Kaczmarczyk Bartosz, Conde Carmen, Gonzalez Antonio
Experimental and Observational Rheumatology and Rheumatology Unit, Instituto Investigacion Sanitaria-Hospital Clinico Universitario de Santiago, Travesia Choupana, sn, Santiago de Compostela, 15706-A Coruña, Spain.
Arthritis Res Ther. 2025 Jul 19;27(1):151. doi: 10.1186/s13075-025-03617-5.
We need screening for RA patients at high risk of RA-ILD to prevent the associated decrease in life quality and survival. The proposed screenings disagree regarding the anti-citrullinated protein antibodies (ACPA) because of their inconsistent association across recent studies. Therefore, we hypothesized that meta-analysis of the published reports should reveal clues explaining the heterogeneity of results, helping us progress in RA-ILD early detection.
We aimed to discover the factors accounting for the variability of the ACPA association in the published reports.
We searched the Web of Science and PubMed databases for studies reporting ACPA in RA-ILD and RA-control groups. The identified studies were analyzed using meta-analysis and meta-regression to identify moderators of the ACPA association.
We found 513 unique records, containing 31 eligible data sets. The meta-analysis preceding the search for moderators showed a remarkable heterogeneity (p = 5.7 × 10). Appropriate tests showed that it was largely attributable (58.1%) to an outlier study, which had recruited cases and controls in different place and time contexts. The exclusion of this outlier from subsequent analyses did not completely remove heterogeneity (p = 0.004). However, it permitted the identification of the patient classification method as a significant moderator: The 14 studies using chest CT showed stronger ACPA association with RA-ILD (OR = 3.05 [95%CI: 2.12-4.38]) than the 16 employing multifactorial criteria (1.55 [95%CI: 1.18-2.03]; p = 0.0047 for the contrast). This moderator accounted for the significant heterogeneity (p = 0.079), was robust in sensitivity analyses, and was the only one found.
Our results validate the ACPA association with RA-ILD, reinforce the importance of study design, and suggest the need to consider if studies relying on chest CT for classification could be more fruitful in the search for RA-ILD biomarkers.
我们需要对有类风湿关节炎相关间质性肺病（RA-ILD）高风险的类风湿关节炎（RA）患者进行筛查，以防止生活质量下降和生存率降低。由于近期研究中抗瓜氨酸化蛋白抗体（ACPA）的关联不一致，目前提议的筛查方法存在分歧。因此，我们假设对已发表报告进行荟萃分析应能揭示解释结果异质性的线索，帮助我们在RA-ILD早期检测方面取得进展。
我们旨在发现已发表报告中ACPA关联变异性的影响因素。
我们在科学网和PubMed数据库中搜索报告RA-ILD组和RA对照组中ACPA的研究。使用荟萃分析和荟萃回归对纳入的研究进行分析，以确定ACPA关联的调节因素。
我们找到513条独特记录，包含31个合格数据集。在寻找调节因素之前进行的荟萃分析显示出显著的异质性（p = 5.7×10）。适当的检验表明，这在很大程度上（58.1%）归因于一项异常值研究，该研究在不同地点和时间背景下招募病例和对照。在后续分析中排除该异常值并未完全消除异质性（p = 0.004）。然而，这使得能够将患者分类方法确定为一个显著的调节因素：14项使用胸部CT的研究显示ACPA与RA-ILD的关联更强（OR = 3.05 [95%CI：2.12 - 4.38]），而16项采用多因素标准的研究中该关联为1.55 [95%CI：1.18 - 2.03]；两者对比p = 0.0047）。该调节因素解释了显著的异质性（p = 0.079），在敏感性分析中具有稳健性，且是唯一发现的调节因素。
我们的结果验证了ACPA与RA-ILD的关联，强化了研究设计的重要性，并表明有必要考虑依赖胸部CT进行分类的研究在寻找RA-ILD生物标志物方面是否可能更有成效。
