血清IgG及IgG4检测在ANCA相关性血管炎中的诊断价值
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摘要
目的研究分析血清IgG及IgG4在ANCA相关性血管炎(AAV)患者中的表达,探讨IgG4在AAV中的诊断价值。方法收集本院就诊的AAV患者血清48例为患者组,同期健康人血清25例作为对照组,用ELISA法检测IgG4浓度,免疫比浊法检测IgG浓度,船式ELISA法检测抗髓过氧化物酶抗体(anti-MPO)和抗蛋白酶3抗体(anti-PR3)浓度,两组数据间比较用t检验,多组数据用单因素方差分析,两两间比较用LSD-t检验,两组间指标相关性分析用Pearson相关性分析,以P<0.05为差异有统计学意义。结果 AAV患者组血清IgG4浓度为(1.17±0.58)g/L,IgG4/IgG为(10.12±6.64)%,明显高于健康对照组,差异有统计学意义(P<0.01);MPO-ANCA相关性AAV和PR3-ANCA相关性AAV患者组的血清IgG4浓度及IgG4/IgG较健康对照组均有明显升高(P<0.01),但两个亚型之间的IgG4表达没有差异(P>0.05),ANCA浓度与IgG4浓度也没有明显相关性(P>0.05)。结论 AAV或其亚型患者的IgG4浓度及IgG4/IgG均有明显升高,但与ANCA的类型及其浓度没有明显相关性,IgG4联合ANCA检查有助于AAV的诊断。
Objective To investigate the expression of serum IgG and IgG4 in the patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), and explore the diagnostic value of IgG4 in AAV patients. Methods A total of 48 patients with AAV admitted in our hospital from July 2016 to June 2018 were recruited as patient group, and 25 healthy persons during the same period were subjected as control group. Their serum samples were collected for concentration of IgG4 by ELISA, that of IgG by immunoturbidimetric assay, and those of anti-MPO and anti-PR3 antibodies by ship type ELISA. Student's t test was used to make data comparison between the 2 groups, one-way ANOVA was employed for comparison among the multiple groups, and LSD-t test was applied for intragroup comparison. Pearson correlation analysis was used to analyze the correlation between the 2 groups, and P<0.05 was considered statistically. Results The serum IgG4 concentration was 1.17±0.58 g/L, and the percentage of IgG4 to IgG was(10.12±6.64)% in the AAV patients, which were significantly higher than those of healthy individuals(P<0.01). So were the concentrations in the MPO-ANCA-associated and PR3-ANCA-associated AAV patients(P<0.01). But there was no difference in the expression of IgG4 between the 2 subtypes(P>0.05), and there was no significant correlation between ANCA concentration and IgG4 concentration(P>0.05). Conclusion IgG4 concentration and IgG4/IgG percentage are significantly increased in the patients with AAV or its subtypes. But there is no significant correlation with the types and ANCA concentration. Detection of IgG4 combined with ANCA is helpful in the diagnosis of AAV.
Objective To investigate the expression of serum IgG and IgG4 in the patients with antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis(AAV), and explore the diagnostic value of IgG4 in AAV patients. Methods A total of 48 patients with AAV admitted in our hospital from July 2016 to June 2018 were recruited as patient group, and 25 healthy persons during the same period were subjected as control group. Their serum samples were collected for concentration of IgG4 by ELISA, that of IgG by immunoturbidimetric assay, and those of anti-MPO and anti-PR3 antibodies by ship type ELISA. Student's t test was used to make data comparison between the 2 groups, one-way ANOVA was employed for comparison among the multiple groups, and LSD-t test was applied for intragroup comparison. Pearson correlation analysis was used to analyze the correlation between the 2 groups, and P<0.05 was considered statistically. Results The serum IgG4 concentration was 1.17±0.58 g/L, and the percentage of IgG4 to IgG was(10.12±6.64)% in the AAV patients, which were significantly higher than those of healthy individuals(P<0.01). So were the concentrations in the MPO-ANCA-associated and PR3-ANCA-associated AAV patients(P<0.01). But there was no difference in the expression of IgG4 between the 2 subtypes(P>0.05), and there was no significant correlation between ANCA concentration and IgG4 concentration(P>0.05). Conclusion IgG4 concentration and IgG4/IgG percentage are significantly increased in the patients with AAV or its subtypes. But there is no significant correlation with the types and ANCA concentration. Detection of IgG4 combined with ANCA is helpful in the diagnosis of AAV.
引文
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[16] CARBONE G,WILSON A,DIEHL S A,et al.Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis[J].Int J Biol Sci,2013,9(3):279-288.DOI:10.7150/ijbs.5996.
[17] ZAIDAN M,CERVERA-PIEROT P,DE SEIGNEUX S,et al.Evidence of follicular T-cell implication in a case of IgG4-related systemic disease with interstitial nephritis[J].Nephrol Dial Transplant,2011,26(6):2047-2050.DOI:10.1093/ndt/gfr097.
[18] TANGYE S G,LIU Y J,AVERSA G,et al.Identification of functional human splenic memory B cells by expression of CD148 and CD27[J].J Exp Med,1998,188(9):1691-1703.
[2] UMEHARA H,OKAZAKI K,MASAKI Y,et al.Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD),2011[J].Mod Rheumatol,2012,22(1):21-30.DOI:10.1007/s10165-011-0571-z.
[3] 高辉,张萍,李贵森,等.ANCA相关性肾炎合并IgG4相关性疾病一例[J].中华肾脏病杂志,2014(12):953-954.DOI:10.3760/cma.j.issn.1001-7097.2014.12.014.GAO H,ZHANG P,LI G S,et al.A case report of ANCA-associated nephritis with IgG4-related diseases [J].Chin J Nephrol,2014(12):953-954.DOI:10.3760/cma.j.issn.1001-7097.2014.12.014.
[4] IGUCHI A,WADA Y,KOBAYASHI D,et al.A case of MPO- and PR3-ANCA-positive hypertrophic cranial pachymeningitis with elevated serum IgG4[J].Mod Rheumatol,2013,23(1):151-155.DOI:10.1007/s10165-012-0613-1.
[5] JENNETTE J C.Overview of the 2012 revised international chapel hill consensus conference nomenclature of vasculitides[J].Clin Exp Nephrol,2013,17(5):603-606.DOI:10.1007/s10157-013-0869-6.
[6] CORNEC D,CORNEC-LE GALL E,FERVENZA F C,et al.ANCA-associated vasculitis-clinical utility of using ANCA specificity to classify patients[J].Nat Rev Rheumatol,2016,12(10):570-579.DOI:10.1038/nrrheum.2016.123.
[7] DANLOS F X,ROSSI G M,BLOCKMANS D,et al.Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease:A new overlap syndrome[J].Autoimmun Rev,2017,16(10):1036-1043.DOI:10.1016/j.autrev.2017.07.020.
[8] LI Z Y,MA T T,CHEN M,et al.The prevalence and management of anti-neutrophil cytoplasmic antibody-associated vasculitis in China[J].Kidney Dis (Basel),2016,1(4):216-223.DOI:10.1159/000441912.
[9] SAKAIRI T,OKABE S,HIROMURA K,et al.A case of ANCA-negative renal small-vessel vasculitis with tubulointerstitial infiltration of IgG4-positive plasma cells[J].Mod Rheumatol,2016,26(5):780-783.DOI:10.3109/14397595.2014.915510.
[10] 于峰,赵明辉,章友康.原发性小血管炎中ANCA IgG亚型的分布及临床意义[J].中华微生物学和免疫学杂志,2003,23(9):747-748.DOI:10.3760/j:issn:0254-5101.2003.09.028.YU F,ZHAO M H,ZHANG Y K.Distribution and clinical significance of ANCA IgG subtypes in primary vasculitis [J].Chin J Microbiol Immunol,2003,23(9):747-748.DOI:10.3760/j:issn:0254-5101.2003.09.028.
[11] KANARI H,KAGAMI S,KASHIWAKUMA D,et al.Role of Th2 cells in IgG4-related lacrimal gland enlargement[J].Int Arch Allergy Immunol,2010,152(Suppl 1):47-53.DOI:10.1159/000312125.
[12] SUZUKI K,TAMARU J,OKUYAMA A,et al.IgG4-positive multi-organ lymphoproliferative syndrome manifesting as chronic symmetrical sclerosing dacryo-sialadenitis with subsequent secondary portal hypertension and remarkable IgG4-linked IL-4 elevation[J].Rheumatology (Oxford),2010,49(9):1789-1791.DOI:10.1093/rheumatology/keq113.
[13] TIPPING P G,KITCHING A R.Glomerulonephritis,Th1 and Th2:what’s new?[J].Clin Exp Immunol,2005,142(2):207-215.DOI:10.1111/j.1365-2249.2005.02842.x.
[14] SPIEGELBERG H L.Fc receptors for IgE and interleukin-4 induced IgE and IgG4 secretion[J].J Invest Dermatol,1990,94(6):s49-s52.DOI:10.1111/1523-1747.ep12875051.
[15] KUROKI A,IYODA M,SHIBATA T,et al.Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic membranous nephropathy[J].Kidney Int,2005,68(1):302-310.DOI:10.1111/j.1523-1755.2005.00415.x.
[16] CARBONE G,WILSON A,DIEHL S A,et al.Interleukin-6 receptor blockade selectively reduces IL-21 production by CD4 T cells and IgG4 autoantibodies in rheumatoid arthritis[J].Int J Biol Sci,2013,9(3):279-288.DOI:10.7150/ijbs.5996.
[17] ZAIDAN M,CERVERA-PIEROT P,DE SEIGNEUX S,et al.Evidence of follicular T-cell implication in a case of IgG4-related systemic disease with interstitial nephritis[J].Nephrol Dial Transplant,2011,26(6):2047-2050.DOI:10.1093/ndt/gfr097.
[18] TANGYE S G,LIU Y J,AVERSA G,et al.Identification of functional human splenic memory B cells by expression of CD148 and CD27[J].J Exp Med,1998,188(9):1691-1703.