PMC5505917_01
Renal biopsy on admission. A: Twenty-two glomeruli were observed. Note the lack of global sclerosis, thrombi, wire loop lesions, spike formation, fibrinoid necrosis or crescent [Hematoxylin and Eosin (H&E) staining, 200x]. B: Immunoglobulin G deposition in the capillary walls and mesangial areas, and C3 deposition in mesangial areas (immunofluorescence stain, 100x). C: Vasculitis of intralobular arteries with fibrinoid necrosis, inflammatory infiltrates, and destruction of the vascular wall (H&E staining or Periodic acid-Schiff stain, 100x).
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H&E-stained renal biopsy tissue showed normal glomeruli (Fig. 1A). However, marked deposition of complement and IgG in the glomeruli was noted in immunofluorescence staining (Fig. 1B). This included fibrinoid necrosis, prominent infiltration around the blood vessel wall with inflammatory cells including lymphocytes, and tears of the elastic laminae of the arteries (Fig. 1C).
P-glycoprotein expression on peripheral CD19+ cells and infiltrated CD19+ cells around small vessels in the kidney. A: P-gp expression on CD4+ and CD19+ cells before treatment with prednisolone. The dotted line represents the gate set to discriminate negatively from positively stained cells as determined by control FITC-conjugated anti-mouse IgG Ab. The data represent the percentages of P-gp-positively stained CD4+ and CD19+ cells. B: Immunostaining for CD19+ lymphocytes using anti-CD19 monoclonal antibody (mAb) with 3.3'-diaminobenzidine (DAB) (brown color). C: Immunostaining for P-gp on lymphocytes using JSB-1 anti-P-gp mAb (P-gp) or isotype-matched negative control antibody immunoglobulin G1 (IgG1 control) with Vulcan Fast Red (FR) (red color). B, C: Nuclear counterstaining with hematoxylin.
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The percentages of P-gp-positively stained CD4+ and CD19+ peripheral lymphocytes were 7.0% and 40.1%, respectively (Fig. 2A). Marked infiltration of CD19+ lymphocytes and P-gp-positive lymphocytes was noted in the perivascular area of vasculitis; therefore, the P-gp+ CD19+ lymphocytes were suggested to have accumulated around the vasculitis (Fig. 2B, C).
Clinical course. PSL: prednisolone, IVCY: intravenous cyclophosphamide pulse therapy, SLEDAI: systemic lupus erythematosus disease activity index score, U-prot: urinary protein, Cre: creatinine, CH50: 50% hemolytic complement activity, anti-ds DNA Ab: anti-double-stranded (ds) DNA antibody
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IVCY (15 mg/kg/day) combined with oral betamethasone (equivalent to 1.0 mg/kg/day of prednisolone) (Fig. 3). Immediate clinical improvement was noted after two courses of biweekly IVCY, along with normalization of the ESR, complement and anti-ds DNA antibody, followed by clinical remission (SLEDAI score: 0). Under such treatment, the clinical remission and normal renal function were maintained for more than three years (Fig. 3).