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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

Potential biomarkers distinguishing HD, FMS, RA and SpA.MFI is shown with median for the indicated cell surface antigen. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. The number in figure shows a P value after the Kruskal-Wallis test. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***:P<0.001 (P value adjusted with the Dunn's multicomponent test). total: total MAIT cells; CD8+; CD8+ MAIT cells; DN: DN MAIT cells.
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pone.0121124.g003: Potential biomarkers distinguishing HD, FMS, RA and SpA.MFI is shown with median for the indicated cell surface antigen. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. The number in figure shows a P value after the Kruskal-Wallis test. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***:P<0.001 (P value adjusted with the Dunn's multicomponent test). total: total MAIT cells; CD8+; CD8+ MAIT cells; DN: DN MAIT cells.

Mentions: Next we tried to find out the cell surface antigens in MAIT cells that could differentiate HD, FMS, RA, and SpA. Kruskal-Wallis test has revealed that CCR4, CCR7, CXCR1, CXCR4, CD94, NKp80, CD150, CD44, CD8β, and CD107a are possible makers to distinguish the three diseases (Table 3, Kruskal-Wallis test). Multiple comparisons after P value adjustment have allowed the identification of CCR4, CCR7, CXCR1, NKp80, CD150, CD8β and CD107a to be potential primary markers for FMS to distinguish from HD, RA and SpA (Fig. 3 and Table 3, Adjusted P values). In addition, CXCR1 in DN MAIT cells and CD44 in total MAIT cells may serve as auxiliary markers to differentiate FMS from RA (Fig. 3 and Table 3 and S3 Table). CXCR4 appeared to be a marker to distinguish SpA from HD in total MAIT cells, and also be useful to discern FMS and SpA in total and DN MAIT cells (Fig. 3 and Table 3 and S3 Table). Among the cell surface molecules so far studied, CD94 in total and DN MAIT cells, and CXCR1 in DN MAIT cells, would allow the distinction between RA and SpA (Fig. 3 and Table 3 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)

Potential biomarkers distinguishing HD, FMS, RA and SpA.MFI is shown with median for the indicated cell surface antigen. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. The number in figure shows a P value after the Kruskal-Wallis test. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***:P<0.001 (P value adjusted with the Dunn's multicomponent test). total: total MAIT cells; CD8+; CD8+ MAIT cells; DN: DN MAIT cells.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4390316&req=5

pone.0121124.g003: Potential biomarkers distinguishing HD, FMS, RA and SpA.MFI is shown with median for the indicated cell surface antigen. The dotted line indicates MFI for the isotype control. Horizontal line: Median; boxes: 25th percentile and 75th percentile; whiskers: Minimum and Maximum. The number in figure shows a P value after the Kruskal-Wallis test. Asterisk shows the group-pairs exhibiting significance. *: P< 0.05, **: P < 0.01, ***:P<0.001 (P value adjusted with the Dunn's multicomponent test). total: total MAIT cells; CD8+; CD8+ MAIT cells; DN: DN MAIT cells.
Mentions: Next we tried to find out the cell surface antigens in MAIT cells that could differentiate HD, FMS, RA, and SpA. Kruskal-Wallis test has revealed that CCR4, CCR7, CXCR1, CXCR4, CD94, NKp80, CD150, CD44, CD8β, and CD107a are possible makers to distinguish the three diseases (Table 3, Kruskal-Wallis test). Multiple comparisons after P value adjustment have allowed the identification of CCR4, CCR7, CXCR1, NKp80, CD150, CD8β and CD107a to be potential primary markers for FMS to distinguish from HD, RA and SpA (Fig. 3 and Table 3, Adjusted P values). In addition, CXCR1 in DN MAIT cells and CD44 in total MAIT cells may serve as auxiliary markers to differentiate FMS from RA (Fig. 3 and Table 3 and S3 Table). CXCR4 appeared to be a marker to distinguish SpA from HD in total MAIT cells, and also be useful to discern FMS and SpA in total and DN MAIT cells (Fig. 3 and Table 3 and S3 Table). Among the cell surface molecules so far studied, CD94 in total and DN MAIT cells, and CXCR1 in DN MAIT cells, would allow the distinction between RA and SpA (Fig. 3 and Table 3 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