Protein microarray analysis of serum factor-reactive autoantibodies reveals BAFF-binding autoantibodies in systemic lupus erythematosus (58.22)

Abstract

Autoantibodies to cytokines and chemokines have been shown to influence immune pathways in patients afflicted with a range of immune pathology. We hypothesized that a multiplex platform capable of detecting antibodies to cytokines, chemokines and other immune factors would allow us to identify novel biomarkers of immune diseases and uncover new mechanisms of disease pathogenesis. We created a planar microarray containing a library of recombinant human proteins deposited on nitrocellulose-coated slides. We resolved binding of commercially available antibodies to cytokines and chemokines, and detected previously described cytokine reactivity in samples from patients with non-tuberculosis mycobacterium infection and autoimmune polyendocrine syndrome type 1. We further used the arrays to profile samples from three cohorts of systemic lupus erythematosus (SLE) patients. Among several cytokine targets, the significance analysis of microarrays algorithm identified that B-cell activating factor (BAFF)-binding autoantibodies correlated with subgroups of SLE patients. Reactive sera inhibited the activity of BAFF in a reporter cell assay, indicating that BAFF autoantibodies may influence the activity of this critical cytokine in SLE. Our results demonstrate that serum factor protein microarrays can be used to detect novel and potentially relevant autoreactivity to cytokines in human patient samples, and that BAFF-reactive autoantibodies may play a role in the pathophysiology of SLE.