Age- and sex-related patterns of serum interferon-α activity in lupus families

Objective. Interferon-alpha (IFN alpha) levels are elevated in many patients with systemic lupus erythematosus (SLE) and may play a primary role in its pathogenesis. The purpose of this study Was to determine whether serum IFN alpha activity in SLE patients and their healthy first-degree relatives is highest in early adulthood, when the incidence of SLE is greatest. Methods. Serum samples from 315 SLE patients, 359 healthy first-degree relatives, and 141 healthy unrelated donors were measured for IFN alpha activity using a functional reporter cell assay. IFN alpha activity was analyzed in relation to age, and subgroups with high levels of IFN alpha activity were identified within the large data sets using a Mann-Whitney sliding window segmentation algorithm. The significance of each subgrouping was ranked by Kruskal-Wallis testing. Results. Age was inversely correlated with IFN alpha activity in female SLE patients (r = -0.20, P = 0.001) as well as their healthy female first-degree relatives (r -0.16, P = 0.02). In male patients and their healthy male first-degree relatives, there was no significant overall correlation between age and serum IFN alpha activity. The segmentation algorithm revealed significantly increased IFN alpha activity between the ages of 12 and 22 years in female SLE patients and between the ages of 16 and 29 years in male SLE patients. Both male and female healthy first-degree relatives had significantly decreased IFN alpha activity after the age of 50 years. Conclusion. Serum IFN alpha activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age-related pattern of IFN alpha activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had, similar age-related patterns of IFN alpha activity.