Department of Internal Medicine I, José Carreras Center for Immuno- and Gene Therapy, Saarland University Medical School, Homburg/Saar, Germany.
Outpatient Rheumatology Center Berlin-Lichtenberg, Berlin, Germany.
Clin Exp Rheumatol. 2020 Jan-Feb;38(1):94-98. Epub 2019 May 10.
Previously we discovered antibodies against progranulin (PGRN-abs) in a protein array-based screening of sera from various rheumatic diseases. Here we conducted a study to evaluate the prevalence of PGRN-abs in seropositive and seronegative rheumatoid arthritis (RA).
PGRN-abs were determined in the sera from 257 RA patients being seropositive for RF-IgM and/or ACPA-IgG and from 224 seronegative RA patients who were prospectively included in this study (total RA cohort n=481). All serum samples from the included participants were tested for RF-IgM as well as for ACPA-IgG, and PGRN-abs were determined using a previously described ELISA. Statistics was performed using the χ2 test for evaluating differences in clinical data; to evaluate independent statistical effects on the frequency of PGRN-abs status a logistic regression model with Wald-test was performed.
PGRN-abs were detected in 25.3% from seropositive RA and in 21.0% from RF- and ACPA-negative RA resulting in a prevalence of 23.7% for both cohorts together. Comparing mean DAS28 values in the PGRN-abs positive cohort with the PGRN-abs negative cohort, the DAS28 value was significantly higher in PGRN-abs positive RA patients (3.81 vs. 3.50, p=0.038). A trend for higher frequencies of PGRN-abs in sera of RA patients with unfavourable characteristics such as erosive disease or requiring TNFi medication was observed.
These data suggest that the determination of PGRN-abs in seronegative RA patients may reduce their seronegative status. Further studies are required to evaluate PGRN-abs as a potential diagnostic marker in RA.
我们之前在一项基于蛋白质芯片的多种风湿性疾病血清学筛查中发现了针对颗粒体蛋白前体（PGRN-abs）的抗体。在此，我们进行了一项研究，以评估血清阳性和血清阴性类风湿关节炎（RA）患者中 PGRN-abs 的患病率。
在这项前瞻性研究中，我们检测了 257 例 RF-IgM 和/或 ACPA-IgG 血清阳性 RA 患者和 224 例血清阴性 RA 患者（总 RA 队列 n=481）血清中的 PGRN-abs。所有纳入患者的血清样本均进行 RF-IgM 和 ACPA-IgG 检测，使用之前描述的 ELISA 检测 PGRN-abs。采用卡方检验评估临床数据的差异；采用 Wald 检验的 logistic 回归模型评估独立因素对 PGRN-abs 状态频率的影响。
在血清阳性 RA 患者中，PGRN-abs 的检出率为 25.3%，在 RF 和 ACPA 阴性 RA 患者中为 21.0%，两组的总检出率为 23.7%。在 PGRN-abs 阳性组和 PGRN-abs 阴性组中比较 DAS28 均值，PGRN-abs 阳性 RA 患者的 DAS28 值明显更高（3.81 比 3.50，p=0.038）。在具有侵蚀性疾病或需要 TNFi 治疗等不良特征的 RA 患者中，PGRN-abs 血清阳性率呈升高趋势。
这些数据表明，在血清阴性 RA 患者中检测 PGRN-abs 可能会降低其血清阴性状态。需要进一步研究来评估 PGRN-abs 作为 RA 的潜在诊断标志物。
