Research Article: Pathogenic autoantibodies targeting DNA repair proteins are shared by cancer patients and healthy children later diagnosed with cancer
Abstract:
The etiology of pediatric cancer remains poorly understood and does not fit the classical view as an age-associated genetic disease, suggesting yet unknown mechanisms might be involved. Using high-density native proteome arrays, we analyzed sera from 375 healthy individuals and patients. We found a significant enrichment of autoantibodies against DNA repair proteins shared by cancer patients and healthy children diagnosed with cancer years later. These autoantibodies were detected in multiple cancer types and exhibited remarkable age-specificity. To explore their potential pathogenic significance, we assessed the ability of serum IgG to penetrate live cells. We confirmed that IgG can indeed enter live intact cells and identified a specific pattern of subcellular localization prevalent in pediatric patients. These findings offer a novel direction for the investigation of etiology of pediatric cancer and cancer in general.
Introduction:
Autoantibodies - antibodies recognizing the body’s own proteins - are common in healthy people but are also involved in autoimmune disorders ( 1 , 2 ). They can be present at birth or can appear shortly after and increase toward older ages ( 3 – 6 ). Antinuclear autoantibodies at low concentrations have been reported in up to 40% of healthy people ( 7 , 8 ). Although the repertoires are highly heterogeneous, many autoantibodies are shared by a large fraction of healthy individuals ( 1 ). The pathogenic effects of…
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