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, 58 (7), 2113-9

Age- And Sex-Related Patterns of Serum Interferon-Alpha Activity in Lupus Families

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Age- And Sex-Related Patterns of Serum Interferon-Alpha Activity in Lupus Families

Timothy B Niewold et al. Arthritis Rheum.

Abstract

Objective: Interferon-alpha (IFNalpha) 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 IFNalpha 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 IFNalpha activity using a functional reporter cell assay. IFNalpha activity was analyzed in relation to age, and subgroups with high levels of IFNalpha 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 IFNalpha 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 IFNalpha activity. The segmentation algorithm revealed significantly increased IFNalpha 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 IFNalpha activity after the age of 50 years.

Conclusion: Serum IFNalpha activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age-related pattern of IFNalpha activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had similar age-related patterns of IFNalpha activity.

Figures

Figure 1
Figure 1
Graphic representation of the best-fit segmentations of serum interferon-α (IFNα) activity data stratified by age in the female and male systemic lupus erythematosus (SLE) patients, their female and male healthy first-degree relatives, and in female and male healthy unrelated donors. The length of the line along the x-coordinate represents the range of ages in each data segment from which the mean was calculated.
Figure 2
Figure 2
Serum interferon-α (IFNα) activity data stratified by individual change points (according to age) in female and male systemic lupus erythematosus (SLE) patients and their female and male healthy first-degree relatives. The age groupings reflect the most significant subgroups within the data that were identified by the Mann-Whitney sliding window segmentation algorithm. The Mann-Whitney t-test was used to show independently significant differences in serum IFNα activity in each age grouping. Bars show the median. P values were determined by Mann-Whitney t-test.
Figure 3
Figure 3
Serum interferon-α activity stratified by sex in systemic lupus erythematosus (SLE) patients, their healthy first-degree relatives, and in healthy unrelated donors. Values are the median and interquartile range. P values were determined by Mann-Whitney t-test.

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