过敏性紫癜患儿血清中IgA1半乳糖基的缺失水平及临床意义
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摘要
目的探讨过敏性紫癜((Henoch-Schnlein purpura,HSP)患儿血清IgA1半乳糖基的缺失水平与其临床特点的相关性,以指导临床个体化治疗。方法根据临床症状和疗效将57例HSP患儿分为:非紫癜肾普通组(26例),包括已激素治疗(12例)和尚未激素治疗者(14例);HSP肾病组(7例);难治性HSP组(7例);治愈组(17例)。另选健康体检儿童24例作为对照值。以凝集素(lectin)亲和ELISA法及IgA1抗体亲和ELISA法分别检测HSP患儿和对照组血清IgA1半乳糖基的缺失水平及IgA1水平。结果 57例HSP患儿中,40例未治愈者的血清IgA1半乳糖基缺失水平均高于治愈组和对照组,差异有统计学意义(P均<0.05);而治愈组与对照组间的差异无统计学意义(P>0.05)。在HSP的各亚组中,HSP肾病组、非紫癜肾普通组和难治性HSP组的血清IgA1半乳糖基缺失水平均高于对照组;难治性HSP组高于非紫癜肾普通组,差异有统计学意义(P均<0.05)。HSP肾病组与难治性HSP组及与非紫癜肾普通组患儿间血清IgA1半乳糖基缺失水平的差异无统计学意义(P均>0.05)。非紫癜肾普通组中,尚未激素治疗组血清IgA1半乳糖基缺失水平高于已予激素治疗组,差异有统计学意义(P<0.05)。结论 IgA1半乳糖基的缺失水平可以客观反映HSP的疾病活动状况和疗效预期,尤其对于难治性HSP患儿,有望成为临床有效的生物监测靶标以决策和指导糖皮质激素以及免疫抑制剂在HSP患儿中的合理使用。
Objective To explore the association of galactose-deficient IgA1 levels with clinical features, and further to provide guidance for individualized treatment of HSP. Methods According to the clinical symptoms and curative effect, 57 children with HSP were divided into four groups: non-HSPN group(n=26), HSPN group(n=7), refractory HSP group(n=7) and remission group(n=17). In non-HSPN group, 12 cases received glucorticoid therapy and 14 cases did not. Serum galactose-deficient IgA1(Gd-IgA1) concentrations were detected using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay(ELISA), and the total IgA1 levels were measured by ELISA. Results The serum Gd-IgA1 level was significantly higher in 40 HSP children who were not cured than that in remission group and control group(P<0.05). However, there was no difference in Gd-IgA1 level between remission group and control group(P>0.05). Compared with the control group, the serum Gd-IgA1 level was significantly higher in HSPN group, non-HSPN group and refractory HSP, and children with refractory HSP had significantly higher Gd-IgA1 level than children in non-HSPN group(P<0.05). No significant difference in Gd-IgA1 level was found either between HSPN group and refractory HSP group or between HSPN group and non-HSPN group(P>0.05). Furthermore, in nonHSPN group, the serum Gd-IgA1 level in HSP children who were not treated with glucorticoid was significantly higher than that in HSP children treated with glucorticoid(P<0.05). Conclusions The serum Gd-IgA1 level is associated with the disease activity and curative effect of HSP, especially in children with refractory HSP, and it is thus likely to be a new non-invasive disease activity marker for guiding the proper usage of glucocorticoid and immunosuppressants in HSP children.
Objective To explore the association of galactose-deficient IgA1 levels with clinical features, and further to provide guidance for individualized treatment of HSP. Methods According to the clinical symptoms and curative effect, 57 children with HSP were divided into four groups: non-HSPN group(n=26), HSPN group(n=7), refractory HSP group(n=7) and remission group(n=17). In non-HSPN group, 12 cases received glucorticoid therapy and 14 cases did not. Serum galactose-deficient IgA1(Gd-IgA1) concentrations were detected using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay(ELISA), and the total IgA1 levels were measured by ELISA. Results The serum Gd-IgA1 level was significantly higher in 40 HSP children who were not cured than that in remission group and control group(P<0.05). However, there was no difference in Gd-IgA1 level between remission group and control group(P>0.05). Compared with the control group, the serum Gd-IgA1 level was significantly higher in HSPN group, non-HSPN group and refractory HSP, and children with refractory HSP had significantly higher Gd-IgA1 level than children in non-HSPN group(P<0.05). No significant difference in Gd-IgA1 level was found either between HSPN group and refractory HSP group or between HSPN group and non-HSPN group(P>0.05). Furthermore, in nonHSPN group, the serum Gd-IgA1 level in HSP children who were not treated with glucorticoid was significantly higher than that in HSP children treated with glucorticoid(P<0.05). Conclusions The serum Gd-IgA1 level is associated with the disease activity and curative effect of HSP, especially in children with refractory HSP, and it is thus likely to be a new non-invasive disease activity marker for guiding the proper usage of glucocorticoid and immunosuppressants in HSP children.
引文
[1]Gardner-Medwin JM,Dolezalova P,Cummins C,et al.Incidence of Henoch-Schnlein purpura,Kawasaki disease,and rare vasculitides in children of different ethnic origins[J].Lancet,2002,360(9341):1197-1202.
[2]Saulsbury FT.Henoch-Schnlein purpura[J].Curr Opin Rheumatol,2010,22(5):598-602.
[3]Narchi H.Risk of long term renal impairment and duration of follow up recommended for Henoch-Schnlein purpura with normal or minimal urinary findings:a systematic review[J].Arch Dis Child,2005,90(9):916-920.
[4]Jauhola O,Ronkainen J,Koskimies O,et al.Renal manifestations of Henoch-Schnlein purpura in a 6-month prospective study of 223 children[J].Arch Dis Child,2010,95(11):877-882.
[5]Kawasaki Y,Ono A,Ohara S,et al.Henoch-Schnlein purpura nephritis in childhood:pathogenesis,prognostic factors and treatment[J].Fukushima J Med Sci,2013,59(1):15-26.
[6]吴歌,权松霞,张茜,等.紫癜性肾炎的临床病理及治疗方法分析[J].中日友好医学报,2013,27(6):338-345.
[7]Bogdanovi R.Henoch-Schnlein purpura nephritis in children:risk factors,prevention and treatment[J].Acta Paediatr,2009,98(12):1882-1889.
[8]Donnithorne KJ,Atkinson TP,Hinze CH,et al.Rituximab therapy for severe refractory chronic Henoch-Schnlein purpura[J].J Pediatr,2009,155(1):136-139.
[9]Huang DC,Yang YH,Lin YT,et al.Cyclosporin A therapy for steroid-dependent Henoch-Schnlein purpura[J].J Microbiol Immunol Infect,2003,36(1):61-64.
[10]Kawasaki Y,Ono A,Ohara S,et al.Henoch-Schnlein purpura nephritis in childhood:pathogenesis,prognostic factors and treatment[J].Fukushima J Med Sci,2013,59(1):15-26.
[11]Lau KK,Wyatt RJ,Moldoveanu Z,et al.Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schnlein purpura[J].Pediatr Nephrol,2007,22(12):2067-2072.
[12]Suzuki H,Fan R,Zhang Z,et al.Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity[J].J Clin Invest,2009,119(6):1668-1677.
[13]Allen AC,Bailey EM,Brenchley PE,et al.Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation:observations in three patients[J].Kidney Int,2001,60(3):969-973.
[14]中华医学会儿科学分会免疫学组.儿童过敏性紫癜循证诊治建议(2013)[J].中华儿科杂志,2013,51(7):502-506.
[15]中华医学会儿科学分会肾病学组.儿童常见肾脏疾病诊治循证指南紫癜性肾炎的诊治循证指南[J].中华儿科杂志,2009,47(12):911-913.
[16]Berthelot L,Papista C,Maciel TT,et al.Transglutaminase is essential for IgA nephropathy development acting through IgA receptors[J].J Exp Med,2012,209(4):793-806.
[17]Tamouza H,Chemouny JM,Raskova Kafkova L,et al.The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy[J].Kidney Int,2012,82(12):1284-1296.
[18]Yoo EM,Morrison SL.IgA:an immune glycoprotein[J].Clin Immunol,2005,116(1):3-10.
[19]刘云,徐汉云.过敏性紫癜患儿IgA1异常糖基化水平的意义[J].南昌大学学报:医学版,2013,53(2):66-68.
[20]金燕樑,周纬,徐亚珍,等.儿童过敏性紫癜与T-细胞亚群研究[J].临床儿科杂志,2006,24(9):754-755.
[21]Tizard EJ.Henoch-Schnle inpurpura[J].Arch Dis Child,1999,80(4):380-383.
[2]Saulsbury FT.Henoch-Schnlein purpura[J].Curr Opin Rheumatol,2010,22(5):598-602.
[3]Narchi H.Risk of long term renal impairment and duration of follow up recommended for Henoch-Schnlein purpura with normal or minimal urinary findings:a systematic review[J].Arch Dis Child,2005,90(9):916-920.
[4]Jauhola O,Ronkainen J,Koskimies O,et al.Renal manifestations of Henoch-Schnlein purpura in a 6-month prospective study of 223 children[J].Arch Dis Child,2010,95(11):877-882.
[5]Kawasaki Y,Ono A,Ohara S,et al.Henoch-Schnlein purpura nephritis in childhood:pathogenesis,prognostic factors and treatment[J].Fukushima J Med Sci,2013,59(1):15-26.
[6]吴歌,权松霞,张茜,等.紫癜性肾炎的临床病理及治疗方法分析[J].中日友好医学报,2013,27(6):338-345.
[7]Bogdanovi R.Henoch-Schnlein purpura nephritis in children:risk factors,prevention and treatment[J].Acta Paediatr,2009,98(12):1882-1889.
[8]Donnithorne KJ,Atkinson TP,Hinze CH,et al.Rituximab therapy for severe refractory chronic Henoch-Schnlein purpura[J].J Pediatr,2009,155(1):136-139.
[9]Huang DC,Yang YH,Lin YT,et al.Cyclosporin A therapy for steroid-dependent Henoch-Schnlein purpura[J].J Microbiol Immunol Infect,2003,36(1):61-64.
[10]Kawasaki Y,Ono A,Ohara S,et al.Henoch-Schnlein purpura nephritis in childhood:pathogenesis,prognostic factors and treatment[J].Fukushima J Med Sci,2013,59(1):15-26.
[11]Lau KK,Wyatt RJ,Moldoveanu Z,et al.Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schnlein purpura[J].Pediatr Nephrol,2007,22(12):2067-2072.
[12]Suzuki H,Fan R,Zhang Z,et al.Aberrantly glycosylated IgA1 in IgA nephropathy patients is recognized by IgG antibodies with restricted heterogeneity[J].J Clin Invest,2009,119(6):1668-1677.
[13]Allen AC,Bailey EM,Brenchley PE,et al.Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation:observations in three patients[J].Kidney Int,2001,60(3):969-973.
[14]中华医学会儿科学分会免疫学组.儿童过敏性紫癜循证诊治建议(2013)[J].中华儿科杂志,2013,51(7):502-506.
[15]中华医学会儿科学分会肾病学组.儿童常见肾脏疾病诊治循证指南紫癜性肾炎的诊治循证指南[J].中华儿科杂志,2009,47(12):911-913.
[16]Berthelot L,Papista C,Maciel TT,et al.Transglutaminase is essential for IgA nephropathy development acting through IgA receptors[J].J Exp Med,2012,209(4):793-806.
[17]Tamouza H,Chemouny JM,Raskova Kafkova L,et al.The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy[J].Kidney Int,2012,82(12):1284-1296.
[18]Yoo EM,Morrison SL.IgA:an immune glycoprotein[J].Clin Immunol,2005,116(1):3-10.
[19]刘云,徐汉云.过敏性紫癜患儿IgA1异常糖基化水平的意义[J].南昌大学学报:医学版,2013,53(2):66-68.
[20]金燕樑,周纬,徐亚珍,等.儿童过敏性紫癜与T-细胞亚群研究[J].临床儿科杂志,2006,24(9):754-755.
[21]Tizard EJ.Henoch-Schnle inpurpura[J].Arch Dis Child,1999,80(4):380-383.