Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis
Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis
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DOI：
10.1371/journal.pone.0121124
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发表时间：
2015-04-08
期刊：
影响因子：
3.7
通讯作者：
Wakao, Hiroshi
中科院分区：
文献类型：
--
作者：
Sugimoto, Chie;Konno, Takahiko;Wakao, Hiroshi
背景纤维肌痛（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疾病，但精神病学、心理学和普通医学认为它是一种综合征 (FMS) 或心身疾病。由于缺乏具体的结构和/或病理证据，患者对 FMS 产生了偏见，认为 FMS 是一种医学上无法解释的症状，意味着不真实。此外，FMS 经常与类风湿性关节炎 (RA) 或脊柱关节炎 (SpA) 并存，两者都有相似的适应症。在这项研究中，从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。方法对患者和健康供体 (HD) 的外周血单核细胞 (PBMC) 进行多色流式细胞术分析。分析PBMC中粘膜相关不变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）。结果与HD相比，FMS、RA和SpA中MAIT细胞群减少。在 MAIT 细胞的细胞表面抗原中，三种趋化因子受体 CCR4、CCR7 和 CXCR1、自然杀伤 (NK) 受体 NKp80、信号淋巴细胞相关分子 (SLAM) 家族 CD150、脱粒标记物 CD107a 和辅助受体 CD8 β 成为 FMS 与 HD 区分的潜在生物标记物。此外，记忆标记 CD44 和炎症趋化因子受体 CXCR1 似乎是 RA 的可能标记，而稳态趋化因子受体 CXCR4 则值得 SpA 与 FMS 的区分。此外，药物治疗中断导致 FMS 中 CCR4、CCR5、CXCR4、CD27、CD28、诱导型共刺激分子 (ICOS)、CD127（IL-7 受体 α）、CD94、NKp80、激活标记物 CD69、整合素家族成员 CD49d 和二肽酶 CD26 的表达发生变化。结论结合目前可用的诊断程序和标准，MAIT 细胞的分析为 FMS、RA 和 SpA 的诊断提供了更客观的标准，这些疾病表现出多方面且令人困惑的相似临床表现。
BackgroundFibromyalgia (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.MethodsPeripheral 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.ResultsThere 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, CD8 beta 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 alpha), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS.ConclusionsCombined 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.