Dasgupta A, Mandal A, Das K M
Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903.
Gut. 1994 Dec;35(12):1712-7. doi: 10.1136/gut.35.12.1712.
Autoimmunity has been implicated in the pathogenesis of ulcerative colitis (UC). Several studies have shown amplified immunoglobulin G1 (IgG1) antibody response in UC; however the immunoreactive antigen(s) is unknown. To study this antigen(s), mucosal colonic extract was prepared by sonication, ultracentrifugation followed by ion exchange chromatography in fast protein liquid chromatography. The fraction (enriched colonic peptide), that was most reactive to a novel monoclonal antibody, 7E12H12 (IgM isotype), was isolated and used to examine the immunoreactivity against the patients' serum samples. Two hundred and thirteen coded samples from 111 patients with UC (symptomatic and untreated (63), symptomatic and treated (26), remission (22)); 47 with Crohn's disease (CD) (40 were symptomatic and untreated, and 30 had colonic disease); 29 with acute diarrhoea caused by specific pathogen(s); 10 with systemic lupus erythematosus, and 16 normal subjects were examined against the enriched colonic peptide by IgG subtype specific enzyme linked immunosorbent assays (ELISAs). Total IgG antibody reactivity was significantly (p < 0.01) higher only in symptomatic and untreated UC patients compared with each of the non-UC group, but the sensitivity was only 50%. IgG2 and IgG3 reactivities were not different among various groups. The IgG1 antibody reactivity against the enriched colonic peptide, however, differentiated UC patients from CD and each of the other non-UC groups. Seventy nine per cent of the patients with UC, treated or untreated, symptomatic or in remission, had significantly (p < 0.0001) higher IgG1 antibody against the enriched colonic peptide when compared with each of the other non-UC groups. Only 12% of CD serum samples and none of the other control serum samples reacted. Using purified serum IgG1 and 7E12H12-IgM, by 7E12H12 reactive peptide indeed reacts with UC-IgG1 antibody but not with control IgG1.
自身免疫被认为与溃疡性结肠炎（UC）的发病机制有关。多项研究表明，UC患者体内免疫球蛋白G1（IgG1）抗体反应增强；然而，免疫反应性抗原尚不清楚。为了研究这种抗原，通过超声处理、超速离心，然后在快速蛋白质液相色谱中进行离子交换色谱法制备结肠黏膜提取物。分离出对新型单克隆抗体7E12H12（IgM亚型）反应最强的部分（富含结肠肽），并用于检测其与患者血清样本的免疫反应性。采用IgG亚型特异性酶联免疫吸附测定（ELISA），对111例UC患者（有症状且未治疗的63例、有症状且已治疗的26例、缓解期的22例）、47例克罗恩病（CD）患者（40例有症状且未治疗，30例有结肠疾病）、29例由特定病原体引起的急性腹泻患者、10例系统性红斑狼疮患者以及16例正常受试者的213份编码样本进行了针对富含结肠肽的检测。仅在有症状且未治疗的UC患者中发现，其总IgG抗体反应性与各非UC组相比显著更高（p < 0.01），但敏感性仅为50%。IgG2和IgG3反应性在不同组之间无差异。然而，针对富含结肠肽的IgG1抗体反应性可将UC患者与CD患者及其他非UC组区分开来。与其他非UC组相比，79%的UC患者（无论治疗与否、有症状或处于缓解期）针对富含结肠肽的IgG1抗体显著更高（p < 0.0001）。只有12%的CD血清样本有反应，其他对照血清样本均无反应。使用纯化的血清IgG1和7E12H12-IgM，发现7E12H12反应性肽确实与UC-IgG1抗体反应，但不与对照IgG1反应。
