FP130
A CROSS-SECTIONAL ANALYSIS OF CLINICOPATHOLOGIC SIMILARITY AND DISTINCTION BETWEEN HENOCH-SCHOLEIN PURPURA NEPHRITIS AND IGA NEPHROPATHY Free

INTRODUCTION: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) have similar pathologic abnormalities. Recent studies noted that the two diseases share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis. However, there are also distinct clinical dissimilarities. Therefore, we aimed to clarify the clinicopathologic distinction between HSPN and IgAN.

METHODS: We cross-sectionally evaluated clinicopathological characteristics of adult patients with HSPN (n=24) or IgAN (n=56), who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital. Six patients with minimal change disease (MCD) were enrolled as normal controls. Serum Gd-IgA1 (s-Gd-IgA1) levels at the time of RB were compared among study groups using ELISA with an anti-human Gd-IgA1-specific monoclonal antibody (KM55). We also immunohistochemically stained paraffin-embedded sections for glomerular Gd-IgA1-deposition using KM55. Serum inflammatory cytokines were measured by ELISA.

RESULTS: Compared with patients with IgAN, patients with HSPN underwent RB earlier after onset of urinary abnormality and received steroid therapy at higher rate. Although glomerular lesions and tubulointerstitial injury were significantly worse in patients with IgAN, glomerular fibrin deposition and endothelial injury with subendothelial IgA deposition were still significant in patients with HSPN. Serum IL-8, MCP-1, TNF-α, and IL-6 levels were significantly higher in patients with HSPN than IgAN, and were significantly correlated with serum IgA levels. Elevation of s-Gd-IgA1 levels as compared to those in MCD (5.2 ± 1.8 μg/mL) were comparable among patients with HSPN and IgAN (HSPN vs. IgAN: 13.1 ± 9.7 vs. 16.1 ± 10.2 μg/mL, p=0.246), and a similar degree of mesangial-Gd-IgA1 (m-Gd-IgA1) deposition was detected in both diseases. Furthermore, m-Gd-IgA1 deposition was evident in patients with histopathologically advanced HSPN or IgAN. In patients with HSPN, a significant positive correlation between s-Gd-IgA1 and IL-6 (r=0.487, p<0.001) was confirmed, and m-Gd-IgA1 intensity was significantly correlated with IL-8 and MCP-1 elevations (IL-8: r=0.165, p=0.052; MCP-1: r=0.197, p=0.031) or crescent formation. Patients with IgAN showed no correlation of inflammatory cytokines with Gd-IgA1. Remarkably, in patients with HSPN, skin biopsy specimens obtained from purpura that developed before nephritis showed no deposition of Gd-IgA1, but only IgA1.

CONCLUSIONS: We consider that HSPN might exhibit glomerular capillaritis, as a symptom of systemic vasculitis-like purpura, with significant elevation of inflammatory cytokines associated with glomerular damage, s-Gd-IgA1 elevation, and m-Gd-IgA1 deposition. HSPN may have different type of nephritis not associated with Gd-IgA1 as well as simultaneously share the Gd-IgA1-oriented nephritis seen with IgAN.