CD20阳性细胞和HLA-DR表达对移植肾急性排斥反应预后判断的价值

Evaluation of CD20 cell infiltration and HLA-DR express on outcome of renal graft in patients with acute rejection

目的:探讨CD20阳性细胞在移植肾细胞性排斥反应中浸润程度与预后的关系及其在移植物中的作用。方法:2001年至2002年共29例经移植肾活检诊断为细胞性和混合性移植肾急性排斥患者,肾活检组织标本行CD20、人白细胞DR抗原(HLA-DR)免疫组化染色,C4d免疫荧光染色。并对病理结果行半定量分析,根据CD20细胞在肾组织内浸润程度,分为重度浸润组(H组,>50%小管间质面积),中度浸润组(M组,10%～50%),阴性组(N组,<10%),C4d染色按照Banff标准分为阳性组和阴性组,HLA-DR染色分为阳性(>50%)和阴性(<50%)组。分别分析CD20和排斥反应分型、HLA-DR、C4d之间的相关性。所有病例均随访42月,随访内容包括患者急性排斥反应临床资料和治疗反应情况,随访期间肌酐变化和移植肾的预后。结果:29例患者中H组有6例,M组7例,N组16例。H组耐激素发生率高于另外两组(4/6vs2/7vs2/16,P=0.05)。42月时H组移植肾生存率明显低于另外两组(4/6vs1/7vs1/16,P<0.05),M组平均血肌酐高于N组(208.6μmol/Lvs112.3μmol/L,P<0.01)。CD20阳性(H+M组)和C4d染色阳性之间没有一致性(P>0.05)。而H+M组HLA-DR表达明显高于N组(59.5%vs16.3%,P<0.01);HLA-DR阳性与CD20阳性具有很好的一致性(P<0.01)。结论:CD20阳性细胞在肾移植急性排斥反应内浸润的程度与移植肾短期和长期预后有明显相关性。CD20细胞的浸润与体液性排斥反应无明显相关性,但是和肾组织中HLA-DR有一定的相关性,提示CD20细胞在移植物内不产生抗体,推测可能与抗原呈递有关,有待进一步研究。

Objective：CD20 was a B cell marker. It has been report that CD20 positive cell infiltration in the acute cellular rejection of renal allograft had poorer outcome. However, it is unknown whether the degree of B cell infiltration is correlated with different outcome, and what role the B cell infiltration may play in the allograft. Methodology：The histology of 29 cases with renal allograft acute rejection from 2001 to 2002 was retrospectively analyzed. CD20, HLA-DR was assayed by immunochemistry staining and was semiquantitative analyzed. C4d staining was also assayed in all cases. These cases were divided into three groups according to the degree of CD20 positive cell infiltration with semiquantitative method： severe group （ ≥50% area n =6）, moderate infiltration （≥10%, 〈50% area n =7） and negative group （ 〈 10% area n = 16）. All cases were followed at least 42 months to collect information of treatment, serum creatinine （SCr） and graft survival. Results：Steroids resistant ratio was different among three groups（4/6 severe vs 2/7 moderate vs 2/16 negative, P = 0. 05 ）. In the 42nd month of the following-up, the graft loss ratio of severe group was higher than that of moderate and negative group （4/6 vs 1/7 vs 1/16, P 〈0. 05） ; the average SCr of moderate group was higher than that of negative group （208. 6 μmol/L vs 112. 3 μmol/L,P 〈0. 01 ）. CD20 positive cases has no accordance with CAd positive （P = 0. 666）. HLA-DR expressing on the allograft tubule of CD20 positive group was higher than that of CD20 negative group （59. 5% vs 16. 3%, P 〈 0. 01 ）, and HLA-DR express ≥50% was significantly correlative with CD20 positive （P 〈 0. 01 ）. Conclusion：The degree of CD20 positive cell infiltration in the renal acute rejection allograft was a poor prognostic factor for short and long-term allograft outcome. CD20 positive cell has no concordance with antibody generation, but has concordance with HLA-DR express in the allograft, which suggests that B cell be associated with antigen presentation.