Firestein G S, Paine M M, Littman B H
Division of Rheumatology, University of California, San Diego 92103.
Arthritis Rheum. 1991 Sep;34(9):1094-105. doi: 10.1002/art.1780340905.
In situ hybridization was used to localize and quantify gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Collagenase, tissue inhibitor of metalloproteinases (TIMP), HLA-DR, and complement (C2 and C3) gene expression was studied in synovial tissue from 23 patients with RA, OA, or other inflammatory arthropathies. Gene expression was highly compartmentalized: Collagenase, TIMP, and C2 messenger RNA (mRNA) were localized primarily to the synovial lining layer; HLA-DR mRNA was prominent in the lining and in some sublining lymphoid aggregates; the C3 probe hybridized only to sublining lymphoid aggregates. Relative mRNA levels were quantified using computer-assisted image analysis. There was significantly more collagenase, C2, C3, and HLA-DR mRNA in RA compared with OA patients. However, TIMP mRNA levels were similar in RA and OA. Expression of collagenase, TIMP, C2, C3, and HLA-DR genes correlated with the degree of synovial inflammation. The effect of intraarticular corticosteroid injection on synovial tissue gene expression was studied using serial percutaneous synovial biopsy samples from the knees of 3 RA patients. Joints were biopsied, injected with triamcinolone, and rebiopsied 1-2 weeks later. Histologic inflammation scores were lower in posttreatment synovia. Collagenase and TIMP mRNA, although abundant in presteroid samples, were nearly undetectable in post-steroid tissues. HLA-DR mRNA levels also were significantly decreased. C2 and C3 hybridization significantly decreased in 2 of 3 patients and 1 of 3 patients, respectively. Hence, clinical response to intraarticular steroid therapy was accompanied by histologic improvement and decreased expression of genes that play a role in articular destruction.(ABSTRACT TRUNCATED AT 250 WORDS)
原位杂交用于定位和定量类风湿关节炎（RA）和骨关节炎（OA）滑膜组织中的基因表达。研究了23例患有RA、OA或其他炎性关节病患者滑膜组织中胶原酶、金属蛋白酶组织抑制剂（TIMP）、HLA-DR和补体（C2和C3）的基因表达。基因表达高度分区化：胶原酶、TIMP和C2信使核糖核酸（mRNA）主要定位于滑膜衬里层；HLA-DR mRNA在衬里层和一些衬里下淋巴聚集物中显著；C3探针仅与衬里下淋巴聚集物杂交。使用计算机辅助图像分析对相对mRNA水平进行定量。与OA患者相比，RA患者中胶原酶、C2、C3和HLA-DR mRNA明显更多。然而，RA和OA中TIMP mRNA水平相似。胶原酶、TIMP、C2、C3和HLA-DR基因的表达与滑膜炎症程度相关。使用来自3例RA患者膝关节的系列经皮滑膜活检样本研究关节内注射皮质类固醇对滑膜组织基因表达的影响。对关节进行活检，注射曲安奈德，1 - 2周后再次活检。治疗后滑膜的组织学炎症评分较低。胶原酶和TIMP mRNA虽然在类固醇治疗前的样本中丰富，但在类固醇治疗后的组织中几乎检测不到。HLA-DR mRNA水平也显著降低。C2和C3杂交在3例患者中的2例和3例患者中的1例中分别显著降低。因此，关节内类固醇治疗的临床反应伴随着组织学改善以及在关节破坏中起作用的基因表达降低。（摘要截取自250字）
