结节病中的功能基因组学与预后——抗原呈递的关键作用

Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.

作者信息

Rutherford Robert M, Staedtler Frank, Kehren Jeanne, Chibout Salah-Dine, Joos Ladina, Tamm Michel, Gilmartin John J, Brutsche Martin H

机构信息

Department of Respiratory Medicine, University Hospital, Galway, Ireland.

出版信息

Sarcoidosis Vasc Diffuse Lung Dis. 2004 Mar;21(1):10-8.

PMID:15127969

Abstract

BACKGROUND

Sarcoidosis is a systemic disorder of unknown cause, highly variable phenotype and unpredictable outcome. Antigen processing, inflammatory response and immunomodulation appear critical to development and prognosis of the disease.

METHODS

We performed a comprehensive genomic analysis, applying high-density human GeneChip probe arrays (HUG95A, Affymetrix Inc.) for gene expression profiling from peripheral blood of patients with acute pulmonary sarcoidosis (n = 12) and matched healthy controls (n = 12), mean age 36 +/- 12 and 33 +/- 10 years respectively.

RESULTS

At follow-up (18 [15-24] months), 7 patients had self-limited disease and 5 had persistent disease. Significantly different expression comparing patients and controls was identified for 1,860 (14.9%) and 729 (5.8%) gene products at p = 0.05 and p = 0.01 levels respectively. Genes closely associated with persistent disease included HLA-DRB11501 DQB10602, TNFA, NFKB, cyclic AMP-responsive element modulator (CREM) and T-cell activation marker CD69. IL1B, IL8, growth related (GRO)-beta/-gamma and CCR 2,5,6 were closely associated with self-limited disease.

CONCLUSION

We hypothesize that, in self-limited disease, greater effector cell activation leads to successful antigen elimination/tolerance, whereas HLA-DRB11501 DQBI0602-mediated, probably defective/partial T-lymphocyte activation results in an inefficient primary immune response, antigen intolerance and persistent disease.

摘要

背景

结节病是一种病因不明、表型高度可变且预后不可预测的全身性疾病。抗原加工、炎症反应和免疫调节似乎对该疾病的发生发展及预后至关重要。

方法

我们进行了一项全面的基因组分析，应用高密度人类基因芯片探针阵列（HUG95A，Affymetrix公司）对急性肺结节病患者（n = 12）和匹配的健康对照者（n = 12）的外周血进行基因表达谱分析，患者和对照者的平均年龄分别为36±12岁和33±10岁。

结果

在随访（18 [15 - 24]个月）时，7例患者病情自限，5例患者病情持续。在p = 0.05和p = 0.01水平时，分别鉴定出1860种（14.9%）和729种（5.8%）基因产物在患者和对照者之间存在显著差异表达。与病情持续密切相关的基因包括HLA - DRB11501 DQB10602、TNFA、NFKB、环磷酸腺苷反应元件调节剂（CREM）和T细胞活化标志物CD69。IL1B、IL8、生长相关（GRO）-β/-γ和CCR 2、5、6与病情自限密切相关。