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Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy
Arthritis Research & Therapy ( IF 4.4 ) Pub Date : 2024-09-11 , DOI: 10.1186/s13075-024-03387-6 Hongxia Yang 1, 2 , Chao Sun 1 , Lifang Ye 1 , Yuetong Xu 1 , Sang Lin 1 , Qinglin Peng 1 , Guochun Wang 1 , Xin Lu 1
Arthritis Research & Therapy ( IF 4.4 ) Pub Date : 2024-09-11 , DOI: 10.1186/s13075-024-03387-6 Hongxia Yang 1, 2 , Chao Sun 1 , Lifang Ye 1 , Yuetong Xu 1 , Sang Lin 1 , Qinglin Peng 1 , Guochun Wang 1 , Xin Lu 1
Affiliation
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician’s Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (β = 3.830; p < 0.0001), muscle VAS (β = 2.893; p < 0.0001), MMT8 (β=-19.368; p < 0.0001), and creatine kinase (CK) levels (β = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (β = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis. • Anti-HMGCR IgM-positive patients had a younger age of onset and more neck weakness than anti-HMGCR IgM-negative patients. • The levels of anti-HMGCR IgG and IgM are associated with disease activity in anti-HMGCR-positive patients. • Anti-HMGCR IgM is associated with refractory outcome and poor prognosis.
中文翻译:
IgM 同种型抗 HMGCR 抗体与难治性免疫介导的坏死性肌病的关联
抗 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 自身抗体是肌炎特异性抗体之一,与免疫介导的坏死性肌病 (IMNM) 相关。然而,抗 HMGCR 同种型与预后之间的关系尚未得到充分研究。本研究的目的是深入了解抗 HMGCR 抗体阳性的 IMNM 患者的抗 HMGCR 同种型与临床和预后之间的关联。通过酶联免疫吸附测定 (ELISA) 评估从 71 名基线时抗 HMGCR IgG 呈阳性的患者获得的 123 个连续血清样本中的抗 HMGCR 同种型(IgG、IgA 和 IgM)水平。通过手动肌肉测试 (MMT) 8、医师整体评估 (PGA) 视觉模拟量表 (VAS) 和肌肉 VAS 来评估疾病活动性。基线抗 HMGCR IgG 水平与 PGA VAS (r = 0.24; p = 0.04)、肌肉 VAS (r = 0.32; p < 0.01) 和 MMT8(r=-0.24; p = 0.04) 以及基线抗 HMGCR IgG 水平相关。 -HMGCR IgM 水平与 PGA VAS (r = 0.27, p = 0.02)、肌肉 VAS (r = 0.24, p = 0.04) 呈正相关。抗 HMGCR IgM 阳性患者的发病年龄较低 [29(25,46) vs. 51(33,65),p = 0.006],颈部无力的比例较高(63.5% vs. 34.6%,p = 0.031) 与抗 HMGCR IgM 阴性患者相比。纵向分析表明,抗 HMGCR IgG 水平的变化与 PGA VAS (β = 3.830; p < 0.0001)、肌肉 VAS (β = 2.893; p < 0.0001)、MMT8 (β=- 19.368;p < 0.0001) 和肌酸激酶 (CK) 水平(β = 3900.05,p < 0.0001)。基线时抗 HMGCR IgM 水平与抗 HMGCR IgA 水平呈弱相关(r = 0.33,p < 0.01),抗 HMGCR IgA 水平的变化与随访期间抗 HMGCR IgM 水平的变化相关(β = 0.885;p < 0.0001)。抗 HMGCR IgM 患者表现出难治性病程的患者多于抗 HMGCR IgM 阴性患者(多周期病程:40% vs. 25%;慢性持续病程:46.7% vs. 20.5%,p = 0.018) 。在抗HMGCR IgG阳性IMNM患者中,抗HMGCR IgG水平与疾病活动性相关,抗HMGCR IgM与难治性结果和不良预后相关。 • 与抗HMGCR IgM 阴性患者相比,抗HMGCR IgM 阳性患者发病年龄更小,颈部无力更严重。 • 抗HMGCR IgG 和IgM 水平与抗HMGCR 阳性患者的疾病活动性相关。 • 抗HMGCR IgM 与难治性结果和不良预后相关。
更新日期:2024-09-11
中文翻译:
IgM 同种型抗 HMGCR 抗体与难治性免疫介导的坏死性肌病的关联
抗 3-羟基-3-甲基戊二酰辅酶 A 还原酶 (HMGCR) 自身抗体是肌炎特异性抗体之一,与免疫介导的坏死性肌病 (IMNM) 相关。然而,抗 HMGCR 同种型与预后之间的关系尚未得到充分研究。本研究的目的是深入了解抗 HMGCR 抗体阳性的 IMNM 患者的抗 HMGCR 同种型与临床和预后之间的关联。通过酶联免疫吸附测定 (ELISA) 评估从 71 名基线时抗 HMGCR IgG 呈阳性的患者获得的 123 个连续血清样本中的抗 HMGCR 同种型(IgG、IgA 和 IgM)水平。通过手动肌肉测试 (MMT) 8、医师整体评估 (PGA) 视觉模拟量表 (VAS) 和肌肉 VAS 来评估疾病活动性。基线抗 HMGCR IgG 水平与 PGA VAS (r = 0.24; p = 0.04)、肌肉 VAS (r = 0.32; p < 0.01) 和 MMT8(r=-0.24; p = 0.04) 以及基线抗 HMGCR IgG 水平相关。 -HMGCR IgM 水平与 PGA VAS (r = 0.27, p = 0.02)、肌肉 VAS (r = 0.24, p = 0.04) 呈正相关。抗 HMGCR IgM 阳性患者的发病年龄较低 [29(25,46) vs. 51(33,65),p = 0.006],颈部无力的比例较高(63.5% vs. 34.6%,p = 0.031) 与抗 HMGCR IgM 阴性患者相比。纵向分析表明,抗 HMGCR IgG 水平的变化与 PGA VAS (β = 3.830; p < 0.0001)、肌肉 VAS (β = 2.893; p < 0.0001)、MMT8 (β=- 19.368;p < 0.0001) 和肌酸激酶 (CK) 水平(β = 3900.05,p < 0.0001)。基线时抗 HMGCR IgM 水平与抗 HMGCR IgA 水平呈弱相关(r = 0.33,p < 0.01),抗 HMGCR IgA 水平的变化与随访期间抗 HMGCR IgM 水平的变化相关(β = 0.885;p < 0.0001)。抗 HMGCR IgM 患者表现出难治性病程的患者多于抗 HMGCR IgM 阴性患者(多周期病程:40% vs. 25%;慢性持续病程:46.7% vs. 20.5%,p = 0.018) 。在抗HMGCR IgG阳性IMNM患者中,抗HMGCR IgG水平与疾病活动性相关,抗HMGCR IgM与难治性结果和不良预后相关。 • 与抗HMGCR IgM 阴性患者相比,抗HMGCR IgM 阳性患者发病年龄更小,颈部无力更严重。 • 抗HMGCR IgG 和IgM 水平与抗HMGCR 阳性患者的疾病活动性相关。 • 抗HMGCR IgM 与难治性结果和不良预后相关。