Abstract：
OBJECTIVE: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes.
METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.
RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.
CONCLUSIONS: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.
METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.
RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.
CONCLUSIONS: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.
摘要：
目的：异二聚体外生骨素-1/外生骨素-2（EXO-1/2）是在与系统性红斑狼疮相关的膜性肾病中观察到的新型抗原。本研究旨在评估肾脏活检中EXO-1/2阳性与肾脏预后之间的关联。
方法：对50例5类狼疮性肾炎（LN）和55例3/4+5类混合LN患者的肾活检组织进行EXO-1/2染色。比较EXO-1/2阳性和EXO-1/2阴性患者的基线临床和组织学特征。进行事件发生时间分析以比较对治疗的反应率，肾耀斑,进展为肾小球滤过率(eGFR)下降40%，血清肌酐加倍,和肾衰竭。
结果：第5类50人中有14人（28%），第3/4+5类混合类LN55人中有5人（9%）对EXO-1/2呈阳性。5级LN和EXO-1/2阳性染色的患者较年轻，有更好的肾功能，和减少肾活检分析中的疤痕。超过100个月的中位随访时间，在整个队列中,EXO-1/2染色阳性的患者的进展率显著较低.当在第5类和混合类LN子群中单独分析时，eGFR下降40%的进展率显著较低,血清肌酐和肾衰竭倍增的趋势无统计学意义.
结论：EXO-1/2是在5类LN中检测到的新型抗原，与肾功能的良好预后相关。在临床实践中掺入EXO-1/2染色可能由于其预后意义而潜在地改变LN的管理。要点•在与自身免疫性疾病如系统性红斑狼疮相关的膜性肾病病例中发现外泌素-1/外泌素-2抗原。•在5类或3/4+5类混合狼疮性肾炎的肾活检中，外生骨素-1/外生骨素-2染色与肾功能的良好长期预后相关。•将外生骨素-1/外生骨素-2染色纳入临床实践可能由于其预后影响而潜在地改变管理。
方法：对50例5类狼疮性肾炎（LN）和55例3/4+5类混合LN患者的肾活检组织进行EXO-1/2染色。比较EXO-1/2阳性和EXO-1/2阴性患者的基线临床和组织学特征。进行事件发生时间分析以比较对治疗的反应率，肾耀斑,进展为肾小球滤过率(eGFR)下降40%，血清肌酐加倍,和肾衰竭。
结果：第5类50人中有14人（28%），第3/4+5类混合类LN55人中有5人（9%）对EXO-1/2呈阳性。5级LN和EXO-1/2阳性染色的患者较年轻，有更好的肾功能，和减少肾活检分析中的疤痕。超过100个月的中位随访时间，在整个队列中,EXO-1/2染色阳性的患者的进展率显著较低.当在第5类和混合类LN子群中单独分析时，eGFR下降40%的进展率显著较低,血清肌酐和肾衰竭倍增的趋势无统计学意义.
结论：EXO-1/2是在5类LN中检测到的新型抗原，与肾功能的良好预后相关。在临床实践中掺入EXO-1/2染色可能由于其预后意义而潜在地改变LN的管理。要点•在与自身免疫性疾病如系统性红斑狼疮相关的膜性肾病病例中发现外泌素-1/外泌素-2抗原。•在5类或3/4+5类混合狼疮性肾炎的肾活检中，外生骨素-1/外生骨素-2染色与肾功能的良好长期预后相关。•将外生骨素-1/外生骨素-2染色纳入临床实践可能由于其预后影响而潜在地改变管理。
