Serum antibodies to collagen XIII: a further good marker of active Graves' ophthalmopathy
Serum antibodies to collagen XIII: a further good marker of active Graves' ophthalmopathy
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DOI：
10.1111/j.1365-2265.2004.02167.x
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Bizzarro, A
中科院分区：
文献类型：
--
作者：
De Bellis, A;Sansone, D;Bizzarro, A
目的细胞间粘附分子-1（ICAM-1）在Graves'眼病（GO）患者眼眶淋巴细胞浸润中起重要作用，其可溶性血清水平与临床活动性评分（CAS）呈正相关。血清抗体对胶原蛋白XIII（CollXIIIAb），质膜蛋白在几乎所有的结缔组织生产细胞中以低水平表达，已被检测到在GO，但其意义尚不清楚。本研究的目的是在有和没有眼病的Graves病患者中寻找CollXIIAb，并将它们的水平与CAS和血清可溶性ICAM-1（sICAM-1）值相关联。28例中度和活动性眼病（第1组），其中12例甲状腺功能亢进（1a组）和16例甲状腺功能正常者甲状腺功能正常的轻度非活动性眼病13例（第2组）;无眼病25例（第3组），其中甲状腺功能亢进11例（第3a组），甲状腺功能正常14例（第3b组）。最后，用酶联免疫吸附试验（ELISA）检测26例正常人血清中CollXIIIAb的含量。在8/12例中检测到高水平的CollXIIIAb 1a组为66.6%（OD值0.529 ~ 0.894），1b组为10/16（62.5%）（OD值0.560-0.855）。在第2组患者中，检测到CollXIIAb，但在4/13例（30.7%）患者中处于低水平（OD 0.205-0.260）。在第3组患者中，CollXIIIAb在第3a组的6/11（54.5%）和第3b组的5/14（35.7%）中以低水平存在（OD分别为0.215-0.290和0.144-0.245）。CollXIIIAb仅在4/26例正常对照中检出（15%），但水平较低（OD 0.150-0.185）。组1a和1b中的CollXIIIAb值均显著高于其余组。在1a、1b和2组中，CollXIIIAb水平与CAS呈正相关，但与甲状腺激素水平无关。此外，CollXIIIAb水平和sICAM-1值之间的正相关性也证明了在所有三个groups.Conclusions我们的研究结果表明，CollXIIIAb可以被认为是一个更好的标记活跃的炎症过程，涉及脂肪结缔组织在GO。特别是，活动性眼病的Graves患者血清中高水平的CollXIIIAb可能反映了这些患者中活化的成纤维细胞膜上XIII型胶原的表达增加。因此，这些抗体的评价可以添加到其他已知的标记物中，作为监测Graves患者和调节GO治疗的有用且廉价的工具。
Objective In Graves' ophthalmopathy (GO) intercellular adhesion molecule-1 (ICAM-1) is thought to play a key role in lymphocyte infiltration into the orbit, and serum levels of its soluble form are positively correlated to clinical activity score (CAS). Serum antibodies against collagen XIII (CollXIIIAb), a plasma membrane protein expressed at a low level in almost all connective tissue-producing cells, have been detected in GO, but their significance is unclear. The aim of this study was to search for CollXIIIAb in Graves' patients with and without ophthalmopathy and to correlate their levels with CAS and with serum soluble ICAM-1 (sICAM-1) values.Patients We studied 66 patients with Graves' disease whose sera had been previously tested for sICAM-1 levels, grouped as follows: 28 with moderate and active ophthalmopathy (group 1), 12 of them hyperthyroid (group 1a) and 16 euthyroid (group 1b); 13 with mild and inactive ophthalmopathy and normal thyroid function (group 2); 25 without ophthalmopathy (group 3), 11 of them hyperthyroid (group 3a) and 14 euthyroid (group 3b). Finally, 26 sera of normal controls were studied.Measurements CollXIIIAb were evaluated by an enzyme-linked immunosorbent assay (ELISA) method.Results In group 1 patients, CollXIIIAb were detected at high levels in 8/12 (66.6%) in group 1a [optical density (OD) ranging from 0.529 to 0.894] and in 10/16 (62.5%) in group 1b (OD 0.560-0.855). In group 2 patients, CollXIIIAb were detected but at low levels (OD 0.205-0.260) in 4/13 patients (30.7%). In group 3 patients, CollXIIIAb were present at low levels in 6/11 (54.5%) of group 3a and in 5/14 (35.7%) of group 3b (OD 0.215-0.290 and 0.144-0.245, respectively). CollXIIIAb were detected in only 4/26 normal controls (15%) but at low levels (OD 0.150-0.185). CollXIIIAb values in both groups 1a and 1b were significantly higher than those of the remaining groups. A positive correlation between CollXIIIAb levels and CAS but not thyroid hormone levels was found in groups 1a, 1b and 2. Moreover, a positive correlation between CollXIIIAb levels and sICAM-1-values was also evidenced in all three groups.Conclusions Our results suggest that CollXIIIAb could be considered as a further good marker of active inflammatory processes involving the adipose connective tissue in GO. In particular, the high levels of CollXIIIAb in sera of Graves' patients with active ophthalmopathy could reflect an increased expression of type XIII collagen on the membrane of activated fibroblasts in these patients. Thus, the evaluation of these antibodies could be added to other known markers as a useful and inexpensive tool in monitoring Graves' patients and in modulating the treatment of GO.