Cellier C, Delabesse E, Helmer C, Patey N, Matuchansky C, Jabri B, Macintyre E, Cerf-Bensussan N, Brousse N
Department of Gastroenterology, Hôpital Laennec, INSERM E9925, Paris, France.
Lancet. 2000 Jul 15;356(9225):203-8. doi: 10.1016/s0140-6736(00)02481-8.
Adult refractory sprue is a poorly defined disorder. We did a multicentre national study of patients with refractory sprue to characterise their clinical and pathological profile and outcome, and to assess the frequency and prognostic significance of phenotypic and molecular abnormalities in the intraepithelial T-cell population.
Patients with severe symptomatic villous atrophy mimicking coeliac disease but refractory to a strict gluten-free diet, and with no initial evidence of overt lymphoma, were diagnosed at gastrointestinal referral centres between 1974 and 1998. Fixed and/or frozen duodenojejunal biopsy samples were reanalysed and immunostained with CD3 and CD8 monoclonal antibodies to find out the phenotype of intraepithelial lymphocytes (IEL). TCRgamma gene rearrangements were assessed on frozen biopsy samples by multiplex fluorescent PCR.
There were 21 patients with refractory sprue and 20 controls with coeliacs disease. 16 (84%) of 19 assessed patients had an aberrant intraepithelial lymphoid intestinal population expressing intracytoplasmic CD3 but not surface CD8. Clonal intestinal TCRgamma gene rearrangements were found in 13 (76%) of 17 patients assessed; four (out of 12 assessed) had clonal dissemination to the blood. The 16 patients with an aberrant phenotype all had uncontrolled malabsorption; three subsequently developed overt T-cell lymphoma, and eight died. The three (16%) patients without aberrant clonal IEL made a complete clinical and histological recovery with steroid therapy plus a gluten-free diet.
An immunophenotypically aberrant clonal intraepithelial T-cell population (similar to that of most cases of enteropathy-associated T-cell lymphoma) can be found in up to 75% of patients with refractory coeliac sprue; its identification by simple diagnostic techniques represents a marker of poor outcome (including occurrence of overt T-cell lymphoma). We suggest that refractory sprue associated with an aberrant clonal IEL may be the missing link between coeliac disease and T-cell lymphoma and may be classified as cryptic enteropathy-associated T-cell lymphoma.
成人难治性口炎性腹泻是一种定义不明确的疾病。我们对难治性口炎性腹泻患者进行了一项全国性多中心研究，以描述其临床和病理特征及预后，并评估上皮内T细胞群体中表型和分子异常的频率及预后意义。
1974年至1998年间，在胃肠转诊中心诊断出患有严重症状性绒毛萎缩，类似乳糜泻但对严格无麸质饮食难治，且最初无明显淋巴瘤证据的患者。对固定和/或冷冻的十二指肠空肠活检样本进行重新分析，并用CD3和CD8单克隆抗体进行免疫染色，以确定上皮内淋巴细胞（IEL）的表型。通过多重荧光PCR对冷冻活检样本评估TCRγ基因重排。
有21例难治性口炎性腹泻患者和20例乳糜泻对照患者。19例评估患者中有16例（84%）上皮内淋巴样肠道群体异常，表达胞浆内CD3但不表达表面CD8。17例评估患者中有13例（76%）发现克隆性肠道TCRγ基因重排；12例评估患者中有4例克隆播散至血液。16例表型异常的患者均有未控制的吸收不良；3例随后发展为明显的T细胞淋巴瘤，8例死亡。3例（16%）无异常克隆IEL的患者经类固醇治疗加无麸质饮食后临床和组织学完全恢复。
高达75%的难治性乳糜泻口炎性腹泻患者可发现免疫表型异常的克隆性上皮内T细胞群体（类似于大多数肠病相关T细胞淋巴瘤病例）；通过简单诊断技术对其进行识别是预后不良（包括发生明显T细胞淋巴瘤）的标志物。我们认为，与异常克隆IEL相关的难治性口炎性腹泻可能是乳糜泻和T细胞淋巴瘤之间缺失的环节，可归类为隐匿性肠病相关T细胞淋巴瘤。
