Amlani Adam, Choi May Y, Buhler Katherine A, Hudson Marie, Tarnopolsky Mark, Brady Lauren, Schmeling Heinrike, Swain Mark G, Stingl Cory, Reed Ann, Fritzler Marvin J
Cumming School of Medicine, University of Calgary, Alberta, Canada.
Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
ACR Open Rheumatol. 2023 Jan;5(1):10-14. doi: 10.1002/acr2.11510. Epub 2022 Nov 14.
The rationale for this study was based on reports that valosin-containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti-VCP antibodies in sIBM and other IIMs.
Sera were collected from 73 patients with sIBM and 383 comparators or controls, including patients with IIM (n = 69), those with juvenile dermatomyositis (JDM) (n = 67), those with juvenile idiopathic arthritis (JIA) (n = 47), those with primary biliary cholangitis (PBC) (n = 105), controls that were age matched to patients with sIBM (similarly aged controls [SACs]) (n = 63), and healthy controls (HCs) (n = 32). Immunoglobulin G antibodies to VCP were detected by addressable laser bead immunoassay using a full-length recombinant human protein.
Among patients with sIBM, 26.0% (19/73) were positive for anti-VCP. The frequency in disease controls was 15.0% (48/320). Among SACs, the frequency was 1.6% (1/63), and in HCs 0% (0/32). Frequencies were 17.5% (11/63) for IIM, 25.7% (27/105) for PBC, 3.0% (2/67) for JDM, and 17.0% (8/47) for JIA. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-VCP for sIBM were 26.0%, 87.2%, 28.4%, and 85.9%, respectively. Of patients with sIBM, 15.1% (11/73) were positive for both anti-VCP and anti-cytosolic 5'-nucleotidase 1A (NT5c1A). Eleven percent of patients (8/73) were positive for anti-VCP, but negative for anti-NT5c1A.
Anti-VCP has low sensitivity and moderate specificity for sIBM but may help fill the seronegative gap in sIBM. Further studies are needed to determine whether anti-VCP is a biomarker for a clinical phenotype that may have clinical value.
本研究的理论依据基于以下报道，即遗传性包涵体肌炎（IBM）中发现含缬酪肽蛋白（VCP）突变，且在散发性IBM（sIBM）肌肉活检的镶边空泡中检测到VCP。sIBM或其他炎性肌病（IIM）中尚未报道过抗VCP自身抗体。本研究的目的是确定sIBM和其他IIM中抗VCP抗体的频率及临床意义。
收集了73例sIBM患者以及383例对照者或对照组的血清，包括IIM患者（n = 69）、青少年皮肌炎（JDM）患者（n = 67）、青少年特发性关节炎（JIA）患者（n = 47）、原发性胆汁性胆管炎（PBC）患者（n = 105）、与sIBM患者年龄匹配的对照者（年龄相仿对照者[SACs]）（n = 63）以及健康对照者（HCs）（n = 32）。使用全长重组人蛋白通过可寻址激光珠免疫测定法检测抗VCP的免疫球蛋白G抗体。
在sIBM患者中，26.0%（19/73）抗VCP呈阳性。疾病对照组中的频率为15.0%（48/320）。在SACs中，频率为1.6%（1/63），在HCs中为0%（0/32）。IIM的频率为17.5%（11/63），PBC为25.7%（27/105），JDM为3.0%（2/67），JIA为17.0%（8/47）。抗VCP对sIBM的敏感性、特异性、阳性预测值和阴性预测值分别为26.0%、87.2%、28.4%和85.9%。在sIBM患者中，15.1%（11/73）抗VCP和抗胞质5'-核苷酸酶1A（NT5c1A）均呈阳性。11%的患者（8/73）抗VCP呈阳性，但抗NT5c1A呈阴性。
抗VCP对sIBM的敏感性较低，特异性中等，但可能有助于填补sIBM的血清阴性空白。需要进一步研究以确定抗VCP是否是一种可能具有临床价值的临床表型的生物标志物。
