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Abstract：
OBJECTIVE: Accumulating evidence supports the use of antineutrophil cytoplasmic antibody (ANCA) type to classify different clinical entities. We aimed to evaluate whether the presence and type of ANCA determine different diseases, based on clinical phenotypes, renal involvement, and response to treatment.
METHODS: Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%.
RESULTS: A total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006).
CONCLUSIONS: Clinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).
METHODS: Differences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%.
RESULTS: A total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006).
CONCLUSIONS: Clinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).
摘要：
目的：越来越多的证据支持使用抗中性粒细胞胞浆抗体（ANCA）类型对不同的临床实体进行分类。我们的目的是评估ANCA的存在和类型是否决定了不同的疾病，基于临床表型，肾受累,以及对治疗的反应。
方法：临床表现方面的差异，疾病活动,实验室参数,和组织学记录的患者局灶性坏死性肾小球肾炎（FNGN）由于髓过氧化物酶（MPO-），蛋白酶3-ANCA(+)[PR3-ANCA(+)],和诊断时的ANCA（-）疾病。患者接受相同的治疗方案并随访24个月，在计划的基础上，第一年每个月和第二年每3个月。主要终点是：（i）合并终末期肾病（ESRD）和/或死亡；（ii）随访期间主要或次要复发的存在以及次要终点是ESRD和估计肾小球滤过率降低（eGFR）≥50％。
结果：共有92例患者（M/F39/53，平均年龄59.1±15岁）因ANCA相关血管炎（AAV）而被诊断为FNGN，36例（39.1%）患者诊断为PR3-ANCA，39例（42.4%）患者诊断为MPO-ANCA，纳入17例(18.5%)被诊断为ANCA(-)的患者.涉及的系统数量在PR3-、MPO-ANCA,ANCA(-),3、25.5和29％的患者仅肾脏受累，两个系统涉及33％，31％和59％的患者，>3个系统涉及64、43.5和12%的患者，分别(p=0.002)。组织学分类显示病灶，月牙形,混合,和硬化型在14、64、19和3%的PR3-ANCA(+)，8、28、18和46%的MPO-ANCA，和41％、29％、6％和24％的ANCA（-），分别(p<0.0001)。ESRD±死亡的主要终点为11（30.6％），16（41%），6例（35.5%）PR3-ANCA（+）患者，MPO-ANCA(+),ANCA(-),分别(p=NS)；类似地，ESRD±>50%eGFR降低8（22.2%），15（38.5%），5名(29.4%)患者，分别（p=NS），意味着MPO-ANCA(+)患者有肾功能下降的倾向。PR3-ANCA（+）患者的复发率增加，14（38.9%），4（11.8%），和2（10.3％）的PR3-ANCA（+）患者，MPO-ANCA(+),ANCA(-),在两年的随访中至少有一次复发（p=0.006）。
结论：PR3-ANCA(+)之间的临床表型和肾脏组织学差异显著，MPO-ANCA(+),和ANCA(-)疾病和FNGN；然而，肾功能结果相似，尽管PR3-ANCA（）患者的复发率增加。
方法：临床表现方面的差异，疾病活动,实验室参数,和组织学记录的患者局灶性坏死性肾小球肾炎（FNGN）由于髓过氧化物酶（MPO-），蛋白酶3-ANCA(+)[PR3-ANCA(+)],和诊断时的ANCA（-）疾病。患者接受相同的治疗方案并随访24个月，在计划的基础上，第一年每个月和第二年每3个月。主要终点是：（i）合并终末期肾病（ESRD）和/或死亡；（ii）随访期间主要或次要复发的存在以及次要终点是ESRD和估计肾小球滤过率降低（eGFR）≥50％。
结果：共有92例患者（M/F39/53，平均年龄59.1±15岁）因ANCA相关血管炎（AAV）而被诊断为FNGN，36例（39.1%）患者诊断为PR3-ANCA，39例（42.4%）患者诊断为MPO-ANCA，纳入17例(18.5%)被诊断为ANCA(-)的患者.涉及的系统数量在PR3-、MPO-ANCA,ANCA(-),3、25.5和29％的患者仅肾脏受累，两个系统涉及33％，31％和59％的患者，>3个系统涉及64、43.5和12%的患者，分别(p=0.002)。组织学分类显示病灶，月牙形,混合,和硬化型在14、64、19和3%的PR3-ANCA(+)，8、28、18和46%的MPO-ANCA，和41％、29％、6％和24％的ANCA（-），分别(p<0.0001)。ESRD±死亡的主要终点为11（30.6％），16（41%），6例（35.5%）PR3-ANCA（+）患者，MPO-ANCA(+),ANCA(-),分别(p=NS)；类似地，ESRD±>50%eGFR降低8（22.2%），15（38.5%），5名(29.4%)患者，分别（p=NS），意味着MPO-ANCA(+)患者有肾功能下降的倾向。PR3-ANCA（+）患者的复发率增加，14（38.9%），4（11.8%），和2（10.3％）的PR3-ANCA（+）患者，MPO-ANCA(+),ANCA(-),在两年的随访中至少有一次复发（p=0.006）。
结论：PR3-ANCA(+)之间的临床表型和肾脏组织学差异显著，MPO-ANCA(+),和ANCA(-)疾病和FNGN；然而，肾功能结果相似，尽管PR3-ANCA（）患者的复发率增加。
