Neutrophil Extracellular Traps (NETs): An unexplored territory in renal pathobiology, a pilot computational study

摘要

In the age of modern medicine and artificial intelligence, image analysis and machine learning have revolutionizeddiagnostic pathology, facilitating the development of computer aided diagnostics (CADs) which circumvent prevalentdiagnostic challenges. Although CADs will expedite and improve the precision of clinical workflow, their prognosticpotential, when paired with clinical outcome data, remains indeterminate. In high impact renal diseases, such asdiabetic nephropathy and lupus nephritis (LN), progression often occurs rapidly and without immediate detection, dueto the subtlety of structural changes in transient disease states. In such states, exploration of quantifiable imagebiomarkers, such as Neutrophil Extracellular Traps (NETs), may reveal alternative progression measures whichcorrelate with clinical data. NETs have been implicated in LN as immunogenic cellular structures, whose occurrenceand dysregulation results in excessive tissue damage and lesion manifestation. We propose that renal biopsy NETdistribution will function as a discriminate, predictive biomarker in LN, and will supplement existing classificationschemes. We have developed a computational pipeline for segmenting NET-like structures in LN biopsies. NET-likestructures segmented from our biopsies warrant further study as they appear pathologically distinct, and resemble nonlytic,vital NETs. Examination of corresponding H&E regions predominantly placed NET-like structures in glomeruli,including globally and segmentally sclerosed glomeruli, and tubule lumina. Our work continues to explore NET-likestructures in LN biopsies by: 1.) revising detection and analytical methods based on evolving NETs definitions, and2.) cataloguing NET morphology in order to implement supervised classification of NET-like structures inhistopathology images.