早期中轴型脊柱关节炎患者两独立队列中针对三个新肽的抗体。
Antibodies Against Three Novel Peptides in Early Axial Spondyloarthritis Patients From Two Independent Cohorts.
机构信息
UH, Hasselt, Belgium.
UH, Hasselt, Belgium and ReumaClinic, Genk, Belgium, and Maastricht University Medical Center, Maastricht, The Netherlands.
出版信息
Arthritis Rheumatol. 2020 Dec;72(12):2094-2105. doi: 10.1002/art.41427. Epub 2020 Nov 4.
OBJECTIVE
This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts.
METHODS
An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH-axSpA) was determined by enzyme-linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort.
RESULTS
We identified antibodies to 9 novel UH-axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH-axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH-axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C-reactive protein. Testing for antibodies to these 3 UH-axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%.
CONCLUSION
Antibodies to 3 UH-axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.
目的
本研究旨在鉴定出轴性脊柱关节炎（SpA）中的新型自身抗体，并确定其在来自两个独立队列的早期轴性 SpA 患者和对照者中的诊断潜力。
方法
使用轴性 SpA 互补 DNA 噬菌体展示文库来筛选来自早期轴性 SpA 患者的血浆中的新型 IgG 抗体。通过酶联免疫吸附试验，在 76 例早期轴性 SpA 患者、75 例非特异性慢性下腰痛对照者、60 例类风湿关节炎患者和 94 例来自 Hasselt 大学的 UH 队列的健康对照者中，确定这些针对新型肽的抗体的存在（即，在 UH-axSpA 队列中鉴定出的肽）。在来自鲁汶大学医院（Bio）SPAR（脊柱关节炎[生物制剂]）队列的 174 例轴性 SpA 患者（其中 79 例为早期轴性 SpA）中进一步验证了这些新型肽的抗体反应性。
结果
我们鉴定出针对 9 种新型 UH-axSpA 肽的抗体，这些肽对应于随机形成的肽和一种新型轴性 SpA 自身抗原双同源盒蛋白 4。针对对轴性 SpA 诊断具有最高阳性似然比（LR）的 3 种 UH-axSpA 肽的抗体，在来自 UH 和（Bio）SPAR 队列的早期轴性 SpA 患者中明显更为常见（14.2%[22/155]），而非慢性下腰痛对照者（5%[4/75]），特异性为 95%。使用针对这 3 种 UH-axSpA 肽的抗体确认轴性 SpA 的阳性 LR 为 2.7，高于当前使用的实验室标志物 C 反应蛋白的 LR。在慢性下腰痛患者中检测针对这 3 种 UH-axSpA 肽的抗体可将轴性 SpA 诊断的后验概率从 79%提高到 91%。
结论
针对 3 种 UH-axSpA 肽的抗体可能为诊断亚组轴性 SpA 患者提供一种新的工具。
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