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Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Comparison of the cell surface antigen expression level in MAIT cells between HD and FMS.A, Chemokine receptor expression in total, CD8+, and DN MAIT cells. B, Co-stimulatory molecule expression in total, CD8+, and DN MAIT cells. C, Cytokine receptor expression in total, CD8+, and DN MAIT cells. D, SLAM family, memory, and activation marker expression in total, CD8+, and DN MAIT cells. E, NK receptor expression in total, CD8+, and DN MAIT cells. F, CD95 (Fas) expression in total, CD8+, and DN MAIT cells. G, Integrin family expression in total, CD8+, and DN MAIT cells. H, Miscellaneous molecule expression in total, CD8+, and DN MAIT cells. A-H. MFI is shown with median. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pair exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (the nonparametric Mann-Whitney U test)
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pone.0121124.g002: Comparison of the cell surface antigen expression level in MAIT cells between HD and FMS.A, Chemokine receptor expression in total, CD8+, and DN MAIT cells. B, Co-stimulatory molecule expression in total, CD8+, and DN MAIT cells. C, Cytokine receptor expression in total, CD8+, and DN MAIT cells. D, SLAM family, memory, and activation marker expression in total, CD8+, and DN MAIT cells. E, NK receptor expression in total, CD8+, and DN MAIT cells. F, CD95 (Fas) expression in total, CD8+, and DN MAIT cells. G, Integrin family expression in total, CD8+, and DN MAIT cells. H, Miscellaneous molecule expression in total, CD8+, and DN MAIT cells. A-H. MFI is shown with median. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pair exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (the nonparametric Mann-Whitney U test)

Mentions: We sought the cell surface antigens in MAIT cells that allowed the distinction between HD and FMS. In FMS, we found a significant increase of CCR7, a chemokine receptor required for lymph node homing, in total MAIT cells and in CD8+ MAIT cells and of CD27, a costimulatory molecule for T cell activation, in DN MAIT cells, compared with HD (Fig. 2 and Table 2 and S3 Table). In contrast, there was a decrease in two chemokine receptors, CCR4, CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, and a coreceptor, CD8β in all subsets of MAIT cells, while a decrease in CD244, another SLAM family member, in total and CD8+ MAIT cells, CD69, an activation marker, in total MAIT cells, and CD107a in DN MAIT cells, was seen compared with HD (Fig. 2 and Table 2 and S3 Table).


Mucosal-associated invariant T cell is a potential marker to distinguish fibromyalgia syndrome from arthritis.

Sugimoto C, Konno T, Wakao R, Fujita H, Fujita H, Wakao H - PLoS ONE (2015)

Comparison of the cell surface antigen expression level in MAIT cells between HD and FMS.A, Chemokine receptor expression in total, CD8+, and DN MAIT cells. B, Co-stimulatory molecule expression in total, CD8+, and DN MAIT cells. C, Cytokine receptor expression in total, CD8+, and DN MAIT cells. D, SLAM family, memory, and activation marker expression in total, CD8+, and DN MAIT cells. E, NK receptor expression in total, CD8+, and DN MAIT cells. F, CD95 (Fas) expression in total, CD8+, and DN MAIT cells. G, Integrin family expression in total, CD8+, and DN MAIT cells. H, Miscellaneous molecule expression in total, CD8+, and DN MAIT cells. A-H. MFI is shown with median. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pair exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (the nonparametric Mann-Whitney U test)
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4390316&req=5

pone.0121124.g002: Comparison of the cell surface antigen expression level in MAIT cells between HD and FMS.A, Chemokine receptor expression in total, CD8+, and DN MAIT cells. B, Co-stimulatory molecule expression in total, CD8+, and DN MAIT cells. C, Cytokine receptor expression in total, CD8+, and DN MAIT cells. D, SLAM family, memory, and activation marker expression in total, CD8+, and DN MAIT cells. E, NK receptor expression in total, CD8+, and DN MAIT cells. F, CD95 (Fas) expression in total, CD8+, and DN MAIT cells. G, Integrin family expression in total, CD8+, and DN MAIT cells. H, Miscellaneous molecule expression in total, CD8+, and DN MAIT cells. A-H. MFI is shown with median. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. Asterisk shows the group-pair exhibiting significance. *: P< 0.05, **: P < 0.01, ***: P<0.001 (the nonparametric Mann-Whitney U test)
Mentions: We sought the cell surface antigens in MAIT cells that allowed the distinction between HD and FMS. In FMS, we found a significant increase of CCR7, a chemokine receptor required for lymph node homing, in total MAIT cells and in CD8+ MAIT cells and of CD27, a costimulatory molecule for T cell activation, in DN MAIT cells, compared with HD (Fig. 2 and Table 2 and S3 Table). In contrast, there was a decrease in two chemokine receptors, CCR4, CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, and a coreceptor, CD8β in all subsets of MAIT cells, while a decrease in CD244, another SLAM family member, in total and CD8+ MAIT cells, CD69, an activation marker, in total MAIT cells, and CD107a in DN MAIT cells, was seen compared with HD (Fig. 2 and Table 2 and S3 Table).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Hygiene & Cellular Preventive Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.

ABSTRACT

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus