Increased risk of autoimmune disease in families with Wegener's granulomatosis.

Objective: The etiology of Wegener's granulomatosis (WG) is unknown. Susceptibility genes for WG that also affect the risks of other autoimmune/inflammatory diseases have been identified, indicating the existence of shared interdisease genetic susceptibilities. To determine the effect, on a population level, of shared susceptibility on disease risk, we assessed the occurrence of autoimmune/inflammatory disease in first-degree relatives of patients with WG.

Methods: In the Swedish Hospital Discharge Register we identified 2288 individuals discharged with the diagnosis of WG between 1970 and 2003. Through linkage to the Swedish Multi-generation Register we identified 787 parents, 1212 siblings, and 3650 children of these patients. From the Register of Total Population we identified 10 controls for each patient with WG, and 65,000 of their first-degree relatives. Through linkage to the nationwide Outpatients Register, we identified autoimmune/inflammatory disease among all relatives. Relative risks were estimated as hazard ratio (HR) using Cox regression. The study period was 2001-2006.

Results: Biological first-degree relatives of patients with WG were at a moderately increased risk of any autoimmune/inflammatory disease (HR 1.32, 95% CI 1.18-1.49), including specific associations with, for example, multiple sclerosis (HR 1.92, 95% CI 1.16-3.16), Sjögren's syndrome (HR 2.00, 95% CI 1.07-3.73), and seropositive rheumatoid arthritis (HR 1.54, 95% CI 1.09-2.19).

Conclusion: Relatives of patients with WG are at increased risk of being diagnosed with other autoimmune/inflammatory diseases, indicating shared susceptibility between WG and other auto-immune/inflammatory disease.