Characterization of Type-I IFN subtype autoantibodies and activity in SLE serum and urine

被引:12
|
作者
Harris, Bethany D. [1 ]
Kuruganti, Srilalitha [1 ,2 ]
Deshpande, Ashlesha [1 ]
Goepfert, Paul A. [3 ]
Chatham, W. Winn [4 ]
Walter, Mark R. [1 ]
机构
[1] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
[2] Boehringer Ingelheim GmbH & Co KG, St Joseph, MO USA
[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
基金
芬兰科学院;
关键词
Systemic lupus erythematosus; interferon subtypes; cytokines; autoantibodies; serum; urinalysis; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLONY-STIMULATING FACTOR; INTERFERON-ALPHA; ANTI-INTERFERON; ANTIBODIES; CELLS; ANIFROLUMAB; ASSOCIATION; ACTIVATION; SIGNATURE;
D O I
10.1177/0961203320935976
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background/objective Type-I interferons contribute to pathogenesis in systemic lupus erythematosus, including nephritis. Interferons consist of a family of 16 proteins yet are often characterized in patients without knowledge of the specific interferon subtypes involved. Different interferons may function in the kidneys, and other organs, relative to what is often measured in patient blood. Moreover, antibodies to interferons may potentially modulate systemic or organ-specific interferon activity. The aim of this study was to characterize global interferon activity levels and identify autoantibodies to the 12 interferon alpha subtypes in patient serum and urine. Methods Interferon activity levels in serum and urine were measured using an interferon bioassay. Anti-interferon and anti-cytokine autoantibodies were measured by ELISA. Serum and urine samples were also characterized for their ability to neutralize the biological activity of exogenously added interferons. Results Serum interferon activity was increased in 62% of systemic lupus erythematosus patient samples, relative to healthy donor controls, whereas binding interferon alpha autoantibodies to at least one interferon alpha subtype were found in 68% of the samples evaluated. High Systemic Lupus Erythematosus Disease Activity Index scores were significantly (p = 0.001) associated with patient samples containing interferon alpha autoantibodies to three or more interferon alpha subtypes in their serum. Interferon alpha autoantibodies that potently block interferon activity were rare (similar to 5% of samples), but collectively bound to all 12 interferon alpha subtypes. Urine interferon activity and interferon alpha autoantibody profiles did not correlate with their serum counterparts, suggesting immune responses in systemic lupus erythematosus kidneys can be distinct from those measured in serum. Analysis of autoantibodies to 15 additional cytokines in serum identified higher frequencies of granulocyte-macrophage colony-stimulating factor and interleukin 17A autoantibodies, suggesting these signaling pathways may potentially contribute, with interferons, to systemic lupus erythematosus pathogenesis. Conclusions The measurement of autoantibodies to multiple interferon subtypes in serum and urine may provide an alternative method for following interferon-mediated systemic lupus erythematosus disease activity. The results suggest autoantibodies might be used for patient monitoring and/or identifying additional cytokine signaling pathways that are functioning in different systemic lupus erythematosus patients.
引用
收藏
页码:1095 / 1105
页数:11
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