免疫球蛋白G4在炎症性肠病中的表达及其临床意义

Expression and its clinical significance of immunoglobulin G4 in inflammatory bowel disease

目的通过检测IBD患者血清和肠黏膜组织中免疫球蛋白G4（IgG4）的表达水平，探讨IgG4在IBD患者中的表达特征及其临床意义。方法收集2015年3月至2016年8月就诊的68例UC患者和132例CD患者，另选取52名健康对照者。采用免疫散射比浊法检测血清IgG4水平，免疫组织化学法分析IgG4在肠黏膜中的原位表达，每个样本随机取5个高倍镜视野（HPF）。检测UC、CD患者和健康对照者CRP和ESR，同时评估疾病活动范围、临床类型、活动指数EUC采用Mayo评分，CD采用克罗恩病活动指数（CDAI）]和目前的治疗药物。分析IgG4表达水平与CRP、ESR、Mayo评分和CDAI的相关性。采用独立样本t检验、卡方检验和Pearson相关性分析对结果进行分析。结果免疫散射比浊法结果显示，UC、CD患者和健康对照组血清IgG4水平分别为（0．79±0．61）、（O．69±0．59）、（O．41±0．32）g／L，均低于血清IgG4标准值1．35g／L。免疫组织化学结果显示，活动期UC和活动期CD患者肠黏膜IgG4阳性细胞数均高于健康对照组[分别为（15．42±12．47）／HPF、（18．65±12．46）／HPF、（4．71±4．14）／HPF]，差异有统计学意义（t=5．392、8．450，P均d0．05）；缓解期UC和缓解期CD患者肠黏膜IgG4表达水平与健康对照组比较[分别为（4．72±4．23）／HPF、（5．30±4．87）／HPF、（4．71±4．14）／HPF]，差异均无统计学意义（P均〉O．05），活动期UC和缓解期UC肠黏膜IgG4表达水平分别与活动期CD和缓解期CD比较差异均无统计学意义（P均〉0．05）。IgG4阳性UC患者活动期例数、CRP、ESR和Mayo评分均高于IgG4阴性组（x2=5．499，F2．811、3．471、4．676；P均d0．05）；IgG4阳性CD患者活动期例数、CRP、ESR和CDAI均高于IgG4阴性组（x2=4．341，产3．842、3．892、2．935；P均〈0．05）。UC患者IgG4阳性浆细胞浸润数与CRP、ESR、Mayo评分均呈正相关（r=0．382、0．381、0．470，P=0．001、0．003、P〈O．01）。CD患者IgG4阳性浆细胞浸润数与CRP、ESR、CDAI均呈正相关（r=0．199、0．209、0．201，P=0．022、0．016、0．021）。结论IgG4水平在活动期IBD患者肠黏膜中表达显著增高，其表达与疾病活动度明显相关，IgG4表达水平可作为评价IBD病情活动度的指标之一。

Objective To explore the expression and its clinical significance of immunoglobulin G4 （IgG4） in inflammatory bowel disease （IBD） by detecting the expression of IgG4 in the serum and intestinal mucosa of patients with IBD. Methods From March 2015 to August 2016, 68 patients with ulcerative colitis （UC）, 132 patients with Crohn＇s disease （CD） and 52 healthy controls were collected. The serum levels of IgG4 were detected by immunonephelometry. The expression of IgG4 in intestinal mucosa was analyzed by immunohistochemistry. Five high power fields （HPF） were randomly selected in each specimen. C-reaction protein （CRP） and erythrocyte sedimentation rate （ESR） of patients with UC, patients with CD and healthy controls were detected. The extent of disease, clinical type, disease activity scores （UC scored by Mayo score system, CD scored by Crohn±s disease activity index （CDAI）） and current treatment were collected. The correlation between IgG4 expression and CRP, ESR, Mayo scoreand CDAI were analyzed. Independent sample t test, Chi square test and Pearson＇s correlation were performed for statistical analysis. Results The results of immunonephelometry indicated that the serum levels of IgG4 of patients with UC, CD and healthy controls were （0.79 ± 0.61 ）, （0.69 ± 0.59） and （0.41 ± 0. 32） g/L, respectively; all were lower than standard level 1. 35 g/L. The results of immunohistochemistry revealed that the number of IgG4 positive cells in the colonic mucosa of active UC and CD patients were higher than that of healthy controls （（15.42±12.47）/HPF, （18.65±12.46）/HPF and （4.71±4. 14）/ HPF）, and the differences were statistically significant （t = 5. 392 and 8. 450, both P〈0.05）. There was no statistically significant difference in mueosal IgG4 expression between UC, CD patients at remission phase and healthy controls （（4.72±4.23）/HPF, （5.30±4.87）/HPF and （4.71±4.14）/HPF,both P〉 0.05）. There was no statistically significant difference in mucosal IgG4 expression between UC and CD patients at active phase and remission phase （both P〈0.05）. The case number of active patients, CRP, ESR and Mayo scores of IgG4 positive UC patients were all higher than those of IgG4 negative group（;（2 = 5.499,t=2. 811, 3. 471 and 4. 676; all P〈0.05）. The number of active patients, CRP, ESR and CDAI of IgG4 positive CD patients were all higher than those of IgG4 negative group（z2 = 4. 341, t = 3. 842, 3. 892 and 2. 935, all P〈 0. 05）. In UC patients, the number of IgG4 positive cells was positively correlated with CRP, ESR and Mayo scores （r=0. 382, 0. 381 and 0. 470; P= 0. 001, 0. 003 and P〈 0.01）. The number of IgG4 positive cells was positively correlated with CRP, ESR and CDAI in CD patients （r=0. 199, 0. 209 and 0. 201; P=0. 022, 0. 016 and 0. 021）. Conclusions The expression level of IgG4 significantly increased in the intestinal mucosa of IBD patients correlated with the activity of disease. The expression level of IgG4 may be one of the parameters to evaluate the activity of IBD.