Galindo-Feria Angeles S, Lodin Karin, Horuluoglu Begum, Sarrafzadeh-Zargar Sepehr, Wigren Edvard, Gräslund Susanne, Danielsson Olof, Wahren-Herlenius Marie, Dastmalchi Maryam, Lundberg Ingrid E
Department of Medicine, Division of Rheumatology, Karolinska Institutet, Stockholm, Sweden.
Center for Molecular Medicine, Division for Rheumatology, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Rheumatology (Oxford). 2025 Mar 1;64(3):1482-1492. doi: 10.1093/rheumatology/keae317.
To determine prevalence and clinical associations of anti-Four-and-a-half-LIM-domain 1 (FHL1) autoantibodies in patients with idiopathic inflammatory myopathies (IIM) and to evaluate autoantibody levels over time.
Sera at the time of diagnosis from patients with IIM (n = 449), autoimmune disease controls (DC, n = 130), neuromuscular diseases (NMDs, n = 16) and healthy controls (HC, n = 100) were analysed for anti-FHL1 autoantibodies by enzyme-linked immunosorbent assay (ELISA). Patients with IIM FHL1+ and FHL1- were included in a longitudinal analysis. Serum levels were correlated to disease activity.
Autoantibodies to FHL1 were more frequent in patients with IIM (122/449, 27%) compared with DC (autoimmune DC and NMD, 13/146, 9%, P < 0.001) and HC (3/100.3%, P < 0.001). Anti-FHL1 levels were higher in IIM [median (IQR)=0.62 (0.15-1.04)] in comparison with DC [0.22 (0.08-0.58)], HC [0.35 (0.23-0.47)] and NMD [0.48 (0.36-0.80)] P < 0.001. Anti-FHL1+ patients with IIM were younger at the time of diagnosis compared with the anti-FHL1- group (P = 0.05) and were seronegative for other autoantibodies in 25%.In the first follow-up, anti-FHL1+ sample 20/33 (60%) positive at baseline had turned negative for anti-FHL1 autoantibodies. Anti-FHL1 autoantibodies rarely appeared after initiating treatment. Anti-FHL1 autoantibody levels correlated with CK (r = 0.62, P= 0.01), disease activity measured using the Myositis Disease Activity Assessment Tool (MYOACT) (n = 14, P = 0.004) and inversely with Manual Muscle Test-8 (r = -0.59, P = 0.02) at baseline.
Anti-FHL1 autoantibodies were present in 27% of patients with IIM; of these, 25% were negative for other autoantibodies. Other autoimmune diseases had lower frequencies and levels. Anti-FHL1 levels often decreased with immunosuppressive treatment, correlated with disease activity measures at diagnosis and rarely appeared after start of treatment.
确定抗四半LIM结构域1（FHL1）自身抗体在特发性炎性肌病（IIM）患者中的患病率及临床关联，并评估自身抗体水平随时间的变化。
采用酶联免疫吸附测定（ELISA）分析IIM患者（n = 449）、自身免疫性疾病对照（DC，n = 130）、神经肌肉疾病（NMD，n = 16）和健康对照（HC，n = 100）诊断时的血清抗FHL1自身抗体。IIM FHL1阳性和FHL1阴性患者纳入纵向分析。血清水平与疾病活动度相关。
与DC（自身免疫性DC和NMD，13/146，9%，P < 0.001）和HC（3/100，3%，P < 0.001）相比，IIM患者中抗FHL1自身抗体更常见（122/449，27%）。与DC [0.22（0.08 - 0.58）]、HC [0.35（0.23 - 0.47）]和NMD [0.48（0.36 - 0.80）]相比，IIM患者抗FHL1水平更高[中位数（IQR）= 0.62（0.15 - 1.04）]，P < 0.001。与抗FHL1阴性组相比，IIM抗FHL1阳性患者诊断时年龄更小（P = 0.05），25%的患者其他自身抗体为血清阴性。在首次随访中，基线时抗FHL1阳性的20/33（60%）样本抗FHL1自身抗体转为阴性。开始治疗后抗FHL1自身抗体很少出现。基线时抗FHL1自身抗体水平与肌酸激酶（r = 0.62，P = 0.01）、使用肌炎疾病活动评估工具（MYOACT）测量的疾病活动度（n = 14，P = 0.004）呈正相关，与徒手肌力测试-8（r = -0.59，P = 0.02）呈负相关。
27%的IIM患者存在抗FHL1自身抗体；其中25%的患者其他自身抗体为阴性。其他自身免疫性疾病的频率和水平较低。抗FHL1水平常随免疫抑制治疗而降低，与诊断时的疾病活动度测量相关，开始治疗后很少出现。
