Barbasso Helmers Sevim, Englund Pernilla, Engström Marianne, Ahlin Erik, Fathi Maryam, Janciauskiene Sabina, Heimbürger Mikael, Rönnelid Johan, Lundberg Ingrid E
Karolinska University Hospital Solna, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden.
Arthritis Rheum. 2009 Aug;60(8):2524-30. doi: 10.1002/art.24683.
To investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs).
Patients' sera were selected based on the presence or absence of anti-Jo-1, anti-SSA, or anti-U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC-L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM-1) expression was conducted by immunofluorescence (n=22) and by cell-based enzyme-linked immunosorbent assay (ELISA) (n=20). Serum levels of soluble ICAM-1 (sICAM-1) were determined by ELISA.
Sera from PM patients with ILD who were positive for anti-Jo-1 autoantibodies had a significantly stronger effect on the expression of ICAM-1 by HMVEC-L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM-1 expression. Higher serum levels of sICAM-1 were found in patients with myositis compared with healthy controls.
EC activation with ICAM-1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti-Jo-1 autoantibodies. The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies.
研究多发性肌炎(PM)和皮肌炎(DM)患者(伴或不伴间质性肺疾病(ILD))的血清或纯化IgG是否能激活内皮细胞(ECs)。
根据是否存在抗Jo-1、抗SSA或抗U1小核糖核蛋白自身抗体选择患者血清。通过线性印迹法测定自身抗体的存在情况。将来自肺组织的培养人微血管内皮细胞(HMVEC-L)与22例PM患者、7例DM患者的血清或纯化IgG以及10名健康个体作为对照进行孵育。通过免疫荧光法(n = 22)和基于细胞的酶联免疫吸附测定(ELISA)(n = 20)评估细胞间黏附分子1(ICAM-1)的表达。通过ELISA测定可溶性ICAM-1(sICAM-1)的血清水平。
与健康对照和其他自身抗体患者的血清相比,抗Jo-1自身抗体阳性的伴ILD的PM患者血清对HMVEC-L中ICAM-1表达的影响明显更强。纯化的IgG未诱导ICAM-1表达。与健康对照相比,肌炎患者血清中sICAM-1水平更高。
ICAM-1表达介导的EC激活可能导致携带抗Jo-1自身抗体的患者出现多器官受累,包括肌炎和ILD的发生。EC激活因子不是自身抗体本身,而是可能与这些自身抗体相关的全身因素。