Sugimoto Chie, Konno Takahiko, Wakao Rika, Fujita Hiroko, Fujita Hiroyoshi, Wakao Hiroshi
Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
Department of Rheumatology, Tokeidai-Memorial Clinic, Sapporo, 060-0031, Japan.
PLoS One. 2015 Apr 8;10(4):e0121124. doi: 10.1371/journal.pone.0121124. eCollection 2015.
Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA.
Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed.
There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.
Combined with the currently available diagnostic procedures and criteria, analysis of MAIT cells offers a more objective standard for the diagnosis of FMS, RA, and SpA, which exhibit multifaceted and confusingly similar clinical manifestations.
纤维肌痛(FM)被定义为一种广泛分布的疼痛。虽然许多风湿病学家和疼痛科医生认为它是一种疼痛性疾病,但精神病学、心理学和普通医学领域则将其视为一种综合征(FMS)或身心障碍。由于缺乏具体的结构和/或病理证据,患者遭受了FMS是一种医学上无法解释的症状的偏见,这意味着其不真实性。此外,FMS常与类风湿性关节炎(RA)或脊柱关节炎(SpA)合并存在,而后两者表现出相似的症状。在本研究中,我们在患者的血液样本中寻找疾病特异性生物标志物,以促进FMS的客观诊断,并将其与RA和SpA区分开来。
对患者和健康供体(HD)的外周血单个核细胞(PBMC)进行多色流式细胞术分析。分析PBMC中黏膜相关恒定T(MAIT)细胞的百分比以及MAIT细胞中细胞表面抗原表达的平均荧光强度(MFI)。
与HD相比,FMS、RA和SpA患者的MAIT细胞数量均减少。在MAIT细胞的细胞表面抗原中,三种趋化因子受体CCR4、CCR7和CXCR1、一种自然杀伤(NK)受体NKp80、一个信号淋巴细胞相关分子(SLAM)家族成员CD150、一个脱颗粒标记物CD107a以及一个共受体CD8β,成为区分FMS与HD的潜在生物标志物。此外,一个记忆标记物CD44和一个炎症趋化因子受体CXCR1似乎是RA的可能标记物,而一个稳态趋化因子受体CXCR4有助于SpA与FMS的区分。此外,药物治疗中断导致FMS患者中CCR4、CCR5、CXCR4、CD27、CD28、诱导性共刺激分子(ICOS)、CD127(IL - 7受体α)、CD94、NKp80、一个活化标记物CD69、一个整合素家族成员CD49d以及一个二肽酶CD26的表达发生改变。
结合目前可用的诊断程序和标准,对MAIT细胞的分析为FMS、RA和SpA的诊断提供了更客观的标准,这三种疾病表现出多方面且令人困惑的相似临床表现。