Department of Medicine, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Autonomous University of Barcelona, Campus de la UAB, Plaça Cívica, 08193 Bellaterra, Barcelona, Spain.
Arthritis Res Ther. 2021 Jul 24;23(1):200. doi: 10.1186/s13075-021-02575-y.
Oxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers.
Consecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1.
Twenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without.
The AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.
氧化脂类是与炎症有关的生物脂质。我们之前发现某些氧化脂类与银屑病关节炎（PsA）患者的临床表现相关。在这里，我们比较了 PsA 患者和无炎症性关节炎的银屑病（PsO）患者的氧化脂类谱，以确定与特定疾病表现相关的氧化脂类，从而更好地了解疾病发病机制并确定新的生物标志物。
连续招募来自风湿病门诊的 PsA（符合 PsA 的 CASPAR 分类标准）和 PsO 患者。进行了全面的临床检查，包括腱附着点（利兹腱附着点指数（LEI））和关节受累（SJC/TJC 66/68）。患者在视觉模拟量表（VAS）上评估疼痛和整体疾病活动度，范围为 0 到 100。随后计算疾病活动评分：cDAPSA（银屑病关节炎疾病活动指数）和银屑病面积和严重程度指数（PASI）。通过质谱法测定血清氧化脂类，并使用 Metaboanalyst 4.0 和 R 版本 3.6.1 分析它们与临床特征（PASI/LEI 和 cDAPSA）的关联。
共纳入 20 例 PsO（平均年龄 52[10.8]，55%为男性）和 19 例 PsA 患者（平均年龄 60.5[11.4]，63.1%为男性）。PsO 患者的平均体重指数（BMI）为 33.7（6.84），平均 PASI 为 3.8（4.2）。PsA 患者的平均 BMI 为 31.9（5.6），TJC 为 9.3（10.41），SJC 为 3.7（4.23），平均 cDAPSA 为 23.3（11.4）。63.1%的 PsA 患者有腱附着点炎（平均 LEI 2.2[3]），相同比例的患者有银屑病（平均 PASI 3[5]）。分析血清氧化脂类水平。PASI 评分较高（>2.5）的 PsO 和 PsA 患者血清中促炎氧化脂类的浓度明显较低，其中大多数是花生四烯酸衍生的（AA）。氧化脂类谱分析与 cDAPSA 无关。有趣的是，几种 AA 衍生的氧化脂类（5,15 二-HETE（5S,15S-二羟基-6E,8Z,10Z,13E-二十碳四烯酸）、5-氧代 ET E（5-氧代二十碳四烯酸）、PGE2（前列腺素 E2）、11bPGE2（11β前列腺素 D2）和 LTB4（白三烯 B4））在有腱附着点炎的 PsA 患者中明显升高，而无腱附着点炎的患者则明显降低。
较高皮肤评分的 PsO 和 PsA 患者中，AA 衍生的促炎氧化脂类含量较低。关节疾病活动度与氧化脂类浓度无关。然而，腱附着点炎与 PsA 患者 AA 衍生的促炎氧化脂类增加有关。需要进一步研究以确定氧化脂类谱是否可以作为 PsA 患者腱附着点炎的良好生物标志物。
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