Pérez Vertti Valdés Melina, Jüngel Astrid, Bitterli Pamela, Devan Jan, Rehrauer Hubert, Opitz Lennart, Sirucek Laura, Schweinhardt Petra, Catanzaro Sabrina, Distler Oliver, Brunner Florian, Dudli Stefan
Center of Experimental Rheumatology, Balgrist Campus, University Hospital Zurich, University of Zurich, Lengghalde 8, 8008, Zurich, Switzerland.
Department of Physical Medicine and Rheumatology, Balgrist University Hospital, University of Zurich, Zurich, Switzerland.
Mol Med. 2025 Mar 12;31(1):94. doi: 10.1186/s10020-025-01148-y.
Patients with Complex Regional Pain Syndrome (CRPS) present prolonged, debilitating pain and functional impairment. Treatments are not disease-modifying due to the poorly understood underlying pathomechanisms. This study aimed to identify the molecular signatures of potential CRPS type 1 subgroups.
Twelve women with CRPS type 1 were included. Demographics and pain questionnaires were recorded. Skin biopsies of the affected and non-affected limbs (n = 6 + 6) and peripheral blood (n = 11) were collected. RNA sequencing was performed on skin and peripheral blood mononuclear cells (PBMCs). Twenty cytokines were quantified in blood plasma (n = 12).
Cluster analysis of the affected skin identified two CRPS subgroups (SG). SG1 exhibited increased gene expression related to epidermal development, metabolic processes, and a greater abundance of keratinocytes. SG2 showed enhanced transcriptomic changes in inflammatory, immune, and fibrotic processes, along with higher abundance of fibroblasts, macrophages, and endothelial cells. PBMCs transcriptomics revealed the same SG1/SG2 clusters and highlighted a stronger inflammatory response in the blood of SG1, suggesting distinct tissue-specific immune responses for the subgroups. Interleukin-1 receptor antagonist (IL-1RA) levels were higher in the blood plasma of SG1 (FDR = 0.01), consistent with its encoding gene IL1RN expression in PBMCs (log2 FC = 1.10, P < 0.001) and affected skin (log2 FC = 0.88, P = 0.006). Subgroups did not differ in demographic or clinical parameters but correlations among clinical factors varied between them.
This study identified two potential biological subgroups of CRPS type 1 in women through skin and blood transcriptomic profiling, advancing the understanding of this condition. This could facilitate the development of targeted treatments for CRPS type 1.
复杂性区域疼痛综合征（CRPS）患者存在长期的、使人衰弱的疼痛和功能障碍。由于潜在的病理机制尚不清楚，目前的治疗方法无法改变疾病进程。本研究旨在确定1型CRPS潜在亚组的分子特征。
纳入12名1型CRPS女性患者。记录人口统计学和疼痛问卷信息。采集患侧和非患侧肢体的皮肤活检样本（n = 6 + 6）以及外周血样本（n = 11）。对皮肤和外周血单个核细胞（PBMC）进行RNA测序。对12份血浆样本中的20种细胞因子进行定量分析。
对患侧皮肤进行聚类分析，确定了两个CRPS亚组（SG）。SG1表现出与表皮发育、代谢过程相关的基因表达增加，角质形成细胞数量更多。SG2在炎症、免疫和纤维化过程中表现出更强的转录组变化，同时成纤维细胞、巨噬细胞和内皮细胞数量更多。PBMC转录组学显示出相同的SG1/SG2聚类，并突出了SG1血液中更强的炎症反应，表明这两个亚组存在不同的组织特异性免疫反应。SG1血浆中白细胞介素-1受体拮抗剂（IL-1RA）水平较高（FDR = 0.01），与其在PBMC中的编码基因IL1RN表达一致（log2 FC = 1.10，P < 0.001），在患侧皮肤中也有表达（log2 FC = 0.88，P = 0.006）。亚组在人口统计学或临床参数上没有差异，但临床因素之间的相关性在亚组间有所不同。
本研究通过皮肤和血液转录组分析，在女性中确定了两个1型CRPS潜在生物学亚组，增进了对该疾病的理解。这可能有助于开发针对1型CRPS的靶向治疗方法。
