Presence and Implications of Anti-Angiotensin Converting Enzyme-2 Immunoglobulin M Antibodies in Anti-Melanoma-Differentiation-Associated 5 Dermatomyositis.
Presence and Implications of Anti-Angiotensin Converting Enzyme-2 Immunoglobulin M Antibodies in Anti-Melanoma-Differentiation-Associated 5 Dermatomyositis.
复制标题
抗血管紧张素转化酶-2免疫球蛋白M抗体在抗黑质化差异相关的5个皮肌炎中的存在和含义。
DOI：
10.1002/acr2.11423
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发表时间：
2022-05
影响因子：
3.4
通讯作者：
Casciola-Rosen, Livia
中科院分区：
文献类型：
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作者：
Mecoli, Christopher A;Yoshida, Akira;Paik, Julie J;Lin, Cheng Ting;Danoff, Sonye;Hanaoka, Hironari;Rosen, Antony;Christopher-Stine, Lisa;Kuwana, Masataka;Casciola-Rosen, Livia
抗黑色素瘤分化相关 5 (抗 MDA5) 阳性皮肌炎 (DM) 患者与 SARS-CoV-2 患者有一些惊人的相似之处。我们的目的是评估在两个独立的抗 MDA5 阳性 DM 队列中重症 SARS-CoV-2 患者中发现的抗血管紧张素转换酶 2 (ACE2) 免疫球蛋白 M (IgM) 抗体的患病率。通过酶联免疫吸附测定 (ELISA) 在两个抗 MDA5 阳性 DM 队列中检测抗 ACE2 IgM 抗体：主要是门诊北美队列 (n = 52) 和富含新发疾病的日本队列 (n = 32)。此外，还通过 ELISA 检测了 118 名临床严重程度不同的 SARS-CoV-2 患者的抗 MDA5 抗体。 52 名北美患者中的 5 名 (9.6%) 和 32 名日本患者中的 5 名 (15%) 抗 ACE2 IgM 呈阳性。在北美队列中，与抗 ACE2-IgM 阴性患者相比，所有 5 名具有抗 ACE2 IgM 抗体的患者均出现近端肌无力，患有间质性肺病，接受脉冲剂量甲基强的松龙的可能性显着更高（80% vs 30%，P = 0.043），并且用力肺活量较差（中位预测值 59% vs 78%，P = 0.056）组。在日本队列中，所有 5 名抗 ACE2-IgM 阳性患者也需要脉冲剂量甲基泼尼松龙，五名患者中的三名 (60%) 死亡。与 IgM 阴性患者相比，抗 ACE2 IgM 的日本患者氧合明显较差，即氧分压 (PaO2)/吸入氧分数 (FiO2) 比值较低（233 vs 390，P = 0.021），以及较高的肺泡动脉氧合梯度（91 vs 23mm Hg，P = 0.024）组。我们描述了两个独立的抗 MDA5 阳性 DM 队列中的抗 ACE2 IgM 自身抗体。这些自身抗体可能是严重疾病的生物标志物，并提供对疾病发病机制的深入了解。
Patients with anti‐melanoma‐differentiation‐associated 5 (anti‐MDA5)‐positive dermatomyositis (DM) share several striking similarities to patients with SARS‐CoV‐2. Our objective was to assess the prevalence of anti‐angiotensin converting enzyme‐2 (ACE2) immunoglobulin M (IgM) antibodies, found in patients with severe SARS‐CoV‐2, in two independent anti‐MDA5‐positive DM cohorts. Anti‐ACE2 IgM antibodies were assayed by enzyme‐linked immunosorbent assay (ELISA) in two anti‐MDA5‐positive DM cohorts: a predominantly outpatient North American cohort (n = 52) and a Japanese cohort enriched for new‐onset disease (n = 32). Additionally, 118 patients with SARS‐CoV‐2 with a spectrum of clinical severity were tested for anti‐MDA5 antibodies by ELISA. Five of fifty‐two (9.6%) North American patients and five of thirty‐two (15%) Japanese patients were positive for anti‐ACE2 IgM. In the North American cohort, all five patients with anti‐ACE2 IgM antibodies had proximal muscle weakness, had interstitial lung disease, were significantly more likely to receive pulse dose methylprednisolone (80% vs 30%, P = 0.043), and had worse forced vital capacity (median 59% predicted vs 78%, P = 0.056) compared with the anti‐ACE2‐IgM‐negative group. In the Japanese cohort, all five anti‐ACE2‐IgM‐positive patients also required pulse dose methylprednisolone, and three of five (60%) patients died. Japanese patients with anti‐ACE2 IgM had significantly worse oxygenation, as defined by a lower partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (233 vs 390, P = 0.021), and a higher alveolar‐arterial oxygenation gradient (91 vs 23 mm Hg, P = 0.024) than the IgM‐negative group. We describe anti‐ACE2 IgM autoantibodies in two independent cohorts with anti‐MDA5‐positive DM. These autoantibodies may be biomarkers for severe disease and provide insight into disease pathogenesis.