Kuret Tadeja, Frank-Bertoncelj Mojca, Lakota Katja, Žigon Polona, Thallinger Gerhard G, Kopitar Andreja N, Čučnik Saša, Tomšič Matija, Hočevar Alojzija, Sodin-Šemrl Snežna
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Front Med (Lausanne). 2022 Jan 20;8:827095. doi: 10.3389/fmed.2021.827095. eCollection 2021.
In the present study, we longitudinally monitored leukocyte subsets, expression of neutrophil surface adhesion molecules (CD62L and CD11b) and serum analytes in therapy-naïve patients with active giant cell arteritis (GCA). We collected blood samples at the baseline, and at weeks 1, 4, 12, 24, and 48 of follow-up, and evaluated short- and long-term effects of glucocorticoids (GC) vs. GC and leflunomide. Our aim was to identify candidate biomarkers that could be used to monitor disease activity and predict an increased risk of a relapse. Following high doses of GC, the numbers of CD4+ T-lymphocytes and B-lymphocytes transiently increased and then subsided when GC dose tapering started at week 4. In contrast, the numbers of neutrophils significantly increased during the follow-up time of 12 weeks compared to pre-treatment time. Neutrophil CD62L rapidly diminished after initiation of GC therapy, however its expression remained low at week 48, only in patients under combinatorial therapy with leflunomide. Levels of acute phase reactant SAA and IL-6 decreased significantly after treatment with GC and leflunomide, while levels of IL-8, IL-18, and CHI3L1 did not change significantly during the follow-up period. CHI3L1 was associated with signs of transmural inflammation and vessel occlusion and might therefore serve as a marker of fully developed active GCA, and a promising therapeutic target. Patients with relapses had higher levels of IL-23 at presentation than patients without relapses ( = 0.021). Additionally, the levels of IL-23 were higher at the time of relapse compared to the last follow-up point before relapse. IL-23 might present a promising biomarker of uncontrolled and active disease and could give early indication of upcoming relapses.
在本研究中，我们对初治的活动性巨细胞动脉炎（GCA）患者的白细胞亚群、中性粒细胞表面黏附分子（CD62L和CD11b）的表达以及血清分析物进行了纵向监测。我们在基线时以及随访的第1、4、12、24和48周采集血样，并评估了糖皮质激素（GC）与GC联合来氟米特的短期和长期效果。我们的目的是确定可用于监测疾病活动和预测复发风险增加的候选生物标志物。在给予高剂量GC后，CD4⁺T淋巴细胞和B淋巴细胞数量短暂增加，然后在第4周开始逐渐减少GC剂量时下降。相比之下，与治疗前相比，中性粒细胞数量在12周的随访期内显著增加。GC治疗开始后，中性粒细胞CD62L迅速减少，然而仅在接受来氟米特联合治疗的患者中，其在第48周时的表达仍较低。急性期反应物SAA和IL-6水平在接受GC和来氟米特治疗后显著下降，而IL-8、IL-18和CHI3L1水平在随访期间没有显著变化。CHI3L1与透壁炎症和血管闭塞的体征相关，因此可能作为完全发展的活动性GCA的标志物以及一个有前景的治疗靶点。复发患者在就诊时的IL-23水平高于未复发患者（P = 0.021）。此外，与复发前的最后一个随访点相比，复发时IL-23水平更高。IL-23可能是未控制的活动性疾病的一个有前景的生物标志物，并可提前提示即将复发。
