Reumatologia, Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, viale del Policlinico 155, I-00161 Rome, Italy.
Arthritis Res Ther. 2011 Jul 8;13(4):R111. doi: 10.1186/ar3396.
Single nucleotide polymorphisms (SNPs) of transforming growth factor β (TGF-β) and IL-6 genes (respectively, 869C/T and -174G/C) have been associated with radiographic severity of bone-erosive damage in patients with rheumatoid arthritis (RA). Musculoskeletal ultrasound (US) is more sensitive than radiography in detecting bone erosion. We analyzed the association between TGF-β 869C/T and IL-6 -174G/C SNPs and bone-erosive damage, evaluated by US, in a cohort of patients with severely active RA.
Seventy-seven patients were enrolled before beginning anti-TNF treatment. Disease activity was measured using the disease activity score in 28 joints, and the clinical response was evaluated according to the European League Against Rheumatism response criteria. Rheumatoid factor (RF) and anticitrullinated protein/peptide antibodies (ACPAs) were detected. The 869C/T TGF-β and -174G/C IL-6 SNPs were analyzed by PCR amplification. US was performed to assess the bone surfaces of metacarpophalengeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints by obtaining multiplanar scans. According to the number of erosions per joint, a semiquantitative score ranging from 0 to 3 was calculated in each anatomical site to obtain a MCP total erosion score (TES), a PIP TES and a MTP TES, all ranging from 0 to 30, and a global patient TES calculated as the sum of these scores (range, 0 to 90).
Patients carrying the TGF-β 869TT genotype showed a statistically significant lower MTP TES than those with the CC or CT genotype (mean MTP TES ± standard deviation for 869TT 6.3 ± 5.7 vs. 869CC/CT 11.7 ± 7.8; P = 0.011). Interestingly, patients with the TT genotype showed dichotomous behavior that was dependent on autoantibody status. In the presence of ACPAs and/or RF, the TT genotype was associated with lower erosion scores at all anatomical sites compared with the CC and CT genotypes. Conversely, the same 869TT patients showed higher erosion scores in the absence of ACPAs or RF.
In RA patients, TGF-β 869C/T SNPs could influence the bone-erosive damage as evaluated by US. The serological autoantibody status (ACPAs and RF) can modulate this interaction.
转化生长因子β（TGF-β）和白细胞介素 6（IL-6）基因的单核苷酸多态性（SNPs）分别与类风湿关节炎（RA）患者的骨侵蚀性损害的放射学严重程度相关。肌肉骨骼超声（US）比放射照相术更能敏感地检测到骨侵蚀。我们分析了 TGF-β 869C/T 和 IL-6-174G/C SNP 与 US 评估的严重活跃性 RA 患者的骨侵蚀损害之间的关联。
在开始抗 TNF 治疗之前，纳入了 77 名患者。使用 28 关节疾病活动评分测量疾病活动度，并根据欧洲抗风湿联盟反应标准评估临床反应。检测类风湿因子（RF）和抗瓜氨酸蛋白/肽抗体（ACPA）。通过 PCR 扩增分析 869C/T TGF-β 和-174G/C IL-6 SNP。通过获得多平面扫描来评估掌指（MCP）、近端指间（PIP）和跖趾（MTP）关节的骨表面。根据每个关节的侵蚀数，在每个解剖部位计算 0 至 3 的半定量评分，以获得 MCP 总侵蚀评分（TES）、PIP TES 和 MTP TES，范围均为 0 至 30，以及作为这些评分总和的总体患者 TES（范围为 0 至 90）。
携带 TGF-β 869TT 基因型的患者的 MTP TES 明显低于 CC 或 CT 基因型的患者（869TT 的平均 MTP TES ±标准偏差为 6.3 ± 5.7，869CC/CT 为 11.7 ± 7.8；P = 0.011）。有趣的是，TT 基因型的患者表现出依赖于自身抗体状态的二分法行为。在存在 ACPA 和/或 RF 的情况下，与 CC 和 CT 基因型相比，TT 基因型与所有解剖部位的侵蚀评分较低相关。相反，在不存在 ACPA 或 RF 的情况下，相同的 869TT 患者表现出更高的侵蚀评分。
在 RA 患者中，TGF-β 869C/T SNP 可能会影响 US 评估的骨侵蚀损害。血清自身抗体状态（ACPA 和 RF）可以调节这种相互作用。
