PMC8141750_01
Tumor assessment during tislelizumab treatment. (A) Baseline before treatment. (B) After two cycles of induction treatment. (C) After four cycles of induction treatment. (D) At membranous nephropathy diagnosis.
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Partial response was achieved and persisted after 2 cycles ( Figure 1 ).
Renal biopsy findings showing a THSD7A-associated MN Renal histology specimens and baseline tumor tissue. (A) Periodic acid-Schiff (PAS) stain showing stiff glomeruli (Original magnification, 400x). (B) Masson trichrome stain showing subepithelially localized immune deposits (green arrow) (Original magnification, 400x). (C) Immunofluorescence of IgG deposition in the subepithelial area. (Original magnification, 200x). (D) Immunofluorescence of subepithelial IgG1 deposition. (Original magnification, 200x). (E) Immunofluorescence of subepithelial IgG2 deposition. (Original magnification, 200x). (F) Immunofluorescence of subepithelial IgG4 deposition. (Original magnification, 200x). (G) Electron microscopy showing discrete electron-dense subepithelial deposits (red arrow). (Original magnification, 6000x). (H) Positive staining for thrombospondin type-1 domain-containing 7A (THSD7A) along the glomerular basement membrane. (Original magnification x 200). (I) The tumor cells of baseline metastases lymph node were positive for thrombospondin type-1 domain-containing 7A (THSD7A) by immunohistochemistry (blue arrows).
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Light microscopy showed stiffness in the glomeruli with scattered subepithelially localized immune deposits (Masson stain) containing slightly focal tubular atrophy and interstitial fibrosis, consistent with early MN ( Figures 2A, B ). Immunofluorescence staining showed granular immunoglobulin G (IgG) deposits ( Figure 2C ), including IgG1, IgG2 and IgG4, uniformly and subepithelially distributed in the glomeruli ( Figures 2D-F ). Electron microscopy showed discrete electron-dense deposits at the subepithelial surface of the glomerular capillary wall, accompanied by effacement of overlying epithelial cell foot processes ( Figure 2G ). Immunohistochemical analyses revealed positive staining for THSD7A along the glomerular basement membrane ( Figure 2H ). THSD7A antigen tested positive ( Figure 2I ). The patient tested negative for THSD7A antibodies at baseline but tested positive after 4 cycles of maintenance tislelizumab therapy ( Figure 3 ). Therefore, MN was thought to be related with the ICI treatment.
Series anti-thrombospondin type-1 domain-containing 7A (THSD7A) antibody tests. THSD7A IgG detected in the serum using cell-based indirect immunofluorescence test. Images on the top show transfection cells express green fluorescent protein. The images on the bottom show transfected cells with the red fluorescent-labeled secondary antibody on detection of anti-THSD7A IgG. (A) Negative control. (B) Baseline before treatment (June 19, 2019). (C) After four cycles of induced treatment (September 20, 2019). (D) After four cycles of maintenance therapy (December 12, 2019). (E) At nephrotic syndrome diagnosis (May 12, 2020). (F) Positive control.
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THSD7A antigen tested positive ( Figure 2I ). The patient tested negative for THSD7A antibodies at baseline but tested positive after 4 cycles of maintenance tislelizumab therapy ( Figure 3 ). Therefore, MN was thought to be related with the ICI treatment.