Martini Giorgia, Biscaro Francesca, Boscaro Elisa, Calabrese Fiorella, Lunardi Francesca, Facco Monica, Agostini Carlo, Zulian Francesco, Fadini Gian Paolo
Paediatric Rheumatology Unit, Department of Paediatrics, 35128, Padova, Italy.
Department of Medicine, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy.
BMC Musculoskelet Disord. 2015 Apr 30;16:103. doi: 10.1186/s12891-015-0555-9.
Endothelial progenitor cells (EPC) promote angiogenesis and vascular repair. Though reduced EPC levels have been shown in rheumatoid arthritis, no study has so far evaluated EPCs in children with juvenile idiopathic arthritis (JIA). We aimed to study circulating EPCs in children with JIA, their relation to disease activity, and effects of anti TNF-α treatment.
Circulating EPCs were quantified by flow cytometry based on CD34, CD133 and KDR expression in peripheral blood of 22 patients with oligoarticular JIA and 29 age-matched controls. EPCs were re-assessed in children with methotrexate-resistant oligo-extended JIA before and up to 12 month after initiation of anti-TNF-alpha therapy. Plasma concentrations of inflammatory and EPC-regulating factors were measured using a multiplex array. Confocal immunofluorescence was used to demonstrate EPCs in synovial tissues.
Children with active JIA showed a significant reduction of relative and absolute counts of circulating progenitor cells and EPCs compared to age-matched healthy controls. CD34(+) cell levels were modestly and inversely correlated to disease activity. A strong inverse correlation was found between serum TNF-α and EPC levels. In 8 patients treated with anti TNF-α agents, the number of EPCs rose to values similar to healthy controls. CD34(+)KDR(+) EPCs were found in the synovial tissue of JIA children, but not in control.
Children with JIA have reduced levels of the vasculoprotective and proangiogenic EPCs. While EPCs may contribute to synovial tissue remodelling, EPC pauperization may indicate an excess cardiovascular risk if projected later in life.
内皮祖细胞（EPC）可促进血管生成和血管修复。尽管类风湿关节炎患者的EPC水平已被证实降低，但目前尚无研究评估幼年特发性关节炎（JIA）患儿的EPC情况。我们旨在研究JIA患儿循环EPC的情况、其与疾病活动度的关系以及抗TNF-α治疗的效果。
通过流式细胞术基于CD34、CD133和KDR的表达对22例少关节型JIA患儿及29例年龄匹配的对照者外周血中的循环EPC进行定量。对甲氨蝶呤抵抗的少关节扩展型JIA患儿在开始抗TNF-α治疗前及治疗后长达12个月时重新评估EPC。使用多重阵列测定炎症和EPC调节因子的血浆浓度。采用共聚焦免疫荧光法在滑膜组织中证实EPC。
与年龄匹配的健康对照相比，活动期JIA患儿的循环祖细胞和EPC的相对及绝对计数显著降低。CD34(+)细胞水平与疾病活动度呈适度负相关。血清TNF-α与EPC水平之间存在强烈的负相关。在8例接受抗TNF-α药物治疗的患者中，EPC数量升至与健康对照相似的值。在JIA患儿的滑膜组织中发现了CD34(+)KDR(+) EPC，但在对照中未发现。
JIA患儿具有血管保护和促血管生成的EPC水平降低的情况。虽然EPC可能有助于滑膜组织重塑，但如果在生命后期出现EPC减少，可能表明心血管风险增加。
