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LP-098 Proteomic analysis of histological lesions in lupus nephritis identifies an inflammatory signature of fibrous crescents
  1. Alessandra Ida Celia1,2,
  2. Jeffrey Hodgin3,
  3. Dwita Demeke3,
  4. Avi Rosenberg4,
  5. Laurence S Magder5,
  6. Jill Buyon6,
  7. Betty Diamond7,
  8. Judith James8,
  9. William Apruzzese9,
  10. Paride Fenaroli10,
  11. Derek Fine11,
  12. Jose Monroy-Trujillo11,
  13. Mohamed G Atta11,
  14. Peter Izmirly6,
  15. Michael Belmont6,
  16. Anne Davidson7,
  17. Daniel W Goldman1,
  18. Accelerating Medicines Partnership (AMP) Ra/sle12,
  19. Michelle Petri1 and
  20. Andrea Fava1
  1. 1Rheumatology, Johns Hopkins University, USA
  2. 2Rheumatology, Sapienza University of Rome, Italy
  3. 3Pathology, University of Michigan, USA
  4. 4Pathology, Johns Hopkins University, USA
  5. 5Department of Epidemiology and Public Health, Univeristy of Maryland, USA
  6. 6Rheumatology, NYU Grossman School of Medicine, USA
  7. 7Center for Autoimmune and Musculoskeletal Diseases, Feinstein Institutes for Medical Research, USA
  8. 8Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, USA
  9. 9Division of Rheumatology, Immunology, Allergy, Department of Medicine, Brigham and Women’s Hospital, Boston, USA
  10. 10S.C. Nefrologia e Dialisi, AUSL-IRCCS Reggio Emilia, Italy
  11. 11Nephrology, Johns Hopkins University, USA
  12. 12Multiple institutes, Multiple cities, USA


Background We employed urine proteomics to define the molecular signatures associated with the histological features quantified by the NIH activity and chronicity indices.

Methods We employed urine proteomics to define the molecular signatures associated with the histological features quantified by the NIH activity and chronicity indices.

Results Glomerular and interstitial lesions in lupus nephritis were quantified (scored 0–3) based on the revised 2018 International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification for lupus nephritis and the modified NIH scoring system by a central renal pathologist (JH). Urinary proteins (1200 biomarkers, RayBiotech Kiloplex) were quantified in urine samples collected on the day of (73%) or within 3 weeks of (27%) the diagnostic kidney biopsy. Proteomic signatures of each lesion were defined based on Spearman correlations of each urine protein with each pathologic lesion.

Conclusions Ninety-one biopsies were included: 32 (35%) with pure proliferative LN, 33 (36%) with pure membranous LN, and 26 (29%) with mixed LN. The 5 most correlated urinary proteins and each pathologic feature are summarized in Figure 1A-B. Most lesions in the activity or chronicity indices shared a similar signature within their respective index. In contrast, fibrous crescents displayed an inflammatory signature (CD73, MMP9, MIP1b, and IL-8) despite being part of the NIH chronicity index. Hierarchical clustering based on proteomic signatures revealed that fibrous crescents were more similar to activity-related lesions (figure 1c). Interstitial inflammation (activity) was correlated with biomarkers associated with both active and chronic lesions.

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