脊柱關節病外周關節滑膜高表達的RANK/RANKL/OPG系統與炎症呈部分分離

脊柱關節病外周關節滑膜高表達的RANK/RANKL/OPG系統與炎症呈部分分離
Vandooren B, et al. Arthritis Rheum. 2008;58:718-729

目的：脊 柱關節病(SpA)和類風溼關節炎(RA)的骨損傷模式不一樣，RA患者中骨侵蝕更顯著一些。RANK/RANKL/OPG系統經過促進破骨細胞和成熟與活 化從而在骨吸取中起到核心的做用。爲了評價該系統在獨特骨表型中的潛在做用，咱們研究了這些分子在SpA和RA外周關節炎性滑膜中的表達。

方法：從35例SpA和19例RA患者活動性炎性外周關節中活檢滑膜。從TNF拮抗劑治療後的24例SpA患者中得到相配對的滑膜標本。用免疫組化檢測滑膜組織中RANKL、OPG、RANK、TRAP表達，並用半定量評分和數字圖像分析進行評估。

結果：在 普遍驗證相應抗體的效力和特異性後，咱們證明SpA炎性滑膜中富表達RANKL和OPG。成纖維細胞樣滑膜細胞和襯裏下層T淋巴細胞均表達RANKL。炎 性組織中可見RANKL陽性破骨細胞前體細胞，但未見成熟的TRAP陽性破骨細胞。這些分子在非銀屑病SpA、銀屑病SpA以及RA患者中的表達並沒有差 異，它們的表達與系統性或局部炎症水平無關聯，並且高效的TNF拮抗劑治療並不能顯著改變這些分子的表達。只有在全身性抗TNF療效顯著的部分患者的滑膜 襯裏層中，RANKL呈表達下調。

結論：RANKL、OPG和RANK的定性或定量檢測結果不足以解釋TNF拮抗劑對於SpA患者骨侵蝕的相對骨保護做用。這些分子在SpA外周關節炎性滑膜中的高表達與全身性以及局部炎症呈顯著分離。

原文連接或參見如下信息。

Arthritis Rheum. 2008 Mar;58(3):718-29.
The abundant synovial expression of the RANK/RANKL/Osteoprotegerin system in peripheral spondylarthritis is partially disconnected from inflammation.
Vandooren B, Cantaert T, Noordenbos T, Tak PP, Baeten D.
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

Comment in: Arthritis Rheum. 2008 Mar;58(3):641-4.

OBJECTIVE: Spondylarthritis (SpA) and rheumatoid arthritis (RA) have different patterns of bone damage, with more pronounced bone erosions in RA. The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in bone resorption by promoting the maturation and activation of osteoclasts. To assess the potential role of this system in the distinct bone phenotype, we studied the synovial expression of these mediators in SpA and RA peripheral synovitis.

METHODS: Synovial biopsy specimens were obtained from the actively inflamed peripheral joints of 35 patients with SpA and 19 patients with RA. Paired synovial biopsy samples were obtained from 24 patients with SpA after tumor necrosis factor alpha (TNFalpha) blockade. Synovial tissue sections were immunostained for RANKL, OPG, RANK, and TRAP and assessed by semiquantitative scoring and digital image analysis.

RESULTS: After extensive validation of the reactivity and specificity of the antibodies, we demonstrated the abundant expression of RANKL and OPG in SpA synovitis. RANKL was expressed by both fibroblast-like synoviocytes and sublining T lymphocytes. RANK-positive osteoclast precursors but no mature TRAP-positive osteoclasts were present in the inflamed tissue. The expression of these mediators was not different between patients with nonpsoriatic SpA, patients with psoriatic SpA, and patients with RA, was not related to the degree of systemic or local inflammation, and was not significantly modulated by highly effective treatment with TNFalpha blockers. Only the subset of patients with the best systemic response to TNFalpha blockade had decreased RANKL expression in the intimal lining layer.

CONCLUSION: The relative protection against bone erosions in SpA cannot be explained by qualitative or quantitative differences in the synovial expression of RANKL, OPG, and RANK. The abundant expression of these factors in SpA peripheral synovitis is largely disconnected from systemic and local inflammation.

PMID: 18311801 [PubMed - indexed for MEDLINE]