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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

Effect of the daily drug treatment on MAIT cell frequency in FMS.The percentage of total, CD8+, DN, and CD4+ MAIT cells (Vα7.2+CD161high) within total T cells (CD3+) from the same individuals (n = 9) before and after the drug treatment interruption is shown. The statistical significance and P value were with the Wilcoxon matched-pairs signed rank test. Asterisk shows significance. *: P< 0.05
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pone.0121124.g005: Effect of the daily drug treatment on MAIT cell frequency in FMS.The percentage of total, CD8+, DN, and CD4+ MAIT cells (Vα7.2+CD161high) within total T cells (CD3+) from the same individuals (n = 9) before and after the drug treatment interruption is shown. The statistical significance and P value were with the Wilcoxon matched-pairs signed rank test. Asterisk shows significance. *: P< 0.05

Mentions: We then assessed whether the daily drug intake affected the frequency of MAIT cell subsets and the expression of the cell surface molecules in MAIT cells from FMS, as patients were ongoing treatment when the above analysis was performed (Table 4). After 48 h of the drug treatment interruption, CD8+ MAIT cells have increased, while little change in CD4+, DN, and total MAIT cell frequency was observed, implying that CD8+ MAIT cells were particularly sensitive to the drugs and would tightly be linked with the morbidity of FMS (Fig. 5 and S5 Table). Such an interruption also engendered an increase of CCR4 in DN MAIT cells and of CCR5 in total MAIT cells, while CXCR4 expression has declined in total and CD8+ MAIT cells (Fig. 6 and S6 Table). Given that CCR4 and CCR5 are receptors for the inflammatory chemokines such as CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, and CCL11, such an increase indicated that the morbidity of FMS comprises, in part, inflammation [20,21]. Interruption of the drug treatment enhanced CD27 level in CD8+ MAIT cells (Fig. 6 and S6 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)

Effect of the daily drug treatment on MAIT cell frequency in FMS.The percentage of total, CD8+, DN, and CD4+ MAIT cells (Vα7.2+CD161high) within total T cells (CD3+) from the same individuals (n = 9) before and after the drug treatment interruption is shown. The statistical significance and P value were with the Wilcoxon matched-pairs signed rank test. Asterisk shows significance. *: P< 0.05
© Copyright Policy
Related In: Results  -  Collection

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

pone.0121124.g005: Effect of the daily drug treatment on MAIT cell frequency in FMS.The percentage of total, CD8+, DN, and CD4+ MAIT cells (Vα7.2+CD161high) within total T cells (CD3+) from the same individuals (n = 9) before and after the drug treatment interruption is shown. The statistical significance and P value were with the Wilcoxon matched-pairs signed rank test. Asterisk shows significance. *: P< 0.05
Mentions: We then assessed whether the daily drug intake affected the frequency of MAIT cell subsets and the expression of the cell surface molecules in MAIT cells from FMS, as patients were ongoing treatment when the above analysis was performed (Table 4). After 48 h of the drug treatment interruption, CD8+ MAIT cells have increased, while little change in CD4+, DN, and total MAIT cell frequency was observed, implying that CD8+ MAIT cells were particularly sensitive to the drugs and would tightly be linked with the morbidity of FMS (Fig. 5 and S5 Table). Such an interruption also engendered an increase of CCR4 in DN MAIT cells and of CCR5 in total MAIT cells, while CXCR4 expression has declined in total and CD8+ MAIT cells (Fig. 6 and S6 Table). Given that CCR4 and CCR5 are receptors for the inflammatory chemokines such as CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, and CCL11, such an increase indicated that the morbidity of FMS comprises, in part, inflammation [20,21]. Interruption of the drug treatment enhanced CD27 level in CD8+ MAIT cells (Fig. 6 and S6 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