Venerito V, Natuzzi D, Bizzoca R, Lacarpia N, Cacciapaglia F, Lopalco G, Iannone F
Rheumatology Unit, Department of Emergency and Organ Transplantations, University of Bari 'Aldo Moro', Bari, Italy.
Clin Exp Immunol. 2020 Aug;201(2):200-204. doi: 10.1111/cei.13451. Epub 2020 May 27.
The pathogenesis of psoriatic arthritis (PsA) involves several pathways, including the CD40/CD40L signaling which promotes the release of multiple cytokines. Transmembrane CD40L is also released in soluble form (sCD40L) and phosphodiesterase 4 (PDE4) seems to be involved in its cleavage. We aimed to investigate whether apremilast, a PDE4 inhibitor, could modify circulating levels of sCD40L in PsA patients, and the possible associations of these changes with clinical response. Consecutive PsA patients starting apremilast in routine clinical practice were prospectively observed. Disease Activity of Psoriatic Arthritis (DAPSA), Psoriasis Area Severity Index (PASI), Leeds Enthesitis Score (LEI) and serum samples were collected at baseline and at 6 months. Samples were run in a Bio-Plex ProTM plate for sCD40L. To investigate the association of sCD40L level with DAPSA based minor response, low disease activity (LDA) and/or remission at 6 months of treatment, multivariate logistic regression models with backward selection (P < 0·05) were built. We studied 27 patients (16 of 27 women, 59·6%) with PsA and mean age [± standard deviation (s.d.)] of 58·4 ± 10 years. A significant reduction of the mean values of DAPSA, LEI and PASI was detected at 6 months. Mean serum levels of sCD40L decreased from baseline 5364 ± 2025 pg/ml to 4412 ± 2629 at 6 months (P = 0·01). Baseline DAPSA [odds ratio (OR) = 0·80, 95% confidence interval (CI) = 0·65-0·98] and sCD40L (OR = 1·001, 95% CI = 1·0001-1·0027) were independently associated with DAPSA LDA/remission at 6 months. In PsA patients, sCD40L levels decrease upon apremilast treatment and might predict short-term clinical response to apremilast.
银屑病关节炎（PsA）的发病机制涉及多种途径，包括促进多种细胞因子释放的CD40/CD40L信号通路。跨膜CD40L也以可溶性形式（sCD40L）释放，磷酸二酯酶4（PDE4）似乎参与其裂解过程。我们旨在研究磷酸二酯酶4抑制剂阿普斯特是否能改变PsA患者循环中sCD40L的水平，以及这些变化与临床反应之间可能存在的关联。对在常规临床实践中开始使用阿普斯特的连续性PsA患者进行前瞻性观察。在基线期和6个月时收集银屑病关节炎疾病活动度（DAPSA）、银屑病面积和严重程度指数（PASI）、利兹附着点炎评分（LEI）以及血清样本。样本在Bio-Plex ProTM板上检测sCD40L。为了研究sCD40L水平与治疗6个月时基于DAPSA的微小反应、低疾病活动度（LDA）和/或缓解之间的关联，构建了采用向后选择法（P < 0·05）的多因素逻辑回归模型。我们研究了27例PsA患者（27例中有16例女性，占59·6%），平均年龄为58·4 ± 10岁。在6个月时检测到DAPSA、LEI和PASI的平均值显著降低。sCD40L的平均血清水平从基线时的5364 ± 2025 pg/ml降至6个月时的4412 ± 2629 pg/ml（P = 0·01）。基线DAPSA [比值比（OR）= 0·80，95%置信区间（CI）= 0·65 - 0·98]和sCD40L（OR = 1·001，95% CI = 1·0001 - 1·0027）与治疗6个月时的DAPSA低疾病活动度/缓解独立相关。在PsA患者中，阿普斯特治疗后sCD40L水平降低，且可能预测对阿普斯特的短期临床反应。
