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Mass Spectrometry With Data-Independent Acquisition for the Identification of Target Antigens in Membranous Nephropathy

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➡️ doi.org/10.1053/j.aj...

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14/ The presence of the suspected target antigen was confirmed by confocal microscopy and relevant disease associations were found with specific antigens (e.g., NELL1 in malignancy; NCAM1 in MCTD; NDNF in syphilis-associated MN) – supporting the clinical relevance of antigen typing in MN

12/ Compared to DDA, the more comprehensive/sensitive DIA:
- Increased the number of proteins (3800 vs 1200) identified in healthy glomeruli;
- Allowed the detection of all known antigens except NELL1 in normal glomeruli;
- Increased the detection rate of antigens from 46% to 83% in PLA2R-neg MN

9/ Glomeruli from patients with PLA2R-MN showed enrichment in specific pathways (immune response, complement activation, B cell-mediated immunity) and an increased abundance of the target antigen PLA2R, IgG4, and complement proteins (C3, C5, C9, CFH, FHR2, FHR5) - as expected

8/ Compared to tubulointerstitium, healthy glomeruli were enriched in glomerular-specific proteins with key roles in the integrity of the glomerular filtration barrier, and in specific pathways involved in cytoskeleton organization, actin binding, glomerulus development and cell adhesion

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Editorial: journals.sagepub.com/eprint/ENYAN...

Original article: journals.sagepub.com/doi/10.1177/...