pathways provide evidence for a contribution to development of multiple diseases. Identical changes in the immune status, epigenetic alterations, and environmental triggers have been detected in several diseases, and drug-induced disease is likely responsible for a small portion of co-occurring disease. Clustering of sarcoidosis and other immune-mediated diseases in patients and in their relatives occurs for sarcoidosis, MS, celiac disease, Graves' disease, and ulcerative colitis. Further research is needed to substantiate causal links and risk estimates in patients and their relatives.