儿童抗中性粒细胞胞浆抗体相关性小血管炎的临床病理特点分析

目的探讨儿童抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎的临床表现、血清ANCA和肾脏病理检查特征以及其治疗转归情况.方法采用间接免疫荧光定性检查血清ANCA,以酶联免疫吸附分析(ELISA)定量测定患儿血清抗蛋白酶3(PR3)和抗髓过氧化物酶(MPO)抗体活性,并同时进行肾穿刺病理检查,对5例ANCA相关性小血管炎(ASV)患儿的临床表现、血清ANCA与肾活检结果及治疗转归情况进行分析.结果 (1) 5例ASV患儿占同期肾脏疾病住院患儿的0.25%,发病年龄在8～12岁之间,平均10岁6个月,均为女孩.(2) 5例ASV患儿血清胞浆型ANCA阴性,抗PR3定量都在正常范围内,环核型ANCA均阳性,抗MPO 98～242 kEU/L,平均154.5 kEU/L(正常<12.7 kEU/L).(3) 5例患儿均为ANCA相关性小血管炎中的显微镜下多动脉炎,肾脏病理改变均为广泛新月体形成,并有毛细血管袢纤维素样坏死,免疫荧光检查有不同程度的C3沉积,除1例IgA和IgM沉积较强外,免疫球蛋白沉积均较弱.电镜下显示沉积部位主要在内皮下,1例在GBM内也有沉积.(4) 5例患儿中有3例在确诊后1年内死亡,2例经甲泼尼龙和环磷酰胺冲击后,肾功能恢复至正常,分别随访1年和5年,留有血尿和少量蛋白尿.结论儿童ASV女孩占绝大多数,以环核型ANCA为主,较成人更易出现肾功能衰竭,预后也更为严峻,血清ANCA定性定量检查与肾活检是诊断儿童ASV的关键.

Clinical and pathological characterization of antineutrophil cytoplasmic antibody associated small vasculitis in children

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA) associated small vasculitides (ASV) are rare in children and often complicated in clinical manifestations and have very poor prognosis. In order to deepen our understanding of ANCA-associated small vasculitis (ASV) in children, the present study aimed to characterize their clinical manifestations, serum ANCA and renal histopathological findings and outcomes in Chinese children. METHODS: Serum ANCA was qualitatively tested with indirect immunofluorescence microscopy and anti-proteinase 3 (PR(3)) and anti-myeloperoxidase (MPO) activity were quantitated by enzyme-linked immunosorbent assays (ELISA), and renal biopsies were done to investigate the pathological changes. The clinical manifestation, serum ANCA and renal histopathological findings and outcome were characterized in 5 children with ANCA associated small vasculitis. RESULTS: (1) Five children with ANCA associated small vasculitis only accounted for 1.20% of children in whom renal biopsy was performed and 0.25% of hospitalized children with renal diseases during the same period. The age of onset of the 5 children with ASV was between 8 to 12 years with mean age 10.5 years. All ASV children were female. (2) All ASV children were negative for C-ANCA and showed normal anti-proteinase 3 activities, but positive for P-ANCA with high anti-myeloperoxidase activities between 98 to 242 kEU/L. The mean value of MPO-ANCA was 154.5 kEU/L (normal range < 12.7 kEU/L). (3) All ASV in the children was microscopic polyarteritis with wide-spread glomerular crescents formation and capillary tuft fibrinoid necrosis. Variety of complement C3 deposits and weak immunoglobulin deposits were noted in all ASV but one child who showed relatively strong deposits of IgA and IgM. The electronic dense deposits were mainly located in subendothelial space but were also found in the glomerular basement membrane in one child. (4) Three children with ASV died within one year after diagnosis, and two got remission and restored renal function after combined pulse therapy with methylprednisolone and cyclophosphamide (CTX), but remained to have hematuria and small amount of proteinuria after 1 and 5 year follow-up, respectively. CONCLUSION: Childhood ASV was female and P-ANCA predominant, more vulnerable to progress to renal failure and poorer in prognosis than adult cases. Qualitative and quantitative ANCA measurement and renal biopsy were key to the diagnosis of ASV in children.