Exostosin 1 and exostosin 2 (EXT1/EXT2) on glomerular basement membrane (GBM) were recently reported as novel putative antigens in secondary membranous nephropathy with autoimmune disease. However, the clinical significance of glomerular EXT1/EXT2 remains elusive in patients with lupus nephritis (LN). The immunofluorescence staining pattern of glomerular EXT1/EXT2 is also undetermined in membranous LN (MLN) or proliferative LN (PLN). We cross-sectionally analyzed patients with MLN (pure class V, n = 11) and PLN (class III, IV, and mixed class III/IV + V, n = 22) who underwent renal biopsies between 2010 and 2020 at Showa University Hospital. Glomerular EXT1/EXT2 expressions were evaluated by immunofluorescence. T-helper (Th) cell-related serum inflammatory cytokines were measured using enzyme-linked immunosorbent assay. The positivity for both EXT1/EXT2 was higher in patients with MLN than PLN (90.9% vs 63.6%, P = 0.212). MLN showed global and bright granular EXT1/EXT2 expressions along GBM, while PLN showed segmental and moderate expressions on GBM. Additionally, glomerular EXT1/EXT2 positivity was not associated with the degree of proteinuria or renal function in MLN and PLN patients, but the levels of serum anti-dsDNA antibody and circulating immune complexes were lower in patients with EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Moreover, serum complement levels and IL-4/IFN-γ ratios were elevated in EXT1/EXT2-positive MLN than EXT1/EXT2-negative PLN. Collectively, immunofluorescence staining for glomerular EXT1/EXT2 had characteristic patterns between MLN and PLN. Glomerular EXT1/EXT2 expressions tended to be high in Th2-dominant MLN patients without severe hypocomplementemia and elevated autoantibodies. Thus, EXT1/EXT2 might be involved in the unique developmental mechanism of MLN.

肾小球基底膜 (GBM) 上的外泌体素 1 和外泌体素 2 (EXT1/EXT2) 最近被报道为继发性膜性肾病伴自身免疫性疾病的新型推定抗原。然而，肾小球 EXT1/EXT2 在狼疮性肾炎 (LN) 患者中的临床意义仍然难以捉摸。肾小球 EXT1/EXT2 的免疫荧光染色模式在膜性 LN (MLN) 或增殖性 LN (PLN) 中也未确定。我们横断面分析了 MLN（纯 V 类，n  = 11）和 PLN（III、IV 类和混合 III/IV + V 类，n = 22) 于 2010 年至 2020 年期间在昭和大学医院接受了肾活检。通过免疫荧光评估肾小球 EXT1/EXT2 表达。使用酶联免疫吸附测定法测量 T 辅助 (Th) 细胞相关的血清炎性细胞因子。MLN 患者的 EXT1/EXT2 阳性率高于 PLN（90.9% vs 63.6%，P = 0.212）。MLN 沿 GBM 显示全局和明亮的颗粒 EXT1/EXT2 表达，而 PLN 在 GBM 上显示节段性和中度表达。此外，肾小球 EXT1/EXT2 阳性与 MLN 和 PLN 患者的蛋白尿程度或肾功能无关，但 EXT1/EXT2 阳性 MLN 患者的血清抗 dsDNA 抗体和循环免疫复合物水平低于 EXT1 /EXT2 负 PLN。此外，EXT1/EXT2 阳性 MLN 的血清补体水平和 IL-4/IFN-γ 比值高于 EXT1/EXT2 阴性 PLN。总的来说，肾小球 EXT1/EXT2 的免疫荧光染色在 MLN 和 PLN 之间具有特征模式。在没有严重低补体血症和自身抗体升高的 Th2 主导型 MLN 患者中，肾小球 EXT1/EXT2 表达往往较高。因此，