Novel serum autoantibodies against ß-actin (ACTB) in amyotrophic lateral sclerosis.
Novel serum autoantibodies against ß-actin (ACTB) in amyotrophic lateral sclerosis.
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新型血清自身抗体
DOI：
10.1080/21678421.2021.1885448
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Kuwabara S.
中科院分区：
文献类型：
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作者：
Sugimoto K;Mori M;Liu J;Shibuya K;Isose S;Koide M;Hiwasa T;Kuwabara S.
采用血清学分析重组cDNA表达文库（SEREX）方法筛选肌萎缩侧索硬化（ALS）新的生物标志物，并评价其临床意义。使用SEREX方法筛选ALS患者血清中的自身抗体。鉴定的自身抗体通过使用扩增发光邻近均相测定联免疫吸附测定（AlphaLISA）测量70名ALS患者、60名正常对照（NC）和62名帕金森病（PD）患者的血清水平来验证。在ALS患者中研究这些自身抗体的临床相关性。SEREX鉴定了16种候选抗原，包括β-肌动蛋白（ACTB）以及我们先前报道的蛋白酶体α亚基7（PSMA 7），ALS患者血清中抗ACTB抗体水平显著高于NC（p< 0.001）和PD患者（p= 0.001）。此外，委员会认为，晚期ALS患者血清抗ACTB抗体水平较高，（King's ALS临床分期的第4阶段）和残疾更严重的患者（ALS功能评定量表修订版[ALSFRS-R]评分< 40.5）与早期相比（2期[累及第2个区域]）患者和残疾程度较轻的患者（ALSFRS-R评分≥ 40.5）（p= 0.003，p = 0.014）。抗ACTB抗体水平与ALSFRS-R评分呈负相关（ρ = − 0.409，p = 0.001），与临床疾病分期呈正相关（ρ = 0.355，p = 0.003），与病程呈弱正相关（ρ = 0.294，p = 0.014）。抗ACTB抗体可能是ALS的潜在生物标志物，可以指示疾病的严重程度。
To identify novel biomarkers using the serological analysis of recombinant cDNA expression libraries (SEREX) method and to evaluate their clinical significance in amyotrophic lateral sclerosis (ALS). Serum of ALS patients were screened for autoantibodies using the SEREX method. The identified autoantibodies were validated by measuring their serum levels in 70 ALS patients, 60 normal controls (NC), and 62 Parkinson disease (PD) patients using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA). The clinical relevance of these autoantibodies was investigated in ALS patients. SEREX identified 16 candidate antigens including β-actin (ACTB) in addition to proteasome subunit alpha type 7 (PSMA7) that we previously reported, and serum levels of antibodies against ACTB, were significantly higher in ALS patients than in NC (p< 0.001) and PD patients (p= 0.001). Moreover, serum levels of anti-ACTB antibody were higher in advanced stage ALS patients (Stage 4 on the King’s ALS clinical staging) and in those with more severe disability (ALS Functional Rating Scale revised [ALSFRS-R] score < 40.5) compared to early stage (Stage 2 [2nd region involved)]) patients and those with less severe disability (ALSFRS-R score ≥ 40.5) (p= 0.003,p= 0.014). Anti-ACTB antibody levels were also negatively correlated with ALSFRS-R score (ρ = −0.409,p= 0.001), but positively correlated with clinical disease stage (ρ = 0.355,p= 0.003), and showed a weak positive correlation with disease duration (ρ = 0.294,p= 0.014). Anti-ACTB antibodies may be a potential biomarker of ALS could indicate disease severity.