脊柱关节病外周关节滑膜高表达的RANK/RANKL/OPG系统与炎症呈部分分离

脊柱关节病外周关节滑膜高表达的RANK/RANKL/OPG系统与炎症呈部分分离
Vandooren B, et al. Arthritis Rheum. 2008;58:718-729

目的：脊
柱关节病(SpA)和类风湿关节炎(RA)的骨损伤模式不同，RA患者中骨侵蚀更显著一些。RANK/RANKL/OPG系统通过促进破骨细胞和成熟与活
化从而在骨吸收中起到核心的作用。为了评价该系统在独特骨表型中的潜在作用，我们研究了这些分子在SpA和RA外周关节炎性滑膜中的表达。

方法：从35例SpA和19例RA患者活动性炎性外周关节中活检滑膜。从TNF拮抗剂治疗后的24例SpA患者中获得相配对的滑膜标本。用免疫组化检测滑膜组织中RANKL、OPG、RANK、TRAP表达，并用半定量评分和数字图像分析进行评估。

结果：在
广泛验证相应抗体的效力和特异性后，我们证实SpA炎性滑膜中富表达RANKL和OPG。成纤维细胞样滑膜细胞和衬里下层T淋巴细胞均表达RANKL。炎
性组织中可见RANKL阳性破骨细胞前体细胞，但未见成熟的TRAP阳性破骨细胞。这些分子在非银屑病SpA、银屑病SpA以及RA患者中的表达并无差
异，它们的表达与系统性或局部炎症水平无关联，而且高效的TNF拮抗剂治疗并不能显著改变这些分子的表达。只有在全身性抗TNF疗效显著的部分患者的滑膜
衬里层中，RANKL呈表达下调。

结论：RANKL、OPG和RANK的定性或定量检测结果不足以解释TNF拮抗剂对于SpA患者骨侵蚀的相对骨保护作用。这些分子在SpA外周关节炎性滑膜中的高表达与全身性以及局部炎症呈显著分离。

原文链接或参见以下信息。

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]